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Erschienen in: Neurotoxicity Research 3/2013

01.04.2013 | Review

Melatonin Antioxidative Defense: Therapeutical Implications for Aging and Neurodegenerative Processes

verfasst von: Seithikurippu R. Pandi-Perumal, Ahmed S. BaHammam, Gregory M. Brown, D. Warren Spence, Vijay K. Bharti, Charanjit Kaur, Rüdiger Hardeland, Daniel P. Cardinali

Erschienen in: Neurotoxicity Research | Ausgabe 3/2013

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Abstract

The pineal product melatonin has remarkable antioxidant properties. It is secreted during darkness and plays a key role in various physiological responses including regulation of circadian rhythms, sleep homeostasis, retinal neuromodulation, and vasomotor responses. It scavenges hydroxyl, carbonate, and various organic radicals as well as a number of reactive nitrogen species. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and glutathione reductase, and by augmenting glutathione levels. Melatonin preserves mitochondrial homeostasis, reduces free radical generation and protects mitochondrial ATP synthesis by stimulating Complexes I and IV activities. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases. The efficacy of melatonin in preventing oxidative damage in either cultured neuronal cells or in the brains of animals treated with various neurotoxic agents, suggests that melatonin has a potential therapeutic value as a neuroprotective drug in treatment of Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), stroke, and brain trauma. Therapeutic trials with melatonin indicate that it has a potential therapeutic value as a neuroprotective drug in treatment of AD, ALS, and HD. In the case of other neurological conditions, like PD, the evidence is less compelling. Melatonin’s efficacy in combating free radical damage in the brain suggests that it can be a valuable therapeutic agent in the treatment of cerebral edema following traumatic brain injury or stroke. Clinical trials employing melatonin doses in the range of 50–100 mg/day are warranted before its relative merits as a neuroprotective agent is definitively established.
Literatur
Zurück zum Zitat Acuña-Castroviejo D, Coto-Montes A, Gaia MM, Ortiz GG, Reiter RJ (1997) Melatonin is protective against MPTP-induced striatal and hippocampal lesions. Life Sci 60:L23–L29 Acuña-Castroviejo D, Coto-Montes A, Gaia MM, Ortiz GG, Reiter RJ (1997) Melatonin is protective against MPTP-induced striatal and hippocampal lesions. Life Sci 60:L23–L29
Zurück zum Zitat Acuña-Castroviejo CD, Escames G, Carazo A, León J, Khaldy H, Reiter RJ (2002) Melatonin, mitochondrial homeostasis and mitochondrial-related diseases. Curr Top Med Chem 2:133–151 Acuña-Castroviejo CD, Escames G, Carazo A, León J, Khaldy H, Reiter RJ (2002) Melatonin, mitochondrial homeostasis and mitochondrial-related diseases. Curr Top Med Chem 2:133–151
Zurück zum Zitat Acuña-Castroviejo CD, Lopez LC, Escames G, Lopez A, García JA, Reiter RJ (2011) Melatonin-mitochondria interplay in health and disease. Curr Top Med Chem 11:221–240 Acuña-Castroviejo CD, Lopez LC, Escames G, Lopez A, García JA, Reiter RJ (2011) Melatonin-mitochondria interplay in health and disease. Curr Top Med Chem 11:221–240
Zurück zum Zitat Adi N, Mash DC, Ali Y, Singer C, Shehadeh L, Papapetropoulos S (2010) Melatonin MT1 and MT2 receptor expression in Parkinson’s disease. Med Sci Monit 16:61–67 Adi N, Mash DC, Ali Y, Singer C, Shehadeh L, Papapetropoulos S (2010) Melatonin MT1 and MT2 receptor expression in Parkinson’s disease. Med Sci Monit 16:61–67
Zurück zum Zitat Alam ZI, Jenner A, Daniel SE, Lees AJ, Cairns N, Marsden CD, Jenner P, Halliwell B (1997) Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J Neurochem 69:1196–1203 Alam ZI, Jenner A, Daniel SE, Lees AJ, Cairns N, Marsden CD, Jenner P, Halliwell B (1997) Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J Neurochem 69:1196–1203
Zurück zum Zitat Alders J, Smits M, Kremer B, Naarding P (2009) The role of melatonin in sleep disturbances in end-stage Huntington’s disease. J Neuropsychiatry Clin Neurosci 21:226–227 Alders J, Smits M, Kremer B, Naarding P (2009) The role of melatonin in sleep disturbances in end-stage Huntington’s disease. J Neuropsychiatry Clin Neurosci 21:226–227
Zurück zum Zitat Aliev G, Li Y, Palacios HH, Obrenovich ME (2011) Oxidative stress induced mitochondrial DNA deletion as a hallmark for the drug development in the context of the cerebrovascular diseases. Recent Pat Cardiovasc Drug Discov 6:222–241 Aliev G, Li Y, Palacios HH, Obrenovich ME (2011) Oxidative stress induced mitochondrial DNA deletion as a hallmark for the drug development in the context of the cerebrovascular diseases. Recent Pat Cardiovasc Drug Discov 6:222–241
Zurück zum Zitat Anderson KN, Shneerson JM (2009) Drug treatment of REM sleep behavior disorder: the use of drug therapies other than clonazepam. J Clin Sleep Med 5:235–239 Anderson KN, Shneerson JM (2009) Drug treatment of REM sleep behavior disorder: the use of drug therapies other than clonazepam. J Clin Sleep Med 5:235–239
Zurück zum Zitat Anderson KN, Jamieson S, Graham AJ, Shneerson JM (2008) REM sleep behaviour disorder treated with melatonin in a patient with Alzheimer’s disease. Clin Neurol Neurosurg 110:492–495 Anderson KN, Jamieson S, Graham AJ, Shneerson JM (2008) REM sleep behaviour disorder treated with melatonin in a patient with Alzheimer’s disease. Clin Neurol Neurosurg 110:492–495
Zurück zum Zitat Andrabi SA, Sayeed I, Siemen D, Wolf G, Horn TF (2004) Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J 18:869–871 Andrabi SA, Sayeed I, Siemen D, Wolf G, Horn TF (2004) Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J 18:869–871
Zurück zum Zitat Antolin I, Mayo JC, Sainz RM, del Brio ML, Herrera F, Martin V, Rodríguez C (2002) Protective effect of melatonin in a chronic experimental model of Parkinson’s disease. Brain Res 943:163–173 Antolin I, Mayo JC, Sainz RM, del Brio ML, Herrera F, Martin V, Rodríguez C (2002) Protective effect of melatonin in a chronic experimental model of Parkinson’s disease. Brain Res 943:163–173
Zurück zum Zitat Arendt J, Skene DJ, Middleton B, Lockley SW, Deacon S (1997) Efficacy of melatonin treatment in jet lag, shift work, and blindness. J Biol Rhythms 12:604–617 Arendt J, Skene DJ, Middleton B, Lockley SW, Deacon S (1997) Efficacy of melatonin treatment in jet lag, shift work, and blindness. J Biol Rhythms 12:604–617
Zurück zum Zitat Asayama K, Yamadera H, Ito T, Suzuki H, Kudo Y, Endo S (2003) Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia. J Nippon Med Sch 70:334–341 Asayama K, Yamadera H, Ito T, Suzuki H, Kudo Y, Endo S (2003) Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia. J Nippon Med Sch 70:334–341
Zurück zum Zitat Atanassova PA, Terzieva DD, Dimitrov BD (2009) Impaired nocturnal melatonin in acute phase of ischaemic stroke: cross-sectional matched case-control analysis. J Neuroendocrinol 21:657–663 Atanassova PA, Terzieva DD, Dimitrov BD (2009) Impaired nocturnal melatonin in acute phase of ischaemic stroke: cross-sectional matched case-control analysis. J Neuroendocrinol 21:657–663
Zurück zum Zitat Aurora RN, Zak RS, Maganti RK, Auerbach SH, Casey KR, Chowdhuri S, Karippot A, Ramar K, Kristo DA, Morgenthaler TI (2010) Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med 6:85–95 Aurora RN, Zak RS, Maganti RK, Auerbach SH, Casey KR, Chowdhuri S, Karippot A, Ramar K, Kristo DA, Morgenthaler TI (2010) Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med 6:85–95
Zurück zum Zitat Aziz NA, Pijl H, Frolich M, Schroder-van der Elst JP, van der BC, Roelfsema F, Roos RA (2009) Delayed onset of the diurnal melatonin rise in patients with Huntington’s disease. J Neurol 256:1961–1965 Aziz NA, Pijl H, Frolich M, Schroder-van der Elst JP, van der BC, Roelfsema F, Roos RA (2009) Delayed onset of the diurnal melatonin rise in patients with Huntington’s disease. J Neurol 256:1961–1965
Zurück zum Zitat Balzer I, Hardeland R (1991) Photoperiodism and effects of indoleamines in a unicellular alga, Gonyaulax polyedra. Science 253:795–797 Balzer I, Hardeland R (1991) Photoperiodism and effects of indoleamines in a unicellular alga, Gonyaulax polyedra. Science 253:795–797
Zurück zum Zitat Barzilai N, Gabriely I, Atzmon G, Suh Y, Rothenberg D, Bergman A (2010) Genetic studies reveal the role of the endocrine and metabolic systems in aging. J Clin Endocrinol Metab 95:4493–4500 Barzilai N, Gabriely I, Atzmon G, Suh Y, Rothenberg D, Bergman A (2010) Genetic studies reveal the role of the endocrine and metabolic systems in aging. J Clin Endocrinol Metab 95:4493–4500
Zurück zum Zitat Beatty S, Koh H, Phil M, Henson D, Boulton M (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45:115–134 Beatty S, Koh H, Phil M, Henson D, Boulton M (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45:115–134
Zurück zum Zitat Beck-Friis J, Kjellman BF, Aperia B, Unden F, von Rosen D, Ljunggren JG, Wetterberg L (1985) Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome. Acta Psychiatr Scand 71:319–330 Beck-Friis J, Kjellman BF, Aperia B, Unden F, von Rosen D, Ljunggren JG, Wetterberg L (1985) Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome. Acta Psychiatr Scand 71:319–330
Zurück zum Zitat Bedrosian TA, Herring KL, Weil ZM, Nelson RJ (2011) Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice. Proc Natl Acad Sci USA 108:11686–11691 Bedrosian TA, Herring KL, Weil ZM, Nelson RJ (2011) Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice. Proc Natl Acad Sci USA 108:11686–11691
Zurück zum Zitat Behrends A, Hardeland R, Ness H, Grube S, Poeggeler B, Haldar C (2004) Photocatalytic actions of the pesticide metabolite 2-hydroxyquinoxaline: destruction of antioxidant vitamins and biogenic amines—implications of organic redox cycling. Redox Rep 9:279–288 Behrends A, Hardeland R, Ness H, Grube S, Poeggeler B, Haldar C (2004) Photocatalytic actions of the pesticide metabolite 2-hydroxyquinoxaline: destruction of antioxidant vitamins and biogenic amines—implications of organic redox cycling. Redox Rep 9:279–288
Zurück zum Zitat Beni SM, Kohen R, Reiter RJ, Tan DX, Shohami E (2004) Melatonin-induced neuroprotection after closed head injury is associated with increased brain antioxidants and attenuated late-phase activation of NF-kappaB and AP-1. FASEB J 18:149–151 Beni SM, Kohen R, Reiter RJ, Tan DX, Shohami E (2004) Melatonin-induced neuroprotection after closed head injury is associated with increased brain antioxidants and attenuated late-phase activation of NF-kappaB and AP-1. FASEB J 18:149–151
Zurück zum Zitat Benítez-King G, Rios A, Martinez A, Anton-Tay F (1996) In vitro inhibition of Ca2+/calmodulin-dependent kinase II activity by melatonin. Biochim Biophys Acta 1290:191–196 Benítez-King G, Rios A, Martinez A, Anton-Tay F (1996) In vitro inhibition of Ca2+/calmodulin-dependent kinase II activity by melatonin. Biochim Biophys Acta 1290:191–196
Zurück zum Zitat Benítez-King G, Tunez I, Bellon A, Ortiz GG, Anton-Tay F (2003) Melatonin prevents cytoskeletal alterations and oxidative stress induced by okadaic acid in N1E-115 cells. Exp Neurol 182:151–159 Benítez-King G, Tunez I, Bellon A, Ortiz GG, Anton-Tay F (2003) Melatonin prevents cytoskeletal alterations and oxidative stress induced by okadaic acid in N1E-115 cells. Exp Neurol 182:151–159
Zurück zum Zitat Benítez-King G, Ramirez-Rodríguez G, Ortiz L, Meza I (2004) The neuronal cytoskeleton as a potential therapeutical target in neurodegenerative diseases and schizophrenia. Curr Drug Targets CNS Neurol Disord 3:515–533 Benítez-King G, Ramirez-Rodríguez G, Ortiz L, Meza I (2004) The neuronal cytoskeleton as a potential therapeutical target in neurodegenerative diseases and schizophrenia. Curr Drug Targets CNS Neurol Disord 3:515–533
Zurück zum Zitat Bergiannaki JD, Soldatos CR, Paparrigopoulos TJ, Syrengelas M, Stefanis CN (1995) Low and high melatonin excretors among healthy individuals. J Pineal Res 18:159–164 Bergiannaki JD, Soldatos CR, Paparrigopoulos TJ, Syrengelas M, Stefanis CN (1995) Low and high melatonin excretors among healthy individuals. J Pineal Res 18:159–164
Zurück zum Zitat Blackhall LJ (2012) Amyotrophic lateral sclerosis and palliative care: where we are, and the road ahead. Muscle Nerve 45:311–318 Blackhall LJ (2012) Amyotrophic lateral sclerosis and palliative care: where we are, and the road ahead. Muscle Nerve 45:311–318
Zurück zum Zitat Blask DE, Hill SM, Dauchy RT, Xiang S, Yuan L, Duplessis T, Mao L, Dauchy E, Sauer LA (2011) Circadian regulation of molecular, dietary, and metabolic signaling mechanisms of human breast cancer growth by the nocturnal melatonin signal and the consequences of its disruption by light at night. J Pineal Res 51:259–269 Blask DE, Hill SM, Dauchy RT, Xiang S, Yuan L, Duplessis T, Mao L, Dauchy E, Sauer LA (2011) Circadian regulation of molecular, dietary, and metabolic signaling mechanisms of human breast cancer growth by the nocturnal melatonin signal and the consequences of its disruption by light at night. J Pineal Res 51:259–269
Zurück zum Zitat Boeve BF, Silber MH, Ferman TJ (2003) Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med 4:281–284 Boeve BF, Silber MH, Ferman TJ (2003) Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med 4:281–284
Zurück zum Zitat Borah A, Mohanakumar KP (2009) Melatonin inhibits 6-hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents. J Pineal Res 47:293–300 Borah A, Mohanakumar KP (2009) Melatonin inhibits 6-hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents. J Pineal Res 47:293–300
Zurück zum Zitat Bordet R, Devos D, Brique S, Touitou Y, Guieu JD, Libersa C, Destee A (2003) Study of circadian melatonin secretion pattern at different stages of Parkinson’s disease. Clin Neuropharmacol 26:65–72 Bordet R, Devos D, Brique S, Touitou Y, Guieu JD, Libersa C, Destee A (2003) Study of circadian melatonin secretion pattern at different stages of Parkinson’s disease. Clin Neuropharmacol 26:65–72
Zurück zum Zitat Borlongan CV, Yamamoto M, Takei N, Kumazaki M, Ungsuparkorn C, Hida H, Sanberg PR, Nishino H (2000) Glial cell survival is enhanced during melatonin-induced neuroprotection against cerebral ischemia. FASEB J 14:1307–1317 Borlongan CV, Yamamoto M, Takei N, Kumazaki M, Ungsuparkorn C, Hida H, Sanberg PR, Nishino H (2000) Glial cell survival is enhanced during melatonin-induced neuroprotection against cerebral ischemia. FASEB J 14:1307–1317
Zurück zum Zitat Bouslama M, Renaud J, Olivier P, Fontaine RH, Matrot B, Gressens P, Gallego J (2007) Melatonin prevents learning disorders in brain-lesioned newborn mice. Neuroscience 150:712–719 Bouslama M, Renaud J, Olivier P, Fontaine RH, Matrot B, Gressens P, Gallego J (2007) Melatonin prevents learning disorders in brain-lesioned newborn mice. Neuroscience 150:712–719
Zurück zum Zitat Boveris DL, Boveris A (2007) Oxygen delivery to the tissues and mitochondrial respiration. Front Biosci 12:1014–1023 Boveris DL, Boveris A (2007) Oxygen delivery to the tissues and mitochondrial respiration. Front Biosci 12:1014–1023
Zurück zum Zitat Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134 Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134
Zurück zum Zitat Brown GM, Young SN, Gauthier S, Tsui H, Grota LJ (1979) Melatonin in human cerebrospinal fluid in daytime; its origin and variation with age. Life Sci 25:929–936 Brown GM, Young SN, Gauthier S, Tsui H, Grota LJ (1979) Melatonin in human cerebrospinal fluid in daytime; its origin and variation with age. Life Sci 25:929–936
Zurück zum Zitat Brown GM, Cardinali DP, Pandi-Perumal SR (2010) Melatonin and mental illness. In: Pandi-Perumal SR, Kramer M (eds) Sleep and Mental Illness. Cambridge University Press, Cambridge, pp 119–129 Brown GM, Cardinali DP, Pandi-Perumal SR (2010) Melatonin and mental illness. In: Pandi-Perumal SR, Kramer M (eds) Sleep and Mental Illness. Cambridge University Press, Cambridge, pp 119–129
Zurück zum Zitat Brusco LI, Marquez M, Cardinali DP (1998) Monozygotic twins with Alzheimer’s disease treated with melatonin: case report. J Pineal Res 25:260–263 Brusco LI, Marquez M, Cardinali DP (1998) Monozygotic twins with Alzheimer’s disease treated with melatonin: case report. J Pineal Res 25:260–263
Zurück zum Zitat Brusco LI, Marquez M, Cardinali DP (2000) Melatonin treatment stabilizes chronobiologic and cognitive symptoms in Alzheimer’s disease. Neuroendocrinol Lett 21:39–42 Brusco LI, Marquez M, Cardinali DP (2000) Melatonin treatment stabilizes chronobiologic and cognitive symptoms in Alzheimer’s disease. Neuroendocrinol Lett 21:39–42
Zurück zum Zitat Bubenik GA (2002) Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci 47:2336–2348 Bubenik GA (2002) Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci 47:2336–2348
Zurück zum Zitat Bubenik GA, Konturek SJ (2011) Melatonin and aging: prospects for human treatment. J Physiol Pharmacol 62:13–19 Bubenik GA, Konturek SJ (2011) Melatonin and aging: prospects for human treatment. J Physiol Pharmacol 62:13–19
Zurück zum Zitat Cai Y, Ding H, Li N, Chai Y, Zhang Y, Chan P (2010a) Oscillation development for neurotransmitter-related genes in the mouse striatum. NeuroReport 21:79–83 Cai Y, Ding H, Li N, Chai Y, Zhang Y, Chan P (2010a) Oscillation development for neurotransmitter-related genes in the mouse striatum. NeuroReport 21:79–83
Zurück zum Zitat Cai Y, Liu S, Sothern RB, Xu S, Chan P (2010b) Expression of clock genes Per1 and Bmal1 in total leukocytes in health and Parkinson’s disease. Eur J Neurol 17:550–554 Cai Y, Liu S, Sothern RB, Xu S, Chan P (2010b) Expression of clock genes Per1 and Bmal1 in total leukocytes in health and Parkinson’s disease. Eur J Neurol 17:550–554
Zurück zum Zitat Cardinali DP (1983) Molecular mechanisms of neuroendocrine integration in the central nervous system: an approach through the study of the pineal gland and its innervating sympathetic pathway. Psychoneuroendocrinology 8:3–30 Cardinali DP (1983) Molecular mechanisms of neuroendocrine integration in the central nervous system: an approach through the study of the pineal gland and its innervating sympathetic pathway. Psychoneuroendocrinology 8:3–30
Zurück zum Zitat Cardinali DP, Freire F (1975) Melatonin effects on brain. Interaction with microtubule protein, inhibition of fast axoplasmic flow and induction of crystaloid and tubular formations in the hypothalamus. Mol Cell Endocrinol 2:317–330 Cardinali DP, Freire F (1975) Melatonin effects on brain. Interaction with microtubule protein, inhibition of fast axoplasmic flow and induction of crystaloid and tubular formations in the hypothalamus. Mol Cell Endocrinol 2:317–330
Zurück zum Zitat Cardinali DP, Pévet P (1998) Basic aspects of melatonin action. Sleep Med Rev 2:175–190 Cardinali DP, Pévet P (1998) Basic aspects of melatonin action. Sleep Med Rev 2:175–190
Zurück zum Zitat Cardinali DP, Scacchi PA (2010) Chronophysiology of melatonin: therapeutical implications. Open Neuroendocrinol J 3:72–84 Cardinali DP, Scacchi PA (2010) Chronophysiology of melatonin: therapeutical implications. Open Neuroendocrinol J 3:72–84
Zurück zum Zitat Cardinali DP, Brusco LI, Liberczuk C, Furio AM (2002) The use of melatonin in Alzheimer’s disease. Neuroendocrinol Lett 23(suppl. 1):20–23 Cardinali DP, Brusco LI, Liberczuk C, Furio AM (2002) The use of melatonin in Alzheimer’s disease. Neuroendocrinol Lett 23(suppl. 1):20–23
Zurück zum Zitat Cardinali DP, Esquifino AI, Srinivasan V, Pandi-Perumal SR (2008) Melatonin and the immune system in aging. NeuroImmunoModulation 15:272–278 Cardinali DP, Esquifino AI, Srinivasan V, Pandi-Perumal SR (2008) Melatonin and the immune system in aging. NeuroImmunoModulation 15:272–278
Zurück zum Zitat Cardinali DP, Furio AM, Brusco LI (2010) Clinical aspects of melatonin intervention in Alzheimer’s disease progression. Curr Neuropharmacol 8:218–227 Cardinali DP, Furio AM, Brusco LI (2010) Clinical aspects of melatonin intervention in Alzheimer’s disease progression. Curr Neuropharmacol 8:218–227
Zurück zum Zitat Cardinali DP, Cano P, Jimenez-Ortega V, Esquifino AI (2011) Melatonin and the metabolic syndrome: physiopathologic and therapeutical implications. Neuroendocrinology 93:133–142 Cardinali DP, Cano P, Jimenez-Ortega V, Esquifino AI (2011) Melatonin and the metabolic syndrome: physiopathologic and therapeutical implications. Neuroendocrinology 93:133–142
Zurück zum Zitat Cardinali DP, Srinivasan V, Brzezinski A, Brown GM (2012) Melatonin and its analogs in insomnia and depression. J Pineal Res 52:365–375 Cardinali DP, Srinivasan V, Brzezinski A, Brown GM (2012) Melatonin and its analogs in insomnia and depression. J Pineal Res 52:365–375
Zurück zum Zitat Carneiro RC, Reiter RJ (1998) Melatonin protects against lipid peroxidation induced by delta-aminolevulinic acid in rat cerebellum, cortex and hippocampus. Neuroscience 82:293–299 Carneiro RC, Reiter RJ (1998) Melatonin protects against lipid peroxidation induced by delta-aminolevulinic acid in rat cerebellum, cortex and hippocampus. Neuroscience 82:293–299
Zurück zum Zitat Carrillo-Vico A, Reiter RJ, Lardone PJ, Herrera JL, Fernandez-Montesinos R, Guerrero JM, Pozo D (2006) The modulatory role of melatonin on immune responsiveness. Curr Opin Investig Drugs 7:423–431 Carrillo-Vico A, Reiter RJ, Lardone PJ, Herrera JL, Fernandez-Montesinos R, Guerrero JM, Pozo D (2006) The modulatory role of melatonin on immune responsiveness. Curr Opin Investig Drugs 7:423–431
Zurück zum Zitat Catala MD, Canete-Nicolas C, Iradi A, Tarazona PJ, Tormos JM, Pascual-Leóne A (1997) Melatonin levels in Parkinson’s disease: drug therapy versus electrical stimulation of the internal globus pallidus. Exp Gerontol 32:553–558 Catala MD, Canete-Nicolas C, Iradi A, Tarazona PJ, Tormos JM, Pascual-Leóne A (1997) Melatonin levels in Parkinson’s disease: drug therapy versus electrical stimulation of the internal globus pallidus. Exp Gerontol 32:553–558
Zurück zum Zitat Caumo W, Levandovski R, Hidalgo MP (2009) Preoperative anxiolytic effect of melatonin and clonidine on postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy: a double-blind, randomized, placebo-controlled study. J Pain 10:100–108 Caumo W, Levandovski R, Hidalgo MP (2009) Preoperative anxiolytic effect of melatonin and clonidine on postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy: a double-blind, randomized, placebo-controlled study. J Pain 10:100–108
Zurück zum Zitat Cavallo A (1993) Melatonin and human puberty: current perspectives. J Pineal Res 15:115–121 Cavallo A (1993) Melatonin and human puberty: current perspectives. J Pineal Res 15:115–121
Zurück zum Zitat Chahbouni M, Escames G, Venegas C, Sevilla B, García JA, Lopez LC, Munoz-Hoyos A, Molina-Carballo A, Acuña-Castroviejo D (2010) Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy. J Pineal Res 48:282–289 Chahbouni M, Escames G, Venegas C, Sevilla B, García JA, Lopez LC, Munoz-Hoyos A, Molina-Carballo A, Acuña-Castroviejo D (2010) Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy. J Pineal Res 48:282–289
Zurück zum Zitat Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605 Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605
Zurück zum Zitat Chen CM (2011) Mitochondrial dysfunction, metabolic deficits, and increased oxidative stress in Huntington’s disease. Chang Gung Med J 34:135–152 Chen CM (2011) Mitochondrial dysfunction, metabolic deficits, and increased oxidative stress in Huntington’s disease. Chang Gung Med J 34:135–152
Zurück zum Zitat Chen G, Huo Y, Tan DX, Liang Z, Zhang W, Zhang Y (2003) Melatonin in Chinese medicinal herbs. Life Sci 73:19–26 Chen G, Huo Y, Tan DX, Liang Z, Zhang W, Zhang Y (2003) Melatonin in Chinese medicinal herbs. Life Sci 73:19–26
Zurück zum Zitat Cheung RT (2003) The utility of melatonin in reducing cerebral damage resulting from ischemia and reperfusion. J Pineal Res 34:153–160 Cheung RT (2003) The utility of melatonin in reducing cerebral damage resulting from ischemia and reperfusion. J Pineal Res 34:153–160
Zurück zum Zitat Cho S, Joh TH, Baik HH, Dibinis C, Volpe BT (1997) Melatonin administration protects CA1 hippocampal neurons after transient forebrain ischemia in rats. Brain Res 755:335–338 Cho S, Joh TH, Baik HH, Dibinis C, Volpe BT (1997) Melatonin administration protects CA1 hippocampal neurons after transient forebrain ischemia in rats. Brain Res 755:335–338
Zurück zum Zitat Chuang YC (2010) Mitochondrial dysfunction and oxidative stress in seizure-induced neuronal cell death. Acta Neurol Taiwan 19:3–15 Chuang YC (2010) Mitochondrial dysfunction and oxidative stress in seizure-induced neuronal cell death. Acta Neurol Taiwan 19:3–15
Zurück zum Zitat Chuang JI, Chen TH (2004) Effect of melatonin on temporal changes of reactive oxygen species and glutathione after MPP+ treatment in human astrocytoma U373MG cells. J Pineal Res 36:117–125 Chuang JI, Chen TH (2004) Effect of melatonin on temporal changes of reactive oxygen species and glutathione after MPP+ treatment in human astrocytoma U373MG cells. J Pineal Res 36:117–125
Zurück zum Zitat Claustrat B, Brun J, Chazot G (2005) The basic physiology and pathophysiology of melatonin. Sleep Med Rev 9:11–24 Claustrat B, Brun J, Chazot G (2005) The basic physiology and pathophysiology of melatonin. Sleep Med Rev 9:11–24
Zurück zum Zitat Cohen-Mansfield J, Garfinkel D, Lipson S (2000) Melatonin for treatment of sundowning in elderly persons with dementia—a preliminary study. Arch Gerontol Geriatr 31:65–76 Cohen-Mansfield J, Garfinkel D, Lipson S (2000) Melatonin for treatment of sundowning in elderly persons with dementia—a preliminary study. Arch Gerontol Geriatr 31:65–76
Zurück zum Zitat Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni JM (2000) Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res 28:193–202 Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni JM (2000) Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res 28:193–202
Zurück zum Zitat Cunningham C (2011) Systemic inflammation and delirium: important co-factors in the progression of dementia. Biochem Soc Trans 39:945–953 Cunningham C (2011) Systemic inflammation and delirium: important co-factors in the progression of dementia. Biochem Soc Trans 39:945–953
Zurück zum Zitat Cuzzocrea S, Zingarelli B, Gilad E, Hake P, Salzman AL, Szabo C (1997) Protective effect of melatonin in carrageenan-induced models of local inflammation: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J Pineal Res 23:106–116 Cuzzocrea S, Zingarelli B, Gilad E, Hake P, Salzman AL, Szabo C (1997) Protective effect of melatonin in carrageenan-induced models of local inflammation: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J Pineal Res 23:106–116
Zurück zum Zitat Dabbeni-Sala F, Di Santo S, Franceschini D, Skaper SD, Giusti P (2001) Melatonin protects against 6-OHDA-induced neurotoxicity in rats: a role for mitochondrial complex I activity. FASEB J 15:164–170 Dabbeni-Sala F, Di Santo S, Franceschini D, Skaper SD, Giusti P (2001) Melatonin protects against 6-OHDA-induced neurotoxicity in rats: a role for mitochondrial complex I activity. FASEB J 15:164–170
Zurück zum Zitat Dardente H (2012) Melatonin-dependent timing of seasonal reproduction by the pars tuberalis: pivotal roles for long daylengths and thyroid hormones. J Neuroendocrinol 24:249–266 Dardente H (2012) Melatonin-dependent timing of seasonal reproduction by the pars tuberalis: pivotal roles for long daylengths and thyroid hormones. J Neuroendocrinol 24:249–266
Zurück zum Zitat Das A, McDowell M, Pava MJ, Smith JA, Reiter RJ, Woodward JJ, Varma AK, Ray SK, Banik NL (2010) The inhibition of apoptosis by melatonin in VSC4.1 motoneurons exposed to oxidative stress, glutamate excitotoxicity, or TNF-alpha toxicity involves membrane melatonin receptors. J Pineal Res 48:157–169 Das A, McDowell M, Pava MJ, Smith JA, Reiter RJ, Woodward JJ, Varma AK, Ray SK, Banik NL (2010) The inhibition of apoptosis by melatonin in VSC4.1 motoneurons exposed to oxidative stress, glutamate excitotoxicity, or TNF-alpha toxicity involves membrane melatonin receptors. J Pineal Res 48:157–169
Zurück zum Zitat Dawson D, Armstrong SM (1996) Chronobiotics—drugs that shift rhythms. Pharmacol Ther 69:15–36 Dawson D, Armstrong SM (1996) Chronobiotics—drugs that shift rhythms. Pharmacol Ther 69:15–36
Zurück zum Zitat de Jonghe A, Korevaar JC, van Munster BC, de Rooij SE (2010) Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review. Int J Geriatr Psychiatry 25:1201–1208 de Jonghe A, Korevaar JC, van Munster BC, de Rooij SE (2010) Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review. Int J Geriatr Psychiatry 25:1201–1208
Zurück zum Zitat Devore EE, Grodstein F, van Rooij FJ, Hofman A, Stampfer MJ, Witteman JC, Breteler MM (2010) Dietary antioxidants and long-term risk of dementia. Arch Neurol 67:819–825 Devore EE, Grodstein F, van Rooij FJ, Hofman A, Stampfer MJ, Witteman JC, Breteler MM (2010) Dietary antioxidants and long-term risk of dementia. Arch Neurol 67:819–825
Zurück zum Zitat Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, Jenner P, Marsden CD (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52:381–389 Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, Jenner P, Marsden CD (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52:381–389
Zurück zum Zitat Domínguez-Rodríguez A, Abreu-Gonzalez P, Sanchez–Sanchez JJ, Kaski JC, Reiter RJ (2010) Melatonin and circadian biology in human cardiovascular disease. J Pineal Res 49:14–22 Domínguez-Rodríguez A, Abreu-Gonzalez P, Sanchez–Sanchez JJ, Kaski JC, Reiter RJ (2010) Melatonin and circadian biology in human cardiovascular disease. J Pineal Res 49:14–22
Zurück zum Zitat Dori D, Casale G, Solerte SB, Fioravanti M, Migliorati G, Cuzzoni G, Ferrari E (1994) Chrono-neuroendocrinological aspects of physiological aging and senile dementia. Chronobiologia 21:121–126 Dori D, Casale G, Solerte SB, Fioravanti M, Migliorati G, Cuzzoni G, Ferrari E (1994) Chrono-neuroendocrinological aspects of physiological aging and senile dementia. Chronobiologia 21:121–126
Zurück zum Zitat Dowling GA, Mastick J, Colling E, Carter JH, Singer CM, Aminoff MJ (2005) Melatonin for sleep disturbances in Parkinson’s disease. Sleep Med 6:459–466 Dowling GA, Mastick J, Colling E, Carter JH, Singer CM, Aminoff MJ (2005) Melatonin for sleep disturbances in Parkinson’s disease. Sleep Med 6:459–466
Zurück zum Zitat Dowling GA, Burr RL, Van Someren EJ, Hubbard EM, Luxenberg JS, Mastick J, Cooper BA (2008) Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer’s disease. J Am Geriatr Soc 56:239–246 Dowling GA, Burr RL, Van Someren EJ, Hubbard EM, Luxenberg JS, Mastick J, Cooper BA (2008) Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer’s disease. J Am Geriatr Soc 56:239–246
Zurück zum Zitat Dragicevic N, Copes N, O’Neal-Moffitt G, Jin J, Buzzeo R, Mamcarz M, Tan J, Cao C, Olcese JM, Arendash GW, Bradshaw PC (2011) Melatonin treatment restores mitochondrial function in Alzheimer’s mice: a mitochondrial protective role of melatonin membrane receptor signaling. J Pineal Res 51:75–86 Dragicevic N, Copes N, O’Neal-Moffitt G, Jin J, Buzzeo R, Mamcarz M, Tan J, Cao C, Olcese JM, Arendash GW, Bradshaw PC (2011) Melatonin treatment restores mitochondrial function in Alzheimer’s mice: a mitochondrial protective role of melatonin membrane receptor signaling. J Pineal Res 51:75–86
Zurück zum Zitat Dubbels R, Reiter RJ, Klenke E, Goebel A, Schnakenberg E, Ehlers C, Schiwara HW, Schloot W (1995) Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry. J Pineal Res 18:28–31 Dubbels R, Reiter RJ, Klenke E, Goebel A, Schnakenberg E, Ehlers C, Schiwara HW, Schloot W (1995) Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry. J Pineal Res 18:28–31
Zurück zum Zitat Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J (2010) International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev 62:343–380 Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J (2010) International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev 62:343–380
Zurück zum Zitat Ehrnhoefer DE, Wong BK, Hayden MR (2011) Convergent pathogenic pathways in Alzheimer’s and Huntington’s diseases: shared targets for drug development. Nat Rev Drug Discov 10:853–867 Ehrnhoefer DE, Wong BK, Hayden MR (2011) Convergent pathogenic pathways in Alzheimer’s and Huntington’s diseases: shared targets for drug development. Nat Rev Drug Discov 10:853–867
Zurück zum Zitat Erol FS, Topsakal C, Ozveren MF, Kaplan M, Ilhan N, Ozercan IH, Yildiz OG (2004) Protective effects of melatonin and vitamin E in brain damage due to gamma radiation: an experimental study. Neurosurg Rev 27:65–69 Erol FS, Topsakal C, Ozveren MF, Kaplan M, Ilhan N, Ozercan IH, Yildiz OG (2004) Protective effects of melatonin and vitamin E in brain damage due to gamma radiation: an experimental study. Neurosurg Rev 27:65–69
Zurück zum Zitat Escames G, Acuña-Castroviejo CD, Vives F (1996) Melatonin–dopamine interaction in the striatal projection area of sensorimotor cortex in the rat. NeuroReport 7:597–600 Escames G, Acuña-Castroviejo CD, Vives F (1996) Melatonin–dopamine interaction in the striatal projection area of sensorimotor cortex in the rat. NeuroReport 7:597–600
Zurück zum Zitat Escames G, León J, Lopez LC, Acuña-Castroviejo D (2004) Mechanisms of N-methyl-d-aspartate receptor inhibition by melatonin in the rat striatum. J Neuroendocrinol 16:929–935 Escames G, León J, Lopez LC, Acuña-Castroviejo D (2004) Mechanisms of N-methyl-d-aspartate receptor inhibition by melatonin in the rat striatum. J Neuroendocrinol 16:929–935
Zurück zum Zitat Esposito E, Cuzzocrea S (2010) Antiinflammatory activity of melatonin in central nervous system. Curr Neuropharmacol 8:228–242 Esposito E, Cuzzocrea S (2010) Antiinflammatory activity of melatonin in central nervous system. Curr Neuropharmacol 8:228–242
Zurück zum Zitat Esquifino AI, Pandi-Perumal SR, Cardinali DP (2004) Circadian organization of the immune response: a role for melatonin. Clin Applied Immunol Rev 4:423–433 Esquifino AI, Pandi-Perumal SR, Cardinali DP (2004) Circadian organization of the immune response: a role for melatonin. Clin Applied Immunol Rev 4:423–433
Zurück zum Zitat Fahn S, Cohen G (1992) The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 32:804–812 Fahn S, Cohen G (1992) The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 32:804–812
Zurück zum Zitat Fainstein I, Bonetto A, Brusco LI, Cardinali DP (1997) Effects of melatonin in elderly patients with sleep disturbance. A pilot study. Curr Ther Res 58:990–1000 Fainstein I, Bonetto A, Brusco LI, Cardinali DP (1997) Effects of melatonin in elderly patients with sleep disturbance. A pilot study. Curr Ther Res 58:990–1000
Zurück zum Zitat Feng Z, Zhang JT (2004) Melatonin reduces amyloid beta-induced apoptosis in pheochromocytoma (PC12) cells. J Pineal Res 37:257–266 Feng Z, Zhang JT (2004) Melatonin reduces amyloid beta-induced apoptosis in pheochromocytoma (PC12) cells. J Pineal Res 37:257–266
Zurück zum Zitat Feng Z, Qin C, Chang Y, Zhang JT (2006) Early melatonin supplementation alleviates oxidative stress in a transgenic mouse model of Alzheimer’s disease. Free Radic Biol Med 40:101–109 Feng Z, Qin C, Chang Y, Zhang JT (2006) Early melatonin supplementation alleviates oxidative stress in a transgenic mouse model of Alzheimer’s disease. Free Radic Biol Med 40:101–109
Zurück zum Zitat Ferrari E, Fioravanti M, Magri F, Solerte SB (2000) Variability of interactions between neuroendocrine and immunological functions in physiological aging and dementia of the Alzheimer’s type. Ann N Y Acad Sci 917:582–596 Ferrari E, Fioravanti M, Magri F, Solerte SB (2000) Variability of interactions between neuroendocrine and immunological functions in physiological aging and dementia of the Alzheimer’s type. Ann N Y Acad Sci 917:582–596
Zurück zum Zitat Ferrari E, Cravello L, Falvo F, Barili L, Solerte SB, Fioravanti M, Magri F (2008) Neuroendocrine features in extreme longevity. Exp Gerontol 43:88–94 Ferrari E, Cravello L, Falvo F, Barili L, Solerte SB, Fioravanti M, Magri F (2008) Neuroendocrine features in extreme longevity. Exp Gerontol 43:88–94
Zurück zum Zitat Fertl E, Auff E, Doppelbauer A, Waldhauser F (1993) Circadian secretion pattern of melatonin in de novo parkinsonian patients: evidence for phase-shifting properties of l-dopa. J Neural Transm Park Dis Dement Sect 5:227–234 Fertl E, Auff E, Doppelbauer A, Waldhauser F (1993) Circadian secretion pattern of melatonin in de novo parkinsonian patients: evidence for phase-shifting properties of l-dopa. J Neural Transm Park Dis Dement Sect 5:227–234
Zurück zum Zitat Floden AM, Li S, Combs CK (2005) Beta-amyloid-stimulated microglia induce neuron death via synergistic stimulation of tumor necrosis factor alpha and NMDA receptors. J Neurosci 25:2566–2575 Floden AM, Li S, Combs CK (2005) Beta-amyloid-stimulated microglia induce neuron death via synergistic stimulation of tumor necrosis factor alpha and NMDA receptors. J Neurosci 25:2566–2575
Zurück zum Zitat Fourtillan JB, Brisson AM, Fourtillan M, Ingrand I, Decourt JP, Girault J (2001) Melatonin secretion occurs at a constant rate in both young and older men and women. Am J Physiol Endocrinol Metab 280:E11–E22 Fourtillan JB, Brisson AM, Fourtillan M, Ingrand I, Decourt JP, Girault J (2001) Melatonin secretion occurs at a constant rate in both young and older men and women. Am J Physiol Endocrinol Metab 280:E11–E22
Zurück zum Zitat Fraser PA (2011) The role of free radical generation in increasing cerebrovascular permeability. Free Radic Biol Med 51:967–977 Fraser PA (2011) The role of free radical generation in increasing cerebrovascular permeability. Free Radic Biol Med 51:967–977
Zurück zum Zitat Furio AM, Cutrera RA, Castillo TV, Perez LS, Riccio P, Caccuri RL, Brusco LL, Cardinali DP (2002) Effect of melatonin on changes in locomotor activity rhythm of Syrian hamsters injected with beta amyloid peptide 25–35 in the suprachiasmatic nuclei. Cell Mol Neurobiol 22:699–709 Furio AM, Cutrera RA, Castillo TV, Perez LS, Riccio P, Caccuri RL, Brusco LL, Cardinali DP (2002) Effect of melatonin on changes in locomotor activity rhythm of Syrian hamsters injected with beta amyloid peptide 25–35 in the suprachiasmatic nuclei. Cell Mol Neurobiol 22:699–709
Zurück zum Zitat Furio AM, Brusco LI, Cardinali DP (2007) Possible therapeutic value of melatonin in mild cognitive impairment: a retrospective study. J Pineal Res 43:404–409 Furio AM, Brusco LI, Cardinali DP (2007) Possible therapeutic value of melatonin in mild cognitive impairment: a retrospective study. J Pineal Res 43:404–409
Zurück zum Zitat Furio AM, Fontao R, Falco N, Ruiz JI, Caccuri RL, Cardinali DP (2008) Neuroprotective effect of melatonin on glucocorticoid toxicity in the rat hippocampus. Open Physiol J 1:23–27 Furio AM, Fontao R, Falco N, Ruiz JI, Caccuri RL, Cardinali DP (2008) Neuroprotective effect of melatonin on glucocorticoid toxicity in the rat hippocampus. Open Physiol J 1:23–27
Zurück zum Zitat Galano A, Tan DX, Reiter RJ (2011) Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res 51:1–16 Galano A, Tan DX, Reiter RJ (2011) Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res 51:1–16
Zurück zum Zitat Galecki P, Szemraj J, Bartosz G, Bienkiewicz M, Galecka E, Florkowski A, Lewinski A, Karbownik-Lewinska M (2010) Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder. J Pineal Res 48:311–317 Galecki P, Szemraj J, Bartosz G, Bienkiewicz M, Galecka E, Florkowski A, Lewinski A, Karbownik-Lewinska M (2010) Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder. J Pineal Res 48:311–317
Zurück zum Zitat García JJ, Reiter RJ, Pie J, Ortiz GG, Cabrera J, Sainz RM, Acuña-Castroviejo D (1999) Role of pinoline and melatonin in stabilizing hepatic microsomal membranes against oxidative stress. J Bioenerg Biomembr 31:609–616 García JJ, Reiter RJ, Pie J, Ortiz GG, Cabrera J, Sainz RM, Acuña-Castroviejo D (1999) Role of pinoline and melatonin in stabilizing hepatic microsomal membranes against oxidative stress. J Bioenerg Biomembr 31:609–616
Zurück zum Zitat García T, Ribes D, Colomina MT, Cabre M, Domingo JL, Gomez M (2009) Evaluation of the protective role of melatonin on the behavioral effects of aluminum in a mouse model of Alzheimer’s disease. Toxicology 265:49–55 García T, Ribes D, Colomina MT, Cabre M, Domingo JL, Gomez M (2009) Evaluation of the protective role of melatonin on the behavioral effects of aluminum in a mouse model of Alzheimer’s disease. Toxicology 265:49–55
Zurück zum Zitat García T, Esparza JL, Nogues MR, Romeu M, Domingo JL, Gomez M (2010) Oxidative stress status and RNA expression in hippocampus of an animal model of Alzheimer’s disease after chronic exposure to aluminum. Hippocampus 20:218–225 García T, Esparza JL, Nogues MR, Romeu M, Domingo JL, Gomez M (2010) Oxidative stress status and RNA expression in hippocampus of an animal model of Alzheimer’s disease after chronic exposure to aluminum. Hippocampus 20:218–225
Zurück zum Zitat García-Mesa Y, Gimenez-Llort L, Lopez LC, Venegas C, Cristofol R, Escames G, Acuña-Castroviejo D, Sanfeliu C (2012) Melatonin plus physical exercise are highly neuroprotective in the 3xTg-AD mouse. Neurobiol Aging 33:1124–1129 García-Mesa Y, Gimenez-Llort L, Lopez LC, Venegas C, Cristofol R, Escames G, Acuña-Castroviejo D, Sanfeliu C (2012) Melatonin plus physical exercise are highly neuroprotective in the 3xTg-AD mouse. Neurobiol Aging 33:1124–1129
Zurück zum Zitat Garzon C, Guerrero JM, Aramburu O, Guzman T (2009) Effect of melatonin administration on sleep, behavioral disorders and hypnotic drug discontinuation in the elderly: a randomized, double-blind, placebo-controlled study. Aging Clin Exp Res 21:38–42 Garzon C, Guerrero JM, Aramburu O, Guzman T (2009) Effect of melatonin administration on sleep, behavioral disorders and hypnotic drug discontinuation in the elderly: a randomized, double-blind, placebo-controlled study. Aging Clin Exp Res 21:38–42
Zurück zum Zitat Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow H, Cummings JL, de León M, Feldman H, Ganguli M, Hampel H, Scheltens P, Tierney MC, Whitehouse P, Winblad B (2006) Mild cognitive impairment. Lancet 367:1262–1270 Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow H, Cummings JL, de León M, Feldman H, Ganguli M, Hampel H, Scheltens P, Tierney MC, Whitehouse P, Winblad B (2006) Mild cognitive impairment. Lancet 367:1262–1270
Zurück zum Zitat Gehrman PR, Connor DJ, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S (2009) Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. Am J Geriatr Psychiatry 17:166–169 Gehrman PR, Connor DJ, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S (2009) Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. Am J Geriatr Psychiatry 17:166–169
Zurück zum Zitat Genova ML, Pich MM, Bernacchia A, Bianchi C, Biondi A, Bovina C, Falasca AI, Formiggini G, Castelli GP, Lenaz G (2004) The mitochondrial production of reactive oxygen species in relation to aging and pathology. Ann N Y Acad Sci 1011:86–100 Genova ML, Pich MM, Bernacchia A, Bianchi C, Biondi A, Bovina C, Falasca AI, Formiggini G, Castelli GP, Lenaz G (2004) The mitochondrial production of reactive oxygen species in relation to aging and pathology. Ann N Y Acad Sci 1011:86–100
Zurück zum Zitat Ghanta S, Chattopadhyay S (2011) Glutathione as a signaling molecule: another challenge to pathogens. Plant Signal Behav 6:783–788 Ghanta S, Chattopadhyay S (2011) Glutathione as a signaling molecule: another challenge to pathogens. Plant Signal Behav 6:783–788
Zurück zum Zitat Gibson GE, Starkov A, Blass JP, Ratan RR, Beal MF (2010) Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases. Biochim Biophys Acta 1802:122–134 Gibson GE, Starkov A, Blass JP, Ratan RR, Beal MF (2010) Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases. Biochim Biophys Acta 1802:122–134
Zurück zum Zitat Girotti L, Lago M, Ianovsky O, Carbajales J, Elizari MV, Brusco LI, Cardinali DP (2000) Low urinary 6-sulphatoxymelatonin levels in patients with coronary artery disease. J Pineal Res 29:138–142 Girotti L, Lago M, Ianovsky O, Carbajales J, Elizari MV, Brusco LI, Cardinali DP (2000) Low urinary 6-sulphatoxymelatonin levels in patients with coronary artery disease. J Pineal Res 29:138–142
Zurück zum Zitat Giusti P, Franceschini D, Petrone M, Manev H, Floreani M (1996a) In vitro and in vivo protection against kainate-induced excitotoxicity by melatonin. J Pineal Res 20:226–231 Giusti P, Franceschini D, Petrone M, Manev H, Floreani M (1996a) In vitro and in vivo protection against kainate-induced excitotoxicity by melatonin. J Pineal Res 20:226–231
Zurück zum Zitat Giusti P, Lipartiti M, Franceschini D, Schiavo N, Floreani M, Manev H (1996b) Neuroprotection by melatonin from kainate-induced excitotoxicity in rats. FASEB J 10:891–896 Giusti P, Lipartiti M, Franceschini D, Schiavo N, Floreani M, Manev H (1996b) Neuroprotection by melatonin from kainate-induced excitotoxicity in rats. FASEB J 10:891–896
Zurück zum Zitat Golombek DA, Pévet P, Cardinali DP (1996) Melatonin effects on behavior: possible mediation by the central GABAergic system. Neurosci Biobehav Rev 20:403–412 Golombek DA, Pévet P, Cardinali DP (1996) Melatonin effects on behavior: possible mediation by the central GABAergic system. Neurosci Biobehav Rev 20:403–412
Zurück zum Zitat Gorgulu A, Palaoglu S, Ismailoglu O, Tuncel M, Surucu MT, Erbil M, Kilinc K (2001) Effect of melatonin on cerebral edema in rats. Neurosurgery 49:1434–1441 Gorgulu A, Palaoglu S, Ismailoglu O, Tuncel M, Surucu MT, Erbil M, Kilinc K (2001) Effect of melatonin on cerebral edema in rats. Neurosurgery 49:1434–1441
Zurück zum Zitat Green DR, Galluzzi L, Kroemer G (2011) Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science 333:1109–1112 Green DR, Galluzzi L, Kroemer G (2011) Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science 333:1109–1112
Zurück zum Zitat Grinberg LT, Rueb U, Alho AT, Heinsen H (2010) Brainstem pathology and non-motor symptoms in PD. J Neurol Sci 289:81–88 Grinberg LT, Rueb U, Alho AT, Heinsen H (2010) Brainstem pathology and non-motor symptoms in PD. J Neurol Sci 289:81–88
Zurück zum Zitat Grof E, Grof P, Brown GM, Arato M, Lane J (1985) Investigations of melatonin secretion in man. Prog Neuropsychopharmacol Biol Psychiatry 9:609–612 Grof E, Grof P, Brown GM, Arato M, Lane J (1985) Investigations of melatonin secretion in man. Prog Neuropsychopharmacol Biol Psychiatry 9:609–612
Zurück zum Zitat Guerrero JM, Reiter RJ (2002) Melatonin-immune system relationships. Curr Top Med Chem 2:167–179 Guerrero JM, Reiter RJ (2002) Melatonin-immune system relationships. Curr Top Med Chem 2:167–179
Zurück zum Zitat Guerrero JM, Reiter RJ, Ortiz GG, Pablos MI, Sewerynek E, Chuang JI (1997) Melatonin prevents increases in neural nitric oxide and cyclic GMP production after transient brain ischemia and reperfusion in the Mongolian gerbil (Meriones unguiculatus). J Pineal Res 23:24–31 Guerrero JM, Reiter RJ, Ortiz GG, Pablos MI, Sewerynek E, Chuang JI (1997) Melatonin prevents increases in neural nitric oxide and cyclic GMP production after transient brain ischemia and reperfusion in the Mongolian gerbil (Meriones unguiculatus). J Pineal Res 23:24–31
Zurück zum Zitat Guido ME, Garbarino-Pico E, Contin MA, Valdez DJ, Nieto PS, Verra DM, Acosta-Rodríguez VA, de Zavalia N, Rosenstein RE (2010) Inner retinal circadian clocks and non-visual photoreceptors: novel players in the circadian system. Prog Neurobiol 92:484–504 Guido ME, Garbarino-Pico E, Contin MA, Valdez DJ, Nieto PS, Verra DM, Acosta-Rodríguez VA, de Zavalia N, Rosenstein RE (2010) Inner retinal circadian clocks and non-visual photoreceptors: novel players in the circadian system. Prog Neurobiol 92:484–504
Zurück zum Zitat Gupta M, Gupta YK, Agarwal S, Aneja S, Kalaivani M, Kohli K (2004) Effects of add-on melatonin administration on antioxidant enzymes in children with epilepsy taking carbamazepine monotherapy: a randomized, double-blind, placebo-controlled trial. Epilepsia 45:1636–1639 Gupta M, Gupta YK, Agarwal S, Aneja S, Kalaivani M, Kohli K (2004) Effects of add-on melatonin administration on antioxidant enzymes in children with epilepsy taking carbamazepine monotherapy: a randomized, double-blind, placebo-controlled trial. Epilepsia 45:1636–1639
Zurück zum Zitat Hall ED (2011) Antioxidant therapies for acute spinal cord injury. Neurotherapeutics 8:152–167 Hall ED (2011) Antioxidant therapies for acute spinal cord injury. Neurotherapeutics 8:152–167
Zurück zum Zitat Hall NF, Gale CR (2002) Prevention of age related macular degeneration. BMJ 325:1–2 Hall NF, Gale CR (2002) Prevention of age related macular degeneration. BMJ 325:1–2
Zurück zum Zitat Hall ED, Vaishnav RA, Mustafa AG (2010) Antioxidant therapies for traumatic brain injury. Neurotherapeutics 7:51–61 Hall ED, Vaishnav RA, Mustafa AG (2010) Antioxidant therapies for traumatic brain injury. Neurotherapeutics 7:51–61
Zurück zum Zitat Harada S, Fujii C, Hayashi A, Ohkoshi N (2001) An association between idiopathic Parkinson’s disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2. Biochem Biophys Res Commun 288:887–892 Harada S, Fujii C, Hayashi A, Ohkoshi N (2001) An association between idiopathic Parkinson’s disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2. Biochem Biophys Res Commun 288:887–892
Zurück zum Zitat Hardeland R (2005) Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 27:119–130 Hardeland R (2005) Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 27:119–130
Zurück zum Zitat Hardeland R (2008) Melatonin, hormone of darkness and more—occurrence, control mechanisms, actions and bioactive metabolites. Cell Mol Life Sci 65:2001–2018 Hardeland R (2008) Melatonin, hormone of darkness and more—occurrence, control mechanisms, actions and bioactive metabolites. Cell Mol Life Sci 65:2001–2018
Zurück zum Zitat Hardeland R (2009a) Melatonin: signaling mechanisms of a pleiotropic agent. BioFactors 35:183–192 Hardeland R (2009a) Melatonin: signaling mechanisms of a pleiotropic agent. BioFactors 35:183–192
Zurück zum Zitat Hardeland R (2009b) Neuroprotection by radical avoidance: search for suitable agents. Molecules 14:5054–5102 Hardeland R (2009b) Neuroprotection by radical avoidance: search for suitable agents. Molecules 14:5054–5102
Zurück zum Zitat Hardeland R (2010a) Investigational melatonin receptor agonists. Expert Opin Investig Drugs 19:747–764 Hardeland R (2010a) Investigational melatonin receptor agonists. Expert Opin Investig Drugs 19:747–764
Zurück zum Zitat Hardeland R (2010b) Melatonin metabolism in the central nervous system. Curr Neuropharmacol 8:168–181 Hardeland R (2010b) Melatonin metabolism in the central nervous system. Curr Neuropharmacol 8:168–181
Zurück zum Zitat Hardeland R, Pandi-Perumal SR (2005) Melatonin, a potent agent in antioxidative defense: actions as a natural food constituent, gastrointestinal factor, drug and prodrug. Nutr Metab (Lond) 2:22 Hardeland R, Pandi-Perumal SR (2005) Melatonin, a potent agent in antioxidative defense: actions as a natural food constituent, gastrointestinal factor, drug and prodrug. Nutr Metab (Lond) 2:22
Zurück zum Zitat Hardeland R, Poeggeler B (2007) Actions of melatonin, its structural and functional analogs in the central nervous system and the significance of metabolism. Cent Nerv Syst Agents Med Chem 7:303 Hardeland R, Poeggeler B (2007) Actions of melatonin, its structural and functional analogs in the central nervous system and the significance of metabolism. Cent Nerv Syst Agents Med Chem 7:303
Zurück zum Zitat Hardeland R, Poeggeler B (2008) Melatonin beyond its classical functions. Open Physiol J 1:1–23 Hardeland R, Poeggeler B (2008) Melatonin beyond its classical functions. Open Physiol J 1:1–23
Zurück zum Zitat Hardeland R, Balzer I, Poeggeler B, Fuhrberg B, Uria H, Behrmann G, Wolf R, Meyer TJ, Reiter RJ (1995) On the primary functions of melatonin in evolution: mediation of photoperiodic signals in a unicell, photooxidation, and scavenging of free radicals. J Pineal Res 18:104–111 Hardeland R, Balzer I, Poeggeler B, Fuhrberg B, Uria H, Behrmann G, Wolf R, Meyer TJ, Reiter RJ (1995) On the primary functions of melatonin in evolution: mediation of photoperiodic signals in a unicell, photooxidation, and scavenging of free radicals. J Pineal Res 18:104–111
Zurück zum Zitat Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR (2011) Melatonin-A pleiotropic, orchestrating regulator molecule. Prog Neurobiol 93:350–384 Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR (2011) Melatonin-A pleiotropic, orchestrating regulator molecule. Prog Neurobiol 93:350–384
Zurück zum Zitat Hausman DB, Fischer JG, Johnson MA (2011) Nutrition in centenarians. Maturitas 68:203–209 Hausman DB, Fischer JG, Johnson MA (2011) Nutrition in centenarians. Maturitas 68:203–209
Zurück zum Zitat He H, Dong W, Huang F (2010) Anti-amyloidogenic and anti-apoptotic role of melatonin in Alzheimer disease. Curr Neuropharmacol 8:211–217 He H, Dong W, Huang F (2010) Anti-amyloidogenic and anti-apoptotic role of melatonin in Alzheimer disease. Curr Neuropharmacol 8:211–217
Zurück zum Zitat Heiser V, Scherzinger E, Boeddrich A, Nordhoff E, Lurz R, Schugardt N, Lehrach H, Wanker EE (2000) Inhibition of huntingtin fibrillogenesis by specific antibodies and small molecules: implications for Huntington’s disease therapy. Proc Natl Acad Sci USA 97:6739–6744 Heiser V, Scherzinger E, Boeddrich A, Nordhoff E, Lurz R, Schugardt N, Lehrach H, Wanker EE (2000) Inhibition of huntingtin fibrillogenesis by specific antibodies and small molecules: implications for Huntington’s disease therapy. Proc Natl Acad Sci USA 97:6739–6744
Zurück zum Zitat Hu K, Van Someren EJ, Shea SA, Scheer FA (2009) Reduction of scale invariance of activity fluctuations with aging and Alzheimer’s disease: involvement of the circadian pacemaker. Proc Natl Acad Sci USA 106:2490–2494 Hu K, Van Someren EJ, Shea SA, Scheer FA (2009) Reduction of scale invariance of activity fluctuations with aging and Alzheimer’s disease: involvement of the circadian pacemaker. Proc Natl Acad Sci USA 106:2490–2494
Zurück zum Zitat Huether G (1993) The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates. Experientia 49:665–670 Huether G (1993) The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates. Experientia 49:665–670
Zurück zum Zitat Huether G (1994) Melatonin synthesis in the gastrointestinal tract and the impact of nutritional factors on circulating melatonin. Ann N Y Acad Sci 719:146–158 Huether G (1994) Melatonin synthesis in the gastrointestinal tract and the impact of nutritional factors on circulating melatonin. Ann N Y Acad Sci 719:146–158
Zurück zum Zitat Huether G, Poeggeler B, Reimer A, George A (1992) Effect of tryptophan administration on circulating melatonin levels in chicks and rats: evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract. Life Sci 51:945–953 Huether G, Poeggeler B, Reimer A, George A (1992) Effect of tryptophan administration on circulating melatonin levels in chicks and rats: evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract. Life Sci 51:945–953
Zurück zum Zitat Iguchi H, Kato KI, Ibayashi H (1982) Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis. J Clin Endocrinol Metab 54:1025–1027 Iguchi H, Kato KI, Ibayashi H (1982) Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis. J Clin Endocrinol Metab 54:1025–1027
Zurück zum Zitat Jean-Louis G, von Gizycki H, Zizi F (1998a) Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J Pineal Res 25:177–183 Jean-Louis G, von Gizycki H, Zizi F (1998a) Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J Pineal Res 25:177–183
Zurück zum Zitat Jean-Louis G, Zizi F, von Gizycki H, Taub H (1998b) Effects of melatonin in two individuals with Alzheimer’s disease. Percept Mot Skills 87:331–339 Jean-Louis G, Zizi F, von Gizycki H, Taub H (1998b) Effects of melatonin in two individuals with Alzheimer’s disease. Percept Mot Skills 87:331–339
Zurück zum Zitat Jiao S, Wu MM, Hu CL, Zhang ZH, Mei YA (2004) Melatonin receptor agonist 2-iodomelatonin prevents apoptosis of cerebellar granule neurons via K(+) current inhibition. J Pineal Res 36:109–116 Jiao S, Wu MM, Hu CL, Zhang ZH, Mei YA (2004) Melatonin receptor agonist 2-iodomelatonin prevents apoptosis of cerebellar granule neurons via K(+) current inhibition. J Pineal Res 36:109–116
Zurück zum Zitat Jimenez-Jorge S, Guerrero JM, Jimenez-Caliani AJ, Naranjo MC, Lardone PJ, Carrillo-Vico A, Osuna C, Molinero P (2007) Evidence for melatonin synthesis in the rat brain during development. J Pineal Res 42:240–246 Jimenez-Jorge S, Guerrero JM, Jimenez-Caliani AJ, Naranjo MC, Lardone PJ, Carrillo-Vico A, Osuna C, Molinero P (2007) Evidence for melatonin synthesis in the rat brain during development. J Pineal Res 42:240–246
Zurück zum Zitat Jiménez-Ortega V, Cano P, Scacchi PA, Cardinali DP, Esquifino AI (2011) Cadmium-induced disruption in 24-h expression of clock and redox enzyme genes in rat medial basal hypothalamus. Prevention by melatonin. Front Neurol 2:13 Jiménez-Ortega V, Cano P, Scacchi PA, Cardinali DP, Esquifino AI (2011) Cadmium-induced disruption in 24-h expression of clock and redox enzyme genes in rat medial basal hypothalamus. Prevention by melatonin. Front Neurol 2:13
Zurück zum Zitat Jin BK, Shin DY, Jeong MY, Gwag MR, Baik HW, Yoon KS, Cho YH, Joo WS, Kim YS, Baik HH (1998) Melatonin protects nigral dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity in rats. Neurosci Lett 245:61–64 Jin BK, Shin DY, Jeong MY, Gwag MR, Baik HW, Yoon KS, Cho YH, Joo WS, Kim YS, Baik HH (1998) Melatonin protects nigral dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity in rats. Neurosci Lett 245:61–64
Zurück zum Zitat Jonsson L, Ljunggren E, Bremer A, Pedersen C, Landen M, Thuresson K, Giacobini M, Melke J (2010) Mutation screening of melatonin-related genes in patients with autism spectrum disorders. BMC Med Genomics 3:10 Jonsson L, Ljunggren E, Bremer A, Pedersen C, Landen M, Thuresson K, Giacobini M, Melke J (2010) Mutation screening of melatonin-related genes in patients with autism spectrum disorders. BMC Med Genomics 3:10
Zurück zum Zitat Jou MJ (2011) Melatonin preserves the transient mitochondrial permeability transition for protection during mitochondrial Ca2+ stress in astrocyte. J Pineal Res 50:427–435 Jou MJ (2011) Melatonin preserves the transient mitochondrial permeability transition for protection during mitochondrial Ca2+ stress in astrocyte. J Pineal Res 50:427–435
Zurück zum Zitat Jucker M, Walker LC (2011) Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol 70:532–540 Jucker M, Walker LC (2011) Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol 70:532–540
Zurück zum Zitat Kabadi SV, Maher TJ (2010) Posttreatment with uridine and melatonin following traumatic brain injury reduces edema in various brain regions in rats. Ann N Y Acad Sci 1199:105–113 Kabadi SV, Maher TJ (2010) Posttreatment with uridine and melatonin following traumatic brain injury reduces edema in various brain regions in rats. Ann N Y Acad Sci 1199:105–113
Zurück zum Zitat Karasek M, Reiter RJ (2002) Melatonin and aging. Neuroendocrinol Lett 23(Suppl 1):14–16 Karasek M, Reiter RJ (2002) Melatonin and aging. Neuroendocrinol Lett 23(Suppl 1):14–16
Zurück zum Zitat Kaur C, Sivakumar V, Zhang Y, Ling EA (2006) Hypoxia-induced astrocytic reaction and increased vascular permeability in the rat cerebellum. Glia 54:826–839 Kaur C, Sivakumar V, Zhang Y, Ling EA (2006) Hypoxia-induced astrocytic reaction and increased vascular permeability in the rat cerebellum. Glia 54:826–839
Zurück zum Zitat Kaur C, Sivakumar V, Ling EA (2007) Expression of transferrin receptors in the pineal gland of postnatal and adult rats and its alteration in hypoxia and melatonin treatment. Glia 55:263–273 Kaur C, Sivakumar V, Ling EA (2007) Expression of transferrin receptors in the pineal gland of postnatal and adult rats and its alteration in hypoxia and melatonin treatment. Glia 55:263–273
Zurück zum Zitat Kaur C, Sivakumar V, Ling EA (2010) Melatonin protects periventricular white matter from damage due to hypoxia. J Pineal Res 48:185–193 Kaur C, Sivakumar V, Ling EA (2010) Melatonin protects periventricular white matter from damage due to hypoxia. J Pineal Res 48:185–193
Zurück zum Zitat Kaur C, Viswanathan S, Ling EA (2011) Hypoxia-induced cellular and vascular changes in the nucleus tractus solitarius and ventrolateral medulla. J Neuropathol Exp Neurol 70:201–217 Kaur C, Viswanathan S, Ling EA (2011) Hypoxia-induced cellular and vascular changes in the nucleus tractus solitarius and ventrolateral medulla. J Neuropathol Exp Neurol 70:201–217
Zurück zum Zitat Khandelwal PJ, Herman AM, Moussa CE (2011) Inflammation in the early stages of neurodegenerative pathology. J Neuroimmunol 238:1–11 Khandelwal PJ, Herman AM, Moussa CE (2011) Inflammation in the early stages of neurodegenerative pathology. J Neuroimmunol 238:1–11
Zurück zum Zitat Kilanczyk E, Bryszewska M (2003) The effect of melatonin on antioxidant enzymes in human diabetic skin fibroblasts. Cell Mol Biol Lett 8:333–336 Kilanczyk E, Bryszewska M (2003) The effect of melatonin on antioxidant enzymes in human diabetic skin fibroblasts. Cell Mol Biol Lett 8:333–336
Zurück zum Zitat Kilic E, Ozdemir YG, Bolay H, Kelestimur H, Dalkara T (1999) Pinealectomy aggravates and melatonin administration attenuates brain damage in focal ischemia. J Cereb Blood Flow Metab 19:511–516 Kilic E, Ozdemir YG, Bolay H, Kelestimur H, Dalkara T (1999) Pinealectomy aggravates and melatonin administration attenuates brain damage in focal ischemia. J Cereb Blood Flow Metab 19:511–516
Zurück zum Zitat Kilic U, Yilmaz B, Ugur M, Yuksel A, Reiter RJ, Hermann DM, Kilic E (2011) Evidence that membrane-bound G protein-coupled melatonin receptors MT1 and MT2 are not involved in the neuroprotective effects of melatonin in focal cerebral ischemia. J Pineal Res 52:228–235 Kilic U, Yilmaz B, Ugur M, Yuksel A, Reiter RJ, Hermann DM, Kilic E (2011) Evidence that membrane-bound G protein-coupled melatonin receptors MT1 and MT2 are not involved in the neuroprotective effects of melatonin in focal cerebral ischemia. J Pineal Res 52:228–235
Zurück zum Zitat Kitazawa M, Yamasaki TR, Laferla FM (2004) Microglia as a potential bridge between the amyloid {beta}-peptide and tau. Ann N Y Acad Sci 1035:85–103 Kitazawa M, Yamasaki TR, Laferla FM (2004) Microglia as a potential bridge between the amyloid {beta}-peptide and tau. Ann N Y Acad Sci 1035:85–103
Zurück zum Zitat Klein DC (2007) Arylalkylamine N-acetyltransferase: “the Timezyme”. J Biol Chem 282:4233–4237 Klein DC (2007) Arylalkylamine N-acetyltransferase: “the Timezyme”. J Biol Chem 282:4233–4237
Zurück zum Zitat Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275:1132–1136 Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275:1132–1136
Zurück zum Zitat Koh PO (2011) Melatonin prevents down-regulation of astrocytic phosphoprotein PEA-15 in ischemic brain injury. J Pineal Res 51:381–386 Koh PO (2011) Melatonin prevents down-regulation of astrocytic phosphoprotein PEA-15 in ischemic brain injury. J Pineal Res 51:381–386
Zurück zum Zitat Koh PO (2012) Melatonin attenuates decrease of protein phosphatase 2A subunit B in ischemic brain injury. J Pineal Res 52:57–61 Koh PO (2012) Melatonin attenuates decrease of protein phosphatase 2A subunit B in ischemic brain injury. J Pineal Res 52:57–61
Zurück zum Zitat Koller WC (1996) Management of motor fluctuations in Parkinson’s disease. Eur Neurol 36(Suppl 1):43–48 Koller WC (1996) Management of motor fluctuations in Parkinson’s disease. Eur Neurol 36(Suppl 1):43–48
Zurück zum Zitat Kunz D, Bes F (1997) Melatonin effects in a patient with severe REM sleep behavior disorder: case report and theoretical considerations. Neuropsychobiology 36:211–214 Kunz D, Bes F (1997) Melatonin effects in a patient with severe REM sleep behavior disorder: case report and theoretical considerations. Neuropsychobiology 36:211–214
Zurück zum Zitat Kunz D, Bes F (1999) Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord 14:507–511 Kunz D, Bes F (1999) Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord 14:507–511
Zurück zum Zitat Kvetnoy IM, Ingel IE, Kvetnaia TV, Malinovskaya NK, Rapoport SI, Raikhlin NT, Trofimov AV, Yuzhakov VV (2002) Gastrointestinal melatonin: cellular identification and biological role. Neuro Endocrinol Lett 23:121–132 Kvetnoy IM, Ingel IE, Kvetnaia TV, Malinovskaya NK, Rapoport SI, Raikhlin NT, Trofimov AV, Yuzhakov VV (2002) Gastrointestinal melatonin: cellular identification and biological role. Neuro Endocrinol Lett 23:121–132
Zurück zum Zitat Lacza Z, Horn TF, Snipes JA, Zhang J, Roychowdhury S, Horvath EM, Figueroa JP, Kollai M, Szabo C, Busija DW (2004) Lack of mitochondrial nitric oxide production in the mouse brain. J Neurochem 90:942–951 Lacza Z, Horn TF, Snipes JA, Zhang J, Roychowdhury S, Horvath EM, Figueroa JP, Kollai M, Szabo C, Busija DW (2004) Lack of mitochondrial nitric oxide production in the mouse brain. J Neurochem 90:942–951
Zurück zum Zitat Landau M, Zisapel N (2007) The low affinity binding of melatonin to calmodulin: use of computational methods to explain its physiological relevance. In: Cardinali DP, Pandi-Perumal SR (eds) Melatonin - From Molecules to Therapy. Nova Science, New York, pp 69–79 Landau M, Zisapel N (2007) The low affinity binding of melatonin to calmodulin: use of computational methods to explain its physiological relevance. In: Cardinali DP, Pandi-Perumal SR (eds) Melatonin - From Molecules to Therapy. Nova Science, New York, pp 69–79
Zurück zum Zitat Lardone PJ, Guerrero JM, Fernandez-Santos JM, Rubio A, Martin-Lacave I, Carrillo-Vico A (2011) Melatonin synthesized by T lymphocytes as a ligand of the retinoic acid-related orphan receptor. J Pineal Res 51:454–462 Lardone PJ, Guerrero JM, Fernandez-Santos JM, Rubio A, Martin-Lacave I, Carrillo-Vico A (2011) Melatonin synthesized by T lymphocytes as a ligand of the retinoic acid-related orphan receptor. J Pineal Res 51:454–462
Zurück zum Zitat Lee EJ, Wu TS, Lee MY, Chen TY, Tsai YY, Chuang JI, Chang GL (2004) Delayed treatment with melatonin enhances electrophysiological recovery following transient focal cerebral ischemia in rats. J Pineal Res 36:33–42 Lee EJ, Wu TS, Lee MY, Chen TY, Tsai YY, Chuang JI, Chang GL (2004) Delayed treatment with melatonin enhances electrophysiological recovery following transient focal cerebral ischemia in rats. J Pineal Res 36:33–42
Zurück zum Zitat León-Blanco MM, Guerrero JM, Reiter RJ, Pozo D (2004) RNA expression of human telomerase subunits TR and TERT is differentially affected by melatonin receptor agonists in the MCF-7 tumor cell line. Cancer Lett 216:73–80 León-Blanco MM, Guerrero JM, Reiter RJ, Pozo D (2004) RNA expression of human telomerase subunits TR and TERT is differentially affected by melatonin receptor agonists in the MCF-7 tumor cell line. Cancer Lett 216:73–80
Zurück zum Zitat Levoye A, Dam J, Ayoub MA, Guillaume JL, Couturier C, Delagrange P, Jockers R (2006) The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. EMBO J 25:3012–3023 Levoye A, Dam J, Ayoub MA, Guillaume JL, Couturier C, Delagrange P, Jockers R (2006) The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. EMBO J 25:3012–3023
Zurück zum Zitat Lewy AJ, Sack RA, Singer CL (1984) Assessment and treatment of chronobiologic disorders using plasma melatonin levels and bright light exposure: the clock-gate model and the phase response curve. Psychopharmacol Bull 20:561–565 Lewy AJ, Sack RA, Singer CL (1984) Assessment and treatment of chronobiologic disorders using plasma melatonin levels and bright light exposure: the clock-gate model and the phase response curve. Psychopharmacol Bull 20:561–565
Zurück zum Zitat Lezoualc’h F, Skutella T, Widmann M, Behl C (1996) Melatonin prevents oxidative stress-induced cell death in hippocampal cells. NeuroReport 7:2071–2077 Lezoualc’h F, Skutella T, Widmann M, Behl C (1996) Melatonin prevents oxidative stress-induced cell death in hippocampal cells. NeuroReport 7:2071–2077
Zurück zum Zitat Li XC, Wang ZF, Zhang JX, Wang Q, Wang JZ (2005) Effect of melatonin on calyculin A-induced tau hyperphosphorylation. Eur J Pharmacol 510:25–30 Li XC, Wang ZF, Zhang JX, Wang Q, Wang JZ (2005) Effect of melatonin on calyculin A-induced tau hyperphosphorylation. Eur J Pharmacol 510:25–30
Zurück zum Zitat Lieverse R, Van Someren EJ, Nielen MM, Uitdehaag BM, Smit JH, Hoogendijk WJ (2011) Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial. Arch Gen Psychiatry 68:61–70 Lieverse R, Van Someren EJ, Nielen MM, Uitdehaag BM, Smit JH, Hoogendijk WJ (2011) Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial. Arch Gen Psychiatry 68:61–70
Zurück zum Zitat Lin HW, Lee EJ (2009) Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages. Neuropsychiatr Dis Treat 5:157–162 Lin HW, Lee EJ (2009) Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages. Neuropsychiatr Dis Treat 5:157–162
Zurück zum Zitat Ling ZQ, Tian Q, Wang L, Fu ZQ, Wang XC, Wang Q, Wang JZ (2009) Constant illumination induces Alzheimer-like damages with endoplasmic reticulum involvement and the protection of melatonin. J Alzheimers Dis 16:287–300 Ling ZQ, Tian Q, Wang L, Fu ZQ, Wang XC, Wang Q, Wang JZ (2009) Constant illumination induces Alzheimer-like damages with endoplasmic reticulum involvement and the protection of melatonin. J Alzheimers Dis 16:287–300
Zurück zum Zitat Liu T, Borjigin J (2005) N-acetyltransferase is not the rate-limiting enzyme of melatonin synthesis at night. J Pineal Res 39:91–96 Liu T, Borjigin J (2005) N-acetyltransferase is not the rate-limiting enzyme of melatonin synthesis at night. J Pineal Res 39:91–96
Zurück zum Zitat Liu RY, Zhou JN, Van Heerikhuize J, Hofman MA, Swaab DF (1999) Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-ε 4/4 genotype. J Clin Endocrinol Metab 84:323–327 Liu RY, Zhou JN, Van Heerikhuize J, Hofman MA, Swaab DF (1999) Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-ε 4/4 genotype. J Clin Endocrinol Metab 84:323–327
Zurück zum Zitat Louzada PR, Paula Lima AC, Mendonca-Silva DL, Noel F, De Mello FG, Ferreira ST (2004) Taurine prevents the neurotoxicity of beta-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer’s disease and other neurological disorders. FASEB J 18:511–518 Louzada PR, Paula Lima AC, Mendonca-Silva DL, Noel F, De Mello FG, Ferreira ST (2004) Taurine prevents the neurotoxicity of beta-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer’s disease and other neurological disorders. FASEB J 18:511–518
Zurück zum Zitat Luboshitzky R, Shen-Orr Z, Tzischichinsky O, Maldonado M, Herer P, Lavie P (2001) Actigraphic sleep–wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer’s disease. Chronobiol Int 18:513–524 Luboshitzky R, Shen-Orr Z, Tzischichinsky O, Maldonado M, Herer P, Lavie P (2001) Actigraphic sleep–wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer’s disease. Chronobiol Int 18:513–524
Zurück zum Zitat Macias M, Escames G, León J, Coto A, Sbihi Y, Osuna A, Acuña-Castroviejo D (2003) Calreticulin–melatonin. An unexpected relationship. Eur J Biochem 270:832–840 Macias M, Escames G, León J, Coto A, Sbihi Y, Osuna A, Acuña-Castroviejo D (2003) Calreticulin–melatonin. An unexpected relationship. Eur J Biochem 270:832–840
Zurück zum Zitat Macleod MR, O’Collins T, Horky LL, Howells DW, Donnan GA (2005) Systematic review and meta-analysis of the efficacy of melatonin in experimental stroke. J Pineal Res 38:35–41 Macleod MR, O’Collins T, Horky LL, Howells DW, Donnan GA (2005) Systematic review and meta-analysis of the efficacy of melatonin in experimental stroke. J Pineal Res 38:35–41
Zurück zum Zitat Magri F, Sarra S, Cinchetti W, Guazzoni V, Fioravanti M, Cravello L, Ferrari E (2004) Qualitative and quantitative changes of melatonin levels in physiological and pathological aging and in centenarians. J Pineal Res 36:256–261 Magri F, Sarra S, Cinchetti W, Guazzoni V, Fioravanti M, Cravello L, Ferrari E (2004) Qualitative and quantitative changes of melatonin levels in physiological and pathological aging and in centenarians. J Pineal Res 36:256–261
Zurück zum Zitat Maguire-Zeiss KA, Federoff HJ (2010) Future directions for immune modulation in neurodegenerative disorders: focus on Parkinson’s disease. J Neural Transm 117:1019–1025 Maguire-Zeiss KA, Federoff HJ (2010) Future directions for immune modulation in neurodegenerative disorders: focus on Parkinson’s disease. J Neural Transm 117:1019–1025
Zurück zum Zitat Mahlberg R, Walther S (2007) Actigraphy in agitated patients with dementia: monitoring treatment outcomes. Z Gerontol Geriatr 40:178–184 Mahlberg R, Walther S (2007) Actigraphy in agitated patients with dementia: monitoring treatment outcomes. Z Gerontol Geriatr 40:178–184
Zurück zum Zitat Mahlberg R, Kunz D, Sutej I, Kuhl KP, Hellweg R (2004) Melatonin treatment of day–night rhythm disturbances and sundowning in Alzheimer disease: an open-label pilot study using actigraphy. J Clin Psychopharmacol 24:456–459 Mahlberg R, Kunz D, Sutej I, Kuhl KP, Hellweg R (2004) Melatonin treatment of day–night rhythm disturbances and sundowning in Alzheimer disease: an open-label pilot study using actigraphy. J Clin Psychopharmacol 24:456–459
Zurück zum Zitat Mahlberg R, Kienast T, Hadel S, Heidenreich JO, Schmitz S, Kunz D (2009) Degree of pineal calcification (DOC) is associated with polysomnographic sleep measures in primary insomnia patients. Sleep Med 10:439–445 Mahlberg R, Kienast T, Hadel S, Heidenreich JO, Schmitz S, Kunz D (2009) Degree of pineal calcification (DOC) is associated with polysomnographic sleep measures in primary insomnia patients. Sleep Med 10:439–445
Zurück zum Zitat Manev H, Uz T, Kharlamov A, Joo JY (1996) Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats. FASEB J 10:1546–1551 Manev H, Uz T, Kharlamov A, Joo JY (1996) Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats. FASEB J 10:1546–1551
Zurück zum Zitat Maronde E, Stehle JH (2007) The mammalian pineal gland: known facts, unknown facets. Trends Endocrinol Metab 18:142–149 Maronde E, Stehle JH (2007) The mammalian pineal gland: known facts, unknown facets. Trends Endocrinol Metab 18:142–149
Zurück zum Zitat Martin M, Macias M, Escames G, Reiter RJ, Agapito MT, Ortiz GG, Acuña-Castroviejo D (2000) Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res 28:242–248 Martin M, Macias M, Escames G, Reiter RJ, Agapito MT, Ortiz GG, Acuña-Castroviejo D (2000) Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res 28:242–248
Zurück zum Zitat Martin M, Macias M, León J, Escames G, Khaldy H, Acuña-Castroviejo D (2002) Melatonin increases the activity of the oxidative phosphorylation enzymes and the production of ATP in rat brain and liver mitochondria. Int J Biochem Cell Biol 34:348–357 Martin M, Macias M, León J, Escames G, Khaldy H, Acuña-Castroviejo D (2002) Melatonin increases the activity of the oxidative phosphorylation enzymes and the production of ATP in rat brain and liver mitochondria. Int J Biochem Cell Biol 34:348–357
Zurück zum Zitat Mathes AM, Kubulus D, Weiler J, Bentley A, Waibel L, Wolf B, Bauer I, Rensing H (2008) Melatonin receptors mediate improvements of liver function but not of hepatic perfusion and integrity after hemorrhagic shock in rats. Crit Care Med 36:24–29 Mathes AM, Kubulus D, Weiler J, Bentley A, Waibel L, Wolf B, Bauer I, Rensing H (2008) Melatonin receptors mediate improvements of liver function but not of hepatic perfusion and integrity after hemorrhagic shock in rats. Crit Care Med 36:24–29
Zurück zum Zitat Matsubara E, Bryant-Thomas T, Pacheco QJ, Henry TL, Poeggeler B, Herbert D, Cruz-Sanchez F, Chyan YJ, Smith MA, Perry G, Shoji M, Abe K, Leóne A, Grundke-Ikbal I, Wilson GL, Ghiso J, Williams C, Refolo LM, Pappolla MA, Chain DG, Neria E (2003) Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer’s disease. J Neurochem 85:1101–1108 Matsubara E, Bryant-Thomas T, Pacheco QJ, Henry TL, Poeggeler B, Herbert D, Cruz-Sanchez F, Chyan YJ, Smith MA, Perry G, Shoji M, Abe K, Leóne A, Grundke-Ikbal I, Wilson GL, Ghiso J, Williams C, Refolo LM, Pappolla MA, Chain DG, Neria E (2003) Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer’s disease. J Neurochem 85:1101–1108
Zurück zum Zitat Mayo JC, Sainz RM, Uria H, Antolin I, Esteban MM, Rodríguez C (1998) Melatonin prevents apoptosis induced by 6-hydroxydopamine in neuronal cells: implications for Parkinson’s disease. J Pineal Res 24:179–192 Mayo JC, Sainz RM, Uria H, Antolin I, Esteban MM, Rodríguez C (1998) Melatonin prevents apoptosis induced by 6-hydroxydopamine in neuronal cells: implications for Parkinson’s disease. J Pineal Res 24:179–192
Zurück zum Zitat Mazzoccoli G, De Cata A, Carughi S, Greco A, Inglese M, Perfetto F, Tarquini R (2010a) A possible mechanism for altered immune response in the elderly. In Vivo (Athens, Greece) 24:471–487 Mazzoccoli G, De Cata A, Carughi S, Greco A, Inglese M, Perfetto F, Tarquini R (2010a) A possible mechanism for altered immune response in the elderly. In Vivo (Athens, Greece) 24:471–487
Zurück zum Zitat Medeiros CA, Carvalhedo de Bruin PF, Lopes LA, Magalhaes MC, de Lourdes SM, Sales dBV (2007) Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson’s disease: a randomized, double blind, placebo-controlled study. J Neurol 254:459–464 Medeiros CA, Carvalhedo de Bruin PF, Lopes LA, Magalhaes MC, de Lourdes SM, Sales dBV (2007) Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson’s disease: a randomized, double blind, placebo-controlled study. J Neurol 254:459–464
Zurück zum Zitat Mediavilla MD, Sanchez-Barcelo EJ, Tan DX, Manchester L, Reiter RJ (2010) Basic mechanisms involved in the anti-cancer effects of melatonin. Curr Med Chem 17:4462–4481 Mediavilla MD, Sanchez-Barcelo EJ, Tan DX, Manchester L, Reiter RJ (2010) Basic mechanisms involved in the anti-cancer effects of melatonin. Curr Med Chem 17:4462–4481
Zurück zum Zitat Melchiorri D, Reiter RJ, Chen LD, Sewerynek E, Nistico G (1996) Melatonin affords protection against kainate-induced in vitro lipid peroxidation in brain. Eur J Pharmacol 305:239–242 Melchiorri D, Reiter RJ, Chen LD, Sewerynek E, Nistico G (1996) Melatonin affords protection against kainate-induced in vitro lipid peroxidation in brain. Eur J Pharmacol 305:239–242
Zurück zum Zitat Melke J, Goubran BH, Chaste P, Betancur C, Nygren G, Anckarsater H, Rastam M, Stahlberg O, Gillberg IC, Delorme R, Chabane N, Mouren-Simeoni MC, Fauchereau F, Durand CM, Chevalier F, Drouot X, Collet C, Launay JM, Leboyer M, Gillberg C, Bourgeron T (2008) Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry 13:90–98 Melke J, Goubran BH, Chaste P, Betancur C, Nygren G, Anckarsater H, Rastam M, Stahlberg O, Gillberg IC, Delorme R, Chabane N, Mouren-Simeoni MC, Fauchereau F, Durand CM, Chevalier F, Drouot X, Collet C, Launay JM, Leboyer M, Gillberg C, Bourgeron T (2008) Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry 13:90–98
Zurück zum Zitat Menéndez-Pelaez A, Reiter RJ (1993) Distribution of melatonin in mammalian tissues: the relative importance of nuclear versus cytosolic localization. J Pineal Res 15:59–69 Menéndez-Pelaez A, Reiter RJ (1993) Distribution of melatonin in mammalian tissues: the relative importance of nuclear versus cytosolic localization. J Pineal Res 15:59–69
Zurück zum Zitat Mesenge C, Margaill I, Verrecchia C, Allix M, Boulu RG, Plotkine M (1998) Protective effect of melatonin in a model of traumatic brain injury in mice. J Pineal Res 25:41–46 Mesenge C, Margaill I, Verrecchia C, Allix M, Boulu RG, Plotkine M (1998) Protective effect of melatonin in a model of traumatic brain injury in mice. J Pineal Res 25:41–46
Zurück zum Zitat Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, Rivet JM, Cussac D (2003) The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 306:954–964 Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, Rivet JM, Cussac D (2003) The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 306:954–964
Zurück zum Zitat Mishima K, Tozawa T, Satoh K, Matsumoto Y, Hishikawa Y, Okawa M (1999) Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer’s type with disturbed sleep-waking. Biol Psychiatry 45:417–421 Mishima K, Tozawa T, Satoh K, Matsumoto Y, Hishikawa Y, Okawa M (1999) Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer’s type with disturbed sleep-waking. Biol Psychiatry 45:417–421
Zurück zum Zitat Mishima K, Okawa M, Hozumi S, Hishikawa Y (2000) Supplementary administration of artificial bright light and melatonin as potent treatment for disorganized circadian rest-activity and dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly persons. Chronobiol Int 17:419–432 Mishima K, Okawa M, Hozumi S, Hishikawa Y (2000) Supplementary administration of artificial bright light and melatonin as potent treatment for disorganized circadian rest-activity and dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly persons. Chronobiol Int 17:419–432
Zurück zum Zitat Mishima K, Okawa M, Shimizu T, Hishikawa Y (2001) Diminished melatonin secretion in the elderly caused by insufficient environmental illumination. J Clin Endocrinol Metab 86:129–134 Mishima K, Okawa M, Shimizu T, Hishikawa Y (2001) Diminished melatonin secretion in the elderly caused by insufficient environmental illumination. J Clin Endocrinol Metab 86:129–134
Zurück zum Zitat Miyamoto M (2009) Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders. CNS Neurosci Ther 15:32–51 Miyamoto M (2009) Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders. CNS Neurosci Ther 15:32–51
Zurück zum Zitat Moller M, Baeres FM (2002) The anatomy and innervation of the mammalian pineal gland. Cell Tissue Res 309:139–150 Moller M, Baeres FM (2002) The anatomy and innervation of the mammalian pineal gland. Cell Tissue Res 309:139–150
Zurück zum Zitat Monti JM, Cardinali DP (2000) A critical assessment of the melatonin effect on sleep in humans. Biol Signals Recept 9:328–339 Monti JM, Cardinali DP (2000) A critical assessment of the melatonin effect on sleep in humans. Biol Signals Recept 9:328–339
Zurück zum Zitat Monti JM, Alvarino F, Cardinali DP, Savio I, Pintos A (1999) Polysomnographic study of the effect of melatonin on sleep in elderly patients with chronic primary insomnia. Arch Gerontol Geriatr 28:85–98 Monti JM, Alvarino F, Cardinali DP, Savio I, Pintos A (1999) Polysomnographic study of the effect of melatonin on sleep in elderly patients with chronic primary insomnia. Arch Gerontol Geriatr 28:85–98
Zurück zum Zitat Mukda S, Moller M, Ebadi M, Govitrapong P (2009) The modulatory effect of substance P on rat pineal norepinephrine release and melatonin secretion. Neurosci Lett 461:258–261 Mukda S, Moller M, Ebadi M, Govitrapong P (2009) The modulatory effect of substance P on rat pineal norepinephrine release and melatonin secretion. Neurosci Lett 461:258–261
Zurück zum Zitat Mulchahey JJ, Goldwater DR, Zemlan FP (2004) A single blind, placebo controlled, across groups dose escalation study of the safety, tolerability, pharmacokinetics and pharmacodynamics of the melatonin analog beta-methyl 6 chloromelatonin. Life Sci 75:1843–1856 Mulchahey JJ, Goldwater DR, Zemlan FP (2004) A single blind, placebo controlled, across groups dose escalation study of the safety, tolerability, pharmacokinetics and pharmacodynamics of the melatonin analog beta-methyl 6 chloromelatonin. Life Sci 75:1843–1856
Zurück zum Zitat Nag S, Kapadia A, Stewart DJ (2011) Review: molecular pathogenesis of blood-brain barrier breakdown in acute brain injury. Neuropathol Appl Neurobiol 37:3–23 Nag S, Kapadia A, Stewart DJ (2011) Review: molecular pathogenesis of blood-brain barrier breakdown in acute brain injury. Neuropathol Appl Neurobiol 37:3–23
Zurück zum Zitat Nakazawa T, Nakazawa C, Matsubara A, Noda K, Hisatomi T, She H, Michaud N, Hafezi-Moghadam A, Miller JW, Benowitz LI (2006) Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma. J Neurosci 26:12633–12641 Nakazawa T, Nakazawa C, Matsubara A, Noda K, Hisatomi T, She H, Michaud N, Hafezi-Moghadam A, Miller JW, Benowitz LI (2006) Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma. J Neurosci 26:12633–12641
Zurück zum Zitat Nosjean O, Ferro M, Coge F, Beauverger P, Henlin JM, Lefoulon F, Fauchere JL, Delagrange P, Canet E, Boutin JA (2000) Identification of the melatonin-binding site MT3 as the quinone reductase 2. J Biol Chem 275:31311–31317 Nosjean O, Ferro M, Coge F, Beauverger P, Henlin JM, Lefoulon F, Fauchere JL, Delagrange P, Canet E, Boutin JA (2000) Identification of the melatonin-binding site MT3 as the quinone reductase 2. J Biol Chem 275:31311–31317
Zurück zum Zitat Ohashi Y, Okamoto N, Uchida K, Iyo M, Mori N, Morita Y (1999) Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer’s type. Biol Psychiatry 45:1646–1652 Ohashi Y, Okamoto N, Uchida K, Iyo M, Mori N, Morita Y (1999) Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer’s type. Biol Psychiatry 45:1646–1652
Zurück zum Zitat Okatani Y, Wakatsuki A, Reiter RJ, Miyahara Y (2002) Hepatic mitochondrial dysfunction in senescence-accelerated mice: correction by long-term, orally administered physiological levels of melatonin. J Pineal Res 33:127–133 Okatani Y, Wakatsuki A, Reiter RJ, Miyahara Y (2002) Hepatic mitochondrial dysfunction in senescence-accelerated mice: correction by long-term, orally administered physiological levels of melatonin. J Pineal Res 33:127–133
Zurück zum Zitat Olanow CW (1990) Oxidation reactions in Parkinson’s disease. Neurology 40(Suppl):32–37 Olanow CW (1990) Oxidation reactions in Parkinson’s disease. Neurology 40(Suppl):32–37
Zurück zum Zitat Olanow CW (1992) An introduction to the free radical hypothesis in Parkinson’s disease. Ann Neurol 32(Suppl):S2–S9 Olanow CW (1992) An introduction to the free radical hypothesis in Parkinson’s disease. Ann Neurol 32(Suppl):S2–S9
Zurück zum Zitat Olanow CW, Brin MF, Obeso JA (2000) The role of deep brain stimulation as a surgical treatment for Parkinson’s disease. Neurology 55:S60–S66 Olanow CW, Brin MF, Obeso JA (2000) The role of deep brain stimulation as a surgical treatment for Parkinson’s disease. Neurology 55:S60–S66
Zurück zum Zitat Olcese JM, Cao C, Mori T, Mamcarz MB, Maxwell A, Runfeldt MJ, Wang L, Zhang C, Lin X, Zhang G, Arendash GW (2009) Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease. J Pineal Res 47:82–96 Olcese JM, Cao C, Mori T, Mamcarz MB, Maxwell A, Runfeldt MJ, Wang L, Zhang C, Lin X, Zhang G, Arendash GW (2009) Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease. J Pineal Res 47:82–96
Zurück zum Zitat Oliveira JM (2010) Nature and cause of mitochondrial dysfunction in Huntington’s disease: focusing on huntingtin and the striatum. J Neurochem 114:1–12 Oliveira JM (2010) Nature and cause of mitochondrial dysfunction in Huntington’s disease: focusing on huntingtin and the striatum. J Neurochem 114:1–12
Zurück zum Zitat Onuki J, Almeida EA, Medeiros MH, Di Mascio P (2005) Inhibition of 5-aminolevulinic acid-induced DNA damage by melatonin, N1-acetyl-N2-formyl-5-methoxykynuramine, quercetin or resveratrol. J Pineal Res 38:107–115 Onuki J, Almeida EA, Medeiros MH, Di Mascio P (2005) Inhibition of 5-aminolevulinic acid-induced DNA damage by melatonin, N1-acetyl-N2-formyl-5-methoxykynuramine, quercetin or resveratrol. J Pineal Res 38:107–115
Zurück zum Zitat Pablos MI, Reiter RJ, Chuang JI, Ortiz GG, Guerrero JM, Sewerynek E, Agapito MT, Melchiorri D, Lawrence R, Deneke SM (1997) Acutely administered melatonin reduces oxidative damage in lung and brain induced by hyperbaric oxygen. J Appl Physiol 83:354–358 Pablos MI, Reiter RJ, Chuang JI, Ortiz GG, Guerrero JM, Sewerynek E, Agapito MT, Melchiorri D, Lawrence R, Deneke SM (1997) Acutely administered melatonin reduces oxidative damage in lung and brain induced by hyperbaric oxygen. J Appl Physiol 83:354–358
Zurück zum Zitat Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424 Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424
Zurück zum Zitat Pagan C, Goubran-Botros H, Poirier K, Dumaine A, Jamain S, Moreno S, de Brouwer A, Van Esch H, Delorme R, Launay JM, Tzschach A, Kalscheuer VM, Lacombe D, Briault S, Laumonnier F, Raynaud M, van Bon BW, Willemsen MH, Leboyer M, Chelly J, Bourgeron T (2011) Mutation screening of ASMT, the last enzyme of the melatonin pathway, in a large sample of patients with Intellectual Disability. BMC Med Genet 12:17 Pagan C, Goubran-Botros H, Poirier K, Dumaine A, Jamain S, Moreno S, de Brouwer A, Van Esch H, Delorme R, Launay JM, Tzschach A, Kalscheuer VM, Lacombe D, Briault S, Laumonnier F, Raynaud M, van Bon BW, Willemsen MH, Leboyer M, Chelly J, Bourgeron T (2011) Mutation screening of ASMT, the last enzyme of the melatonin pathway, in a large sample of patients with Intellectual Disability. BMC Med Genet 12:17
Zurück zum Zitat Pandi-Perumal SR, Seils LK, Kayumov L, Ralph MR, Lowe A, Moller H, Swaab DF (2002) Senescence, sleep, and circadian rhythms. Ageing Res Rev 1:559–604 Pandi-Perumal SR, Seils LK, Kayumov L, Ralph MR, Lowe A, Moller H, Swaab DF (2002) Senescence, sleep, and circadian rhythms. Ageing Res Rev 1:559–604
Zurück zum Zitat Pandi-Perumal SR, Srinivasan V, Maestroni GJM, Cardinali DP, Poeggeler B, Hardeland R (2006) Melatonin: nature’s most versatile biological signal? FEBS J 273(13):2813–2838 Pandi-Perumal SR, Srinivasan V, Maestroni GJM, Cardinali DP, Poeggeler B, Hardeland R (2006) Melatonin: nature’s most versatile biological signal? FEBS J 273(13):2813–2838
Zurück zum Zitat Pappolla MA, Sos M, Omar RA, Bick RJ, Hickson-Bick DL, Reiter RJ, Efthimiopoulos S, Robakis NK (1997) Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide. J Neurosci 17:1683–1690 Pappolla MA, Sos M, Omar RA, Bick RJ, Hickson-Bick DL, Reiter RJ, Efthimiopoulos S, Robakis NK (1997) Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide. J Neurosci 17:1683–1690
Zurück zum Zitat Pappolla MA, Chyan YJ, Poeggeler B, Bozner P, Ghiso J, LeDoux SP, Wilson GL (1999) Alzheimer beta protein mediated oxidative damage of mitochondrial DNA: prevention by melatonin. J Pineal Res 27:226–229 Pappolla MA, Chyan YJ, Poeggeler B, Bozner P, Ghiso J, LeDoux SP, Wilson GL (1999) Alzheimer beta protein mediated oxidative damage of mitochondrial DNA: prevention by melatonin. J Pineal Res 27:226–229
Zurück zum Zitat Pappolla MA, Chyan YJ, Poeggeler B, Frangione B, Wilson G, Ghiso J, Reiter RJ (2000) An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer’s disease. J Neural Transm 107:203–231 Pappolla MA, Chyan YJ, Poeggeler B, Frangione B, Wilson G, Ghiso J, Reiter RJ (2000) An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer’s disease. J Neural Transm 107:203–231
Zurück zum Zitat Payton A, Miyajima F, Ollier W, Rabbitt P, Pickles A, Weiss V, Pendleton N, Horan M (2010) Investigation of a functional quinine oxidoreductase (NQO2) polymorphism and cognitive decline. Neurobiol Aging 31:351–352 Payton A, Miyajima F, Ollier W, Rabbitt P, Pickles A, Weiss V, Pendleton N, Horan M (2010) Investigation of a functional quinine oxidoreductase (NQO2) polymorphism and cognitive decline. Neurobiol Aging 31:351–352
Zurück zum Zitat Peck JS, LeGoff DB, Ahmed I, Goebert D (2004) Cognitive effects of exogenous melatonin administration in elderly persons: a pilot study. Am J Geriatr Psychiatry 12:432–436 Peck JS, LeGoff DB, Ahmed I, Goebert D (2004) Cognitive effects of exogenous melatonin administration in elderly persons: a pilot study. Am J Geriatr Psychiatry 12:432–436
Zurück zum Zitat Pei Z, Cheung RT (2004) Pretreatment with melatonin exerts anti-inflammatory effects against ischemia/reperfusion injury in a rat middle cerebral artery occlusion stroke model. J Pineal Res 37:85–91 Pei Z, Cheung RT (2004) Pretreatment with melatonin exerts anti-inflammatory effects against ischemia/reperfusion injury in a rat middle cerebral artery occlusion stroke model. J Pineal Res 37:85–91
Zurück zum Zitat Peng TI, Hsiao CW, Reiter RJ, Tanaka M, Lai YK, Jou MJ (2012) mtDNA T8993G mutation-induced mitochondrial complex V inhibition augments cardiolipin-dependent alterations in mitochondrial dynamics during oxidative, Ca2+, and lipid insults in NARP cybrids: a potential therapeutic target for melatonin. J Pineal Res 52:93–106 Peng TI, Hsiao CW, Reiter RJ, Tanaka M, Lai YK, Jou MJ (2012) mtDNA T8993G mutation-induced mitochondrial complex V inhibition augments cardiolipin-dependent alterations in mitochondrial dynamics during oxidative, Ca2+, and lipid insults in NARP cybrids: a potential therapeutic target for melatonin. J Pineal Res 52:93–106
Zurück zum Zitat Perez M, Hernandez F, Gomez-Ramos A, Smith M, Perry G, Avila J (2002) Formation of aberrant phosphotau fibrillar polymers in neural cultured cells. Eur J Biochem 269:1484–1489 Perez M, Hernandez F, Gomez-Ramos A, Smith M, Perry G, Avila J (2002) Formation of aberrant phosphotau fibrillar polymers in neural cultured cells. Eur J Biochem 269:1484–1489
Zurück zum Zitat Poeggeler B, Miravalle L, Zagorski MG, Wisniewski T, Chyan YJ, Zhang Y, Shao H, Bryant-Thomas T, Vidal R, Frangione B, Ghiso J, Pappolla MA (2001) Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Aβ peptide. Biochemistry 40:14995–15001 Poeggeler B, Miravalle L, Zagorski MG, Wisniewski T, Chyan YJ, Zhang Y, Shao H, Bryant-Thomas T, Vidal R, Frangione B, Ghiso J, Pappolla MA (2001) Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Aβ peptide. Biochemistry 40:14995–15001
Zurück zum Zitat Poliandri AH, Esquifino AI, Cano P, Jimenez V, Lafuente A, Cardinali DP, Duvilanski BH (2006) In vivo protective effect of melatonin on cadmium-induced changes in redox balance and gene expression in rat hypothalamus and anterior pituitary. J Pineal Res 41:238–246 Poliandri AH, Esquifino AI, Cano P, Jimenez V, Lafuente A, Cardinali DP, Duvilanski BH (2006) In vivo protective effect of melatonin on cadmium-induced changes in redox balance and gene expression in rat hypothalamus and anterior pituitary. J Pineal Res 41:238–246
Zurück zum Zitat Princ FG, Juknat AA, Maxit AG, Cardalda C, Batlle A (1997) Melatonin’s antioxidant protection against delta-aminolevulinic acid-induced oxidative damage in rat cerebellum. J Pineal Res 23:40–46 Princ FG, Juknat AA, Maxit AG, Cardalda C, Batlle A (1997) Melatonin’s antioxidant protection against delta-aminolevulinic acid-induced oxidative damage in rat cerebellum. J Pineal Res 23:40–46
Zurück zum Zitat Quinn J, Kulhanek D, Nowlin J, Jones R, Pratico D, Rokach J, Stackman R (2005) Chronic melatonin therapy fails to alter amyloid burden or oxidative damage in old Tg2576 mice: implications for clinical trials. Brain Res 1037:209–213 Quinn J, Kulhanek D, Nowlin J, Jones R, Pratico D, Rokach J, Stackman R (2005) Chronic melatonin therapy fails to alter amyloid burden or oxidative damage in old Tg2576 mice: implications for clinical trials. Brain Res 1037:209–213
Zurück zum Zitat Radogna F, Diederich M, Ghibelli L (2010) Melatonin: a pleiotropic molecule regulating inflammation. Biochem Pharmacol 80:1844–1852 Radogna F, Diederich M, Ghibelli L (2010) Melatonin: a pleiotropic molecule regulating inflammation. Biochem Pharmacol 80:1844–1852
Zurück zum Zitat Rajaratnam SM, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, Klerman EB (2009) Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials. Lancet 373:482–491 Rajaratnam SM, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, Klerman EB (2009) Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials. Lancet 373:482–491
Zurück zum Zitat Reiter RJ (1980) The pineal and its hormones in the control of reproduction in mammals. Endocr Rev 1:109–131 Reiter RJ (1980) The pineal and its hormones in the control of reproduction in mammals. Endocr Rev 1:109–131
Zurück zum Zitat Reiter RJ (1998) Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol 56:359–384 Reiter RJ (1998) Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol 56:359–384
Zurück zum Zitat Reiter RJ, Tan DX (2003) What constitutes a physiological concentration of melatonin? J Pineal Res 34:79–80 Reiter RJ, Tan DX (2003) What constitutes a physiological concentration of melatonin? J Pineal Res 34:79–80
Zurück zum Zitat Reiter RJ, Manchester LC, Tan DX (2010) Neurotoxins: free radical mechanisms and melatonin protection. Curr Neuropharmacol 8:194–210 Reiter RJ, Manchester LC, Tan DX (2010) Neurotoxins: free radical mechanisms and melatonin protection. Curr Neuropharmacol 8:194–210
Zurück zum Zitat Reyes Toso C, Ricci C, de Mignone IR, Reyes P, Linares LM, Albornoz LE, Cardinali DP, Zaninovich AA (2003) In vitro effect of melatonin on oxygen consumption in liver mitochondria of rats. Neuroendocrinol Lett 24:341–344 Reyes Toso C, Ricci C, de Mignone IR, Reyes P, Linares LM, Albornoz LE, Cardinali DP, Zaninovich AA (2003) In vitro effect of melatonin on oxygen consumption in liver mitochondria of rats. Neuroendocrinol Lett 24:341–344
Zurück zum Zitat Ribelayga C, Pévet P, Simonneaux V (2000) HIOMT drives the photoperiodic changes in the amplitude of the melatonin peak of the Siberian hamster. Am J Physiol Regul Integr Comp Physiol 278:R1339–R1345 Ribelayga C, Pévet P, Simonneaux V (2000) HIOMT drives the photoperiodic changes in the amplitude of the melatonin peak of the Siberian hamster. Am J Physiol Regul Integr Comp Physiol 278:R1339–R1345
Zurück zum Zitat Riemersma-van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, van Someren EJ (2008) Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA 299:2642–2655 Riemersma-van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, van Someren EJ (2008) Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA 299:2642–2655
Zurück zum Zitat Rod NH, Hansen J, Schernhammer E, Ritz B (2010) Major life events and risk of Parkinson’s disease. Mov Disord 25:1639–1645 Rod NH, Hansen J, Schernhammer E, Ritz B (2010) Major life events and risk of Parkinson’s disease. Mov Disord 25:1639–1645
Zurück zum Zitat Rodríguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36:1–9 Rodríguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36:1–9
Zurück zum Zitat Rosales-Corral S, Tan DX, Reiter RJ, Valdivia-Velazquez M, Martinez-Barboza G, Acosta-Martinez JP, Ortiz GG (2003) Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid-beta peptide in rat brain: a comparative, in vivo study versus vitamin C and E. J Pineal Res 35:80–84 Rosales-Corral S, Tan DX, Reiter RJ, Valdivia-Velazquez M, Martinez-Barboza G, Acosta-Martinez JP, Ortiz GG (2003) Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid-beta peptide in rat brain: a comparative, in vivo study versus vitamin C and E. J Pineal Res 35:80–84
Zurück zum Zitat Rosen R, Hu DN, Perez V, Tai K, Yu GP, Chen M, Tone P, McCormick SA, Walsh J (2009) Urinary 6-sulfatoxymelatonin level in age-related macular degeneration patients. Mol Vis 15:1673–1679 Rosen R, Hu DN, Perez V, Tai K, Yu GP, Chen M, Tone P, McCormick SA, Walsh J (2009) Urinary 6-sulfatoxymelatonin level in age-related macular degeneration patients. Mol Vis 15:1673–1679
Zurück zum Zitat Rosenstein RE, Pandi-Perumal SR, Srinivasan V, Spence DW, Brown GM, Cardinali DP (2010) Melatonin as a therapeutic tool in ophthalmology: implication for glaucoma and uveitis. J Pineal Res 49:1–13 Rosenstein RE, Pandi-Perumal SR, Srinivasan V, Spence DW, Brown GM, Cardinali DP (2010) Melatonin as a therapeutic tool in ophthalmology: implication for glaucoma and uveitis. J Pineal Res 49:1–13
Zurück zum Zitat Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Davenport Y, Mueller PS, Newsome DA, Wehr TA (1984) Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry 41:72–80 Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Davenport Y, Mueller PS, Newsome DA, Wehr TA (1984) Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry 41:72–80
Zurück zum Zitat Sack RL, Lewy AJ, Erb DL, Vollmer WM, Singer CM (1986) Human melatonin production decreases with age. J Pineal Res 3:379–388 Sack RL, Lewy AJ, Erb DL, Vollmer WM, Singer CM (1986) Human melatonin production decreases with age. J Pineal Res 3:379–388
Zurück zum Zitat Sainz RM, Mayo JC, Rodríguez C, Tan DX, Lopez-Burillo S, Reiter RJ (2003) Melatonin and cell death: differential actions on apoptosis in normal and cancer cells. Cell Mol Life Sci 60:1407–1426 Sainz RM, Mayo JC, Rodríguez C, Tan DX, Lopez-Burillo S, Reiter RJ (2003) Melatonin and cell death: differential actions on apoptosis in normal and cancer cells. Cell Mol Life Sci 60:1407–1426
Zurück zum Zitat Saravanan KS, Sindhu KM, Mohanakumar KP (2007) Melatonin protects against rotenone-induced oxidative stress in a hemiparkinsonian rat model. J Pineal Res 42:247–253 Saravanan KS, Sindhu KM, Mohanakumar KP (2007) Melatonin protects against rotenone-induced oxidative stress in a hemiparkinsonian rat model. J Pineal Res 42:247–253
Zurück zum Zitat Savaskan E, Ayoub MA, Ravid R, Angeloni D, Fraschini F, Meier F, Eckert A, Muller-Spahn F, Jockers R (2005) Reduced hippocampal MT2 melatonin receptor expression in Alzheimer’s disease. J Pineal Res 38:10–16 Savaskan E, Ayoub MA, Ravid R, Angeloni D, Fraschini F, Meier F, Eckert A, Muller-Spahn F, Jockers R (2005) Reduced hippocampal MT2 melatonin receptor expression in Alzheimer’s disease. J Pineal Res 38:10–16
Zurück zum Zitat Scheer FA, Van Montfrans GA, Van Someren EJ, Mairuhu G, Buijs RM (2004) Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 43:192–197 Scheer FA, Van Montfrans GA, Van Someren EJ, Mairuhu G, Buijs RM (2004) Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 43:192–197
Zurück zum Zitat Scher J, Wankiewicz E, Brown GM, Fujieda H (2003) AII amacrine cells express the MT1 melatonin receptor in human and macaque retina. Exp Eye Res 77:375–382 Scher J, Wankiewicz E, Brown GM, Fujieda H (2003) AII amacrine cells express the MT1 melatonin receptor in human and macaque retina. Exp Eye Res 77:375–382
Zurück zum Zitat Schernhammer E, Chen H, Ritz B (2006) Circulating melatonin levels: possible link between Parkinson’s disease and cancer risk? Cancer Causes Control 17:577–582 Schernhammer E, Chen H, Ritz B (2006) Circulating melatonin levels: possible link between Parkinson’s disease and cancer risk? Cancer Causes Control 17:577–582
Zurück zum Zitat Serfaty M, Kennell-Webb S, Warner J, Blizard R, Raven P (2002) Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementia. Int J Geriatr Psychiatry 17:1120–1127 Serfaty M, Kennell-Webb S, Warner J, Blizard R, Raven P (2002) Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementia. Int J Geriatr Psychiatry 17:1120–1127
Zurück zum Zitat Shaikh AY, Xu J, Wu Y, He L, Hsu CY (1997) Melatonin protects bovine cerebral endothelial cells from hyperoxia-induced DNA damage and death. Neurosci Lett 229:193–197 Shaikh AY, Xu J, Wu Y, He L, Hsu CY (1997) Melatonin protects bovine cerebral endothelial cells from hyperoxia-induced DNA damage and death. Neurosci Lett 229:193–197
Zurück zum Zitat Siegrist C, Benedetti C, Orlando A, Beltran JM, Tuchscherr L, Noseda CM, Brusco LI, Cardinali DP (2001) Lack of changes in serum prolactin, FSH, TSH, and estradiol after melatonin treatment in doses that improve sleep and reduce benzodiazepine consumption in sleep-disturbed, middle-aged, and elderly patients. J Pineal Res 30:34–42 Siegrist C, Benedetti C, Orlando A, Beltran JM, Tuchscherr L, Noseda CM, Brusco LI, Cardinali DP (2001) Lack of changes in serum prolactin, FSH, TSH, and estradiol after melatonin treatment in doses that improve sleep and reduce benzodiazepine consumption in sleep-disturbed, middle-aged, and elderly patients. J Pineal Res 30:34–42
Zurück zum Zitat Silva SO, Rodrigues MR, Carvalho SR, Catalani LH, Campa A, Ximenes VF (2004) Oxidation of melatonin and its catabolites, N1-acetyl-N2-formyl-5-methoxykynuramine and N1-acetyl-5-methoxykynuramine, by activated leukocytes. J Pineal Res 37:171–175 Silva SO, Rodrigues MR, Carvalho SR, Catalani LH, Campa A, Ximenes VF (2004) Oxidation of melatonin and its catabolites, N1-acetyl-N2-formyl-5-methoxykynuramine and N1-acetyl-5-methoxykynuramine, by activated leukocytes. J Pineal Res 37:171–175
Zurück zum Zitat Simonneaux V, Ribelayga C (2003) Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev 55:325–395 Simonneaux V, Ribelayga C (2003) Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev 55:325–395
Zurück zum Zitat Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M, Thomas R, Thal LJ (2003) A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer’s disease. Sleep 26:893–901 Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M, Thomas R, Thal LJ (2003) A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer’s disease. Sleep 26:893–901
Zurück zum Zitat Singhal NK, Srivastava G, Patel DK, Jain SK, Singh MP (2011) Melatonin or silymarin reduces maneb- and paraquat-induced Parkinson’s disease phenotype in the mouse. J Pineal Res 50:97–109 Singhal NK, Srivastava G, Patel DK, Jain SK, Singh MP (2011) Melatonin or silymarin reduces maneb- and paraquat-induced Parkinson’s disease phenotype in the mouse. J Pineal Res 50:97–109
Zurück zum Zitat Skene DJ, Swaab DF (2003) Melatonin rhythmicity: effect of age and Alzheimer’s disease. Exp Gerontol 38:199–206 Skene DJ, Swaab DF (2003) Melatonin rhythmicity: effect of age and Alzheimer’s disease. Exp Gerontol 38:199–206
Zurück zum Zitat Skene DJ, Vivien-Roels B, Sparks DL, Hunsaker JC, Pévet P, Ravid D, Swaab DF (1990) Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer’s disease. Brain Res 528:170–174 Skene DJ, Vivien-Roels B, Sparks DL, Hunsaker JC, Pévet P, Ravid D, Swaab DF (1990) Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer’s disease. Brain Res 528:170–174
Zurück zum Zitat Southgate G, Daya S (1999) Melatonin reduces quinolinic acid-induced lipid peroxidation in rat brain homogenate. Metab Brain Dis 14:165–171 Southgate G, Daya S (1999) Melatonin reduces quinolinic acid-induced lipid peroxidation in rat brain homogenate. Metab Brain Dis 14:165–171
Zurück zum Zitat Spadoni G, Bedini A, Rivara S, Mor M (2011) Melatonin receptor agonists: new options for insomnia and depression treatment. CNS Neurosci Ther 17:733–741 Spadoni G, Bedini A, Rivara S, Mor M (2011) Melatonin receptor agonists: new options for insomnia and depression treatment. CNS Neurosci Ther 17:733–741
Zurück zum Zitat Spuch C, Antequera D, Isabel Fernandez-Bachiller M, Isabel Rodríguez-Franco M, Carro E (2010) A new tacrine-melatonin hybrid reduces amyloid burden and behavioral deficits in a mouse model of Alzheimer’s disease. Neurotox Res 17:421–431 Spuch C, Antequera D, Isabel Fernandez-Bachiller M, Isabel Rodríguez-Franco M, Carro E (2010) A new tacrine-melatonin hybrid reduces amyloid burden and behavioral deficits in a mouse model of Alzheimer’s disease. Neurotox Res 17:421–431
Zurück zum Zitat Srinivasan V, Singh J, Pandi-Perumal SR, Brown GM, Spence DW, Cardinali DP (2010) Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs. Adv Ther 27:796–813 Srinivasan V, Singh J, Pandi-Perumal SR, Brown GM, Spence DW, Cardinali DP (2010) Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs. Adv Ther 27:796–813
Zurück zum Zitat Srinivasan V, Spence DW, Pandi-Perumal SR, Brown GM (2011) Cardinali DP (2011) Melatonin in mitochondrial dysfunction and related disorders. Int J Alzheimer′s Dis vol. doi:10.4061/2011/741974 Srinivasan V, Spence DW, Pandi-Perumal SR, Brown GM (2011) Cardinali DP (2011) Melatonin in mitochondrial dysfunction and related disorders. Int J Alzheimer′s Dis vol. doi:10.​4061/​2011/​741974
Zurück zum Zitat Sterniczuk R, Dyck RH, Laferla FM, Antle MC (2010) Characterization of the 3xTg-AD mouse model of Alzheimer’s disease: part 1. Circadian changes. Brain Res 1348:139–148 Sterniczuk R, Dyck RH, Laferla FM, Antle MC (2010) Characterization of the 3xTg-AD mouse model of Alzheimer’s disease: part 1. Circadian changes. Brain Res 1348:139–148
Zurück zum Zitat Stevens RG, Hansen J, Costa G, Haus E, Kauppinen T, Aronson KJ, Castano-Vinyals G, Davis S, Frings-Dresen MH, Fritschi L, Kogevinas M, Kogi K, Lie JA, Lowden A, Peplonska B, Pesch B, Pukkala E, Schernhammer E, Travis RC, Vermeulen R, Zheng T, Cogliano V, Straif K (2011) Considerations of circadian impact for defining ‘shift work’ in cancer studies: IARC Working Group Report. Occup Environ Med 68:154–162 Stevens RG, Hansen J, Costa G, Haus E, Kauppinen T, Aronson KJ, Castano-Vinyals G, Davis S, Frings-Dresen MH, Fritschi L, Kogevinas M, Kogi K, Lie JA, Lowden A, Peplonska B, Pesch B, Pukkala E, Schernhammer E, Travis RC, Vermeulen R, Zheng T, Cogliano V, Straif K (2011) Considerations of circadian impact for defining ‘shift work’ in cancer studies: IARC Working Group Report. Occup Environ Med 68:154–162
Zurück zum Zitat Stopa EG, Volicer L, Kuo-Leblanc V, Harper D, Lathi D, Tate B, Satlin A (1999) Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia. J Neuropathol Exp Neurol 58:29–39 Stopa EG, Volicer L, Kuo-Leblanc V, Harper D, Lathi D, Tate B, Satlin A (1999) Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia. J Neuropathol Exp Neurol 58:29–39
Zurück zum Zitat Subramanian P, Mirunalini S, Pandi-Perumal SR, Trakht I, Cardinali DP (2007) Melatonin treatment improves the antioxidant status and decreases lipid content in brain and liver of rats. Eur J Pharmacol 571:116–119 Subramanian P, Mirunalini S, Pandi-Perumal SR, Trakht I, Cardinali DP (2007) Melatonin treatment improves the antioxidant status and decreases lipid content in brain and liver of rats. Eur J Pharmacol 571:116–119
Zurück zum Zitat Swabb DF, Fliers E, Partiman TS (1985) The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res 342:37–44 Swabb DF, Fliers E, Partiman TS (1985) The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res 342:37–44
Zurück zum Zitat Swerdlow RH (2011) Brain aging, Alzheimer’s disease, and mitochondria. Biochim Biophys Acta 1812:1630–1639 Swerdlow RH (2011) Brain aging, Alzheimer’s disease, and mitochondria. Biochim Biophys Acta 1812:1630–1639
Zurück zum Zitat Synofzik M, Ronchi D, Keskin I, Basak AN, Wilhelm C, Gobbi C, Birve A, Biskup S, Zecca C, Fernandez-Santiago R, Kaugesaar T, Schols L, Marklund SL, Andersen PM (2012) Mutant superoxide dismutase-1 indistinguishable from wild type causes ALS. Hum Mol Genet. http://dx.doi.org/10.1093/hmg/dds188 Synofzik M, Ronchi D, Keskin I, Basak AN, Wilhelm C, Gobbi C, Birve A, Biskup S, Zecca C, Fernandez-Santiago R, Kaugesaar T, Schols L, Marklund SL, Andersen PM (2012) Mutant superoxide dismutase-1 indistinguishable from wild type causes ALS. Hum Mol Genet. http://​dx.​doi.​org/​10.​1093/​hmg/​dds188
Zurück zum Zitat Tai SH, Hung YC, Lee EJ, Lee AC, Chen TY, Shen CC, Chen HY, Lee MY, Huang SY, Wu TS (2011) Melatonin protects against transient focal cerebral ischemia in both reproductively active and estrogen-deficient female rats: the impact of circulating estrogen on its hormetic dose-response. J Pineal Res 50:292–303 Tai SH, Hung YC, Lee EJ, Lee AC, Chen TY, Shen CC, Chen HY, Lee MY, Huang SY, Wu TS (2011) Melatonin protects against transient focal cerebral ischemia in both reproductively active and estrogen-deficient female rats: the impact of circulating estrogen on its hormetic dose-response. J Pineal Res 50:292–303
Zurück zum Zitat Takeuchi N, Uchimura N, Hashizume Y, Mukai M, Etoh Y, Yamamoto K, Kotorii T, Ohshima H, Ohshima M, Maeda H (2001) Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci 55:267–269 Takeuchi N, Uchimura N, Hashizume Y, Mukai M, Etoh Y, Yamamoto K, Kotorii T, Ohshima H, Ohshima M, Maeda H (2001) Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci 55:267–269
Zurück zum Zitat Tan DX, Manchester LC, Reiter RJ, Plummer BF, Hardies LJ, Weintraub ST, Vijayalaxmi Shepherd AM (1998) A novel melatonin metabolite, cyclic 3-hydroxymelatonin: a biomarker of in vivo hydroxyl radical generation. Biochem Biophys Res Commun 253:614–620 Tan DX, Manchester LC, Reiter RJ, Plummer BF, Hardies LJ, Weintraub ST, Vijayalaxmi Shepherd AM (1998) A novel melatonin metabolite, cyclic 3-hydroxymelatonin: a biomarker of in vivo hydroxyl radical generation. Biochem Biophys Res Commun 253:614–620
Zurück zum Zitat Tan D, Manchester LC, Reiter RJ, Qi W, Hanes MA, Farley NJ (1999) High physiological levels of melatonin in the bile of mammals. Life Sci 65:2523–2529 Tan D, Manchester LC, Reiter RJ, Qi W, Hanes MA, Farley NJ (1999) High physiological levels of melatonin in the bile of mammals. Life Sci 65:2523–2529
Zurück zum Zitat Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, Mayo JC, Sainz RM, Reiter RJ (2003) Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res 34:75–78 Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, Mayo JC, Sainz RM, Reiter RJ (2003) Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res 34:75–78
Zurück zum Zitat Tan DX, Manchester LC, Sanchez-Barcelo E, Mediavilla MD, Reiter RJ (2010) Significance of high levels of endogenous melatonin in mammalian cerebrospinal fluid and in the central nervous system. Curr Neuropharmacol 8:162–167 Tan DX, Manchester LC, Sanchez-Barcelo E, Mediavilla MD, Reiter RJ (2010) Significance of high levels of endogenous melatonin in mammalian cerebrospinal fluid and in the central nervous system. Curr Neuropharmacol 8:162–167
Zurück zum Zitat Tansey MG, McCoy MK, Frank-Cannon TC (2007) Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 208:1–25 Tansey MG, McCoy MK, Frank-Cannon TC (2007) Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 208:1–25
Zurück zum Zitat Tapias V, Cannon JR, Greenamyre JT (2010) Melatonin treatment potentiates neurodegeneration in a rat rotenone Parkinson’s disease model. J Neurosci Res 88:420–427 Tapias V, Cannon JR, Greenamyre JT (2010) Melatonin treatment potentiates neurodegeneration in a rat rotenone Parkinson’s disease model. J Neurosci Res 88:420–427
Zurück zum Zitat Taysi S, Memisogullari R, Koc M, Yazici AT, Aslankurt M, Gumustekin K, Al B, Ozabacigil F, Yilmaz A, Tahsin OH (2008) Melatonin reduces oxidative stress in the rat lens due to radiation-induced oxidative injury. Int J Radiat Biol 84:803–808 Taysi S, Memisogullari R, Koc M, Yazici AT, Aslankurt M, Gumustekin K, Al B, Ozabacigil F, Yilmaz A, Tahsin OH (2008) Melatonin reduces oxidative stress in the rat lens due to radiation-induced oxidative injury. Int J Radiat Biol 84:803–808
Zurück zum Zitat Thomas B, Mohanakumar KP (2004) Melatonin protects against oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum. J Pineal Res 36:25–32 Thomas B, Mohanakumar KP (2004) Melatonin protects against oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum. J Pineal Res 36:25–32
Zurück zum Zitat Travis RC, Allen NE, Peeters PH, van Noord PA, Key TJ (2003) Reproducibility over 5 years of measurements of 6-sulphatoxymelatonin in urine samples from postmenopausal women. Cancer Epidemiol Biomarkers Prev 12:806–808 Travis RC, Allen NE, Peeters PH, van Noord PA, Key TJ (2003) Reproducibility over 5 years of measurements of 6-sulphatoxymelatonin in urine samples from postmenopausal women. Cancer Epidemiol Biomarkers Prev 12:806–808
Zurück zum Zitat Tricoire H, Locatelli A, Chemineau P, Malpaux B (2002) Melatonin enters the cerebrospinal fluid through the pineal recess. Endocrinology 143:84–90 Tricoire H, Locatelli A, Chemineau P, Malpaux B (2002) Melatonin enters the cerebrospinal fluid through the pineal recess. Endocrinology 143:84–90
Zurück zum Zitat Tsai MC, Chen WJ, Tsai MS, Ching CH, Chuang JI (2011) Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats. J Pineal Res 51:233–245 Tsai MC, Chen WJ, Tsai MS, Ching CH, Chuang JI (2011) Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats. J Pineal Res 51:233–245
Zurück zum Zitat Tunez I, Montilla P, Del Carmen MM, Feijoo M, Salcedo M (2004) Protective effect of melatonin on 3-nitropropionic acid-induced oxidative stress in synaptosomes in an animal model of Huntington’s disease. J Pineal Res 37:252–256 Tunez I, Montilla P, Del Carmen MM, Feijoo M, Salcedo M (2004) Protective effect of melatonin on 3-nitropropionic acid-induced oxidative stress in synaptosomes in an animal model of Huntington’s disease. J Pineal Res 37:252–256
Zurück zum Zitat Turek FW, Gillette MU (2004) Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists. Sleep Med 5:523–532 Turek FW, Gillette MU (2004) Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists. Sleep Med 5:523–532
Zurück zum Zitat Uchida K, Okamoto N, Ohara K, Morita Y (1996) Daily rhythm of serum melatonin in patients with dementia of the degenerate type. Brain Res 717:154–159 Uchida K, Okamoto N, Ohara K, Morita Y (1996) Daily rhythm of serum melatonin in patients with dementia of the degenerate type. Brain Res 717:154–159
Zurück zum Zitat Urata Y, Honma S, Goto S, Todoroki S, Iida T, Cho S, Honma K, Kondo T (1999) Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells. Free Radic Biol Med 27:838–847 Urata Y, Honma S, Goto S, Todoroki S, Iida T, Cho S, Honma K, Kondo T (1999) Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells. Free Radic Biol Med 27:838–847
Zurück zum Zitat van Someren EJ (2000) Circadian and sleep disturbances in the elderly. Exp Gerontol 35:1229–1237 van Someren EJ (2000) Circadian and sleep disturbances in the elderly. Exp Gerontol 35:1229–1237
Zurück zum Zitat Vekrellis K, Xilouri M, Emmanouilidou E, Rideout HJ, Stefanis L (2011) Pathological roles of alpha-synuclein in neurological disorders. Lancet Neurol 10:1015–1025 Vekrellis K, Xilouri M, Emmanouilidou E, Rideout HJ, Stefanis L (2011) Pathological roles of alpha-synuclein in neurological disorders. Lancet Neurol 10:1015–1025
Zurück zum Zitat Venegas C, García JA, Escames G, Ortiz F, Lopez A, Doerrier C, García-Corzo L, Lopez LC, Reiter RJ, Acuña-Castroviejo D (2012) Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J Pineal Res 52:217–227 Venegas C, García JA, Escames G, Ortiz F, Lopez A, Doerrier C, García-Corzo L, Lopez LC, Reiter RJ, Acuña-Castroviejo D (2012) Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J Pineal Res 52:217–227
Zurück zum Zitat Voordouw BC, Euser R, Verdonk RE, Alberda BT, de Jong FH, Drogendijk AC, Fauser BC, Cohen M (1992) Melatonin and melatonin–progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab 74:108–117 Voordouw BC, Euser R, Verdonk RE, Alberda BT, de Jong FH, Drogendijk AC, Fauser BC, Cohen M (1992) Melatonin and melatonin–progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab 74:108–117
Zurück zum Zitat Wada K, Chatzipanteli K, Busto R, Dietrich WD (1998) Role of nitric oxide in traumatic brain injury in the rat. J Neurosurg 89:807–818 Wada K, Chatzipanteli K, Busto R, Dietrich WD (1998) Role of nitric oxide in traumatic brain injury in the rat. J Neurosurg 89:807–818
Zurück zum Zitat Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, Zisapel N (2007) Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin 23:2597–2605 Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, Zisapel N (2007) Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin 23:2597–2605
Zurück zum Zitat Waldhauser F, Steger H (1986) Changes in melatonin secretion with age and pubescence. J Neural Transm Suppl 21:183–197 Waldhauser F, Steger H (1986) Changes in melatonin secretion with age and pubescence. J Neural Transm Suppl 21:183–197
Zurück zum Zitat Waldhauser F, Waldhauser M, Lieberman HR, Deng MH, Lynch HJ, Wurtman RJ (1984) Bioavailability of oral melatonin in humans. Neuroendocrinology 39:307–313 Waldhauser F, Waldhauser M, Lieberman HR, Deng MH, Lynch HJ, Wurtman RJ (1984) Bioavailability of oral melatonin in humans. Neuroendocrinology 39:307–313
Zurück zum Zitat Wang X (2009) The antiapoptotic activity of melatonin in neurodegenerative diseases. CNS Neurosci Ther 15:345–357 Wang X (2009) The antiapoptotic activity of melatonin in neurodegenerative diseases. CNS Neurosci Ther 15:345–357
Zurück zum Zitat Wang X, Sirianni A, Pei Z, Cormier K, Smith K, Jiang J, Zhou S, Wang H, Zhao R, Yano H, Kim JE, Li W, Kristal BS, Ferrante RJ, Friedlander RM (2011) The melatonin MT1 receptor axis modulates mutant Huntingtin-mediated toxicity. J Neurosci 31:14496–14507 Wang X, Sirianni A, Pei Z, Cormier K, Smith K, Jiang J, Zhou S, Wang H, Zhao R, Yano H, Kim JE, Li W, Kristal BS, Ferrante RJ, Friedlander RM (2011) The melatonin MT1 receptor axis modulates mutant Huntingtin-mediated toxicity. J Neurosci 31:14496–14507
Zurück zum Zitat Weishaupt JH, Bartels C, Polking E, Dietrich J, Rohde G, Poeggeler B, Mertens N, Sperling S, Bohn M, Huther G, Schneider A, Bach A, Siren AL, Hardeland R, Bahr M, Nave KA, Ehrenreich H (2006) Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res 41:313–323 Weishaupt JH, Bartels C, Polking E, Dietrich J, Rohde G, Poeggeler B, Mertens N, Sperling S, Bohn M, Huther G, Schneider A, Bach A, Siren AL, Hardeland R, Bahr M, Nave KA, Ehrenreich H (2006) Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res 41:313–323
Zurück zum Zitat Wiesenberg I, Missbach M, Kahlen JP, Schrader M, Carlberg C (1995) Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand. Nucleic Acids Res 23:327–333 Wiesenberg I, Missbach M, Kahlen JP, Schrader M, Carlberg C (1995) Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand. Nucleic Acids Res 23:327–333
Zurück zum Zitat Willis GL (2008) Parkinson’s disease as a neuroendocrine disorder of circadian function: dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process. Rev Neurosci 19:245–316 Willis GL (2008) Parkinson’s disease as a neuroendocrine disorder of circadian function: dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process. Rev Neurosci 19:245–316
Zurück zum Zitat Willis GL, Armstrong SM (1999) A therapeutic role for melatonin antagonism in experimental models of Parkinson’s disease. Physiol Behav 66:785–795 Willis GL, Armstrong SM (1999) A therapeutic role for melatonin antagonism in experimental models of Parkinson’s disease. Physiol Behav 66:785–795
Zurück zum Zitat Willis GL, Robertson AD (2004) Recovery of experimental Parkinson’s disease with the melatonin analogues ML-23 and S-20928 in a chronic, bilateral 6-OHDA model: a new mechanism involving antagonism of the melatonin receptor. Pharmacol Biochem Behav 79:413–429 Willis GL, Robertson AD (2004) Recovery of experimental Parkinson’s disease with the melatonin analogues ML-23 and S-20928 in a chronic, bilateral 6-OHDA model: a new mechanism involving antagonism of the melatonin receptor. Pharmacol Biochem Behav 79:413–429
Zurück zum Zitat Willis GL, Turner EJ (2007) Primary and secondary features of Parkinson’s disease improve with strategic exposure to bright light: a case series study. Chronobiol Int 24:521–537 Willis GL, Turner EJ (2007) Primary and secondary features of Parkinson’s disease improve with strategic exposure to bright light: a case series study. Chronobiol Int 24:521–537
Zurück zum Zitat Wilson SJ, Nutt DJ, Alford C, Argyropoulos SV, Baldwin DS, Bateson AN, Britton TC, Crowe C, Dijk DJ, Espie CA, Gringras P, Hajak G, Idzikowski C, Krystal AD, Nash JR, Selsick H, Sharpley AL, Wade AG (2010) British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol 24:1577–1601 Wilson SJ, Nutt DJ, Alford C, Argyropoulos SV, Baldwin DS, Bateson AN, Britton TC, Crowe C, Dijk DJ, Espie CA, Gringras P, Hajak G, Idzikowski C, Krystal AD, Nash JR, Selsick H, Sharpley AL, Wade AG (2010) British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol 24:1577–1601
Zurück zum Zitat Wu YH, Swaab DF (2007) Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer’s disease. Sleep Med 8:623–636 Wu YH, Swaab DF (2007) Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer’s disease. Sleep Med 8:623–636
Zurück zum Zitat Wu YH, Feenstra MG, Zhou JN, Liu RY, Torano JS, Van Kan HJ, Fischer DF, Ravid R, Swaab DF (2003) Molecular changes underlying reduced pineal melatonin levels in Alzheimer disease: alterations in preclinical and clinical stages. J Clin Endocrinol Metab 88:5898–5906 Wu YH, Feenstra MG, Zhou JN, Liu RY, Torano JS, Van Kan HJ, Fischer DF, Ravid R, Swaab DF (2003) Molecular changes underlying reduced pineal melatonin levels in Alzheimer disease: alterations in preclinical and clinical stages. J Clin Endocrinol Metab 88:5898–5906
Zurück zum Zitat Wu J, Seregard S, Algvere PV (2006a) Photochemical damage of the retina. Surv Ophthalmol 51:461–481 Wu J, Seregard S, Algvere PV (2006a) Photochemical damage of the retina. Surv Ophthalmol 51:461–481
Zurück zum Zitat Wu YH, Zhou JN, Balesar R, Unmehopa U, Bao A, Jockers R, Van Heerikhuize J, Swaab DF (2006b) Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone. J Comp Neurol 499:897–910 Wu YH, Zhou JN, Balesar R, Unmehopa U, Bao A, Jockers R, Van Heerikhuize J, Swaab DF (2006b) Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone. J Comp Neurol 499:897–910
Zurück zum Zitat Wu YH, Zhou JN, Van Heerikhuize J, Jockers R, Swaab DF (2007) Decreased MT1 melatonin receptor expression in the suprachiasmatic nucleus in aging and Alzheimer’s disease. Neurobiol Aging 28:1239–1247 Wu YH, Zhou JN, Van Heerikhuize J, Jockers R, Swaab DF (2007) Decreased MT1 melatonin receptor expression in the suprachiasmatic nucleus in aging and Alzheimer’s disease. Neurobiol Aging 28:1239–1247
Zurück zum Zitat Wurtman RJ, Zhdanova I (1995) Improvement of sleep quality by melatonin. Lancet 346:1491 Wurtman RJ, Zhdanova I (1995) Improvement of sleep quality by melatonin. Lancet 346:1491
Zurück zum Zitat Yang X, Yang Y, Fu Z, Li Y, Feng J, Luo J, Zhang Q, Wang Q, Tian Q (2011) Melatonin ameliorates Alzheimer-like pathological changes and spatial memory retention impairment induced by calyculin A. J Psychopharmacol 25:1118–1125 Yang X, Yang Y, Fu Z, Li Y, Feng J, Luo J, Zhang Q, Wang Q, Tian Q (2011) Melatonin ameliorates Alzheimer-like pathological changes and spatial memory retention impairment induced by calyculin A. J Psychopharmacol 25:1118–1125
Zurück zum Zitat Yuan H, Pang SF (1991) [125I]Iodomelatonin-binding sites in the pigeon brain: binding characteristics, regional distribution and diurnal variation. J Endocrinol 128:475–482 Yuan H, Pang SF (1991) [125I]Iodomelatonin-binding sites in the pigeon brain: binding characteristics, regional distribution and diurnal variation. J Endocrinol 128:475–482
Zurück zum Zitat Zeitzer JM, Daniels JE, Duffy JF, Klerman EB, Shanahan TL, Dijk DJ, Czeisler CA (1999) Do plasma melatonin concentrations decline with age? Am J Med 107:432–436 Zeitzer JM, Daniels JE, Duffy JF, Klerman EB, Shanahan TL, Dijk DJ, Czeisler CA (1999) Do plasma melatonin concentrations decline with age? Am J Med 107:432–436
Zurück zum Zitat Zhang Y, Dawson VL, Dawson TM (2000) Oxidative stress and genetics in the pathogenesis of Parkinson’s disease. Neurobiol Dis 7:240–250 Zhang Y, Dawson VL, Dawson TM (2000) Oxidative stress and genetics in the pathogenesis of Parkinson’s disease. Neurobiol Dis 7:240–250
Zurück zum Zitat Zhang Q, Ding H, Li W, Fan Z, Sun A, Luo J, Ke ZJ (2009) Senescence accelerated mouse strain is sensitive to neurodegeneration induced by mild impairment of oxidative metabolism. Brain Res 1264:111–118 Zhang Q, Ding H, Li W, Fan Z, Sun A, Luo J, Ke ZJ (2009) Senescence accelerated mouse strain is sensitive to neurodegeneration induced by mild impairment of oxidative metabolism. Brain Res 1264:111–118
Zurück zum Zitat Zhong G, Naismith SL, Rogers NL, Lewis SJ (2011) Sleep-wake disturbances in common neurodegenerative diseases: a closer look at selected aspects of the neural circuitry. J Neurol Sci 307:9–14 Zhong G, Naismith SL, Rogers NL, Lewis SJ (2011) Sleep-wake disturbances in common neurodegenerative diseases: a closer look at selected aspects of the neural circuitry. J Neurol Sci 307:9–14
Zurück zum Zitat Zhou JN, Liu RY, Kamphorst W, Hofman MA, Swaab DF (2003) Early neuropathological Alzheimer’s changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels. J Pineal Res 35:125–130 Zhou JN, Liu RY, Kamphorst W, Hofman MA, Swaab DF (2003) Early neuropathological Alzheimer’s changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels. J Pineal Res 35:125–130
Metadaten
Titel
Melatonin Antioxidative Defense: Therapeutical Implications for Aging and Neurodegenerative Processes
verfasst von
Seithikurippu R. Pandi-Perumal
Ahmed S. BaHammam
Gregory M. Brown
D. Warren Spence
Vijay K. Bharti
Charanjit Kaur
Rüdiger Hardeland
Daniel P. Cardinali
Publikationsdatum
01.04.2013
Verlag
Springer-Verlag
Erschienen in
Neurotoxicity Research / Ausgabe 3/2013
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI
https://doi.org/10.1007/s12640-012-9337-4

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