nach oben

Metabolic Brain Disease

Erschienen in:

17.04.2018 | Original Article

5-Hydroxytryptamine receptor 6 antagonist, SB258585 exerts neuroprotection in a rat model of Streptozotocin-induced Alzheimer’s disease

verfasst von: Nasrin Hashemi-Firouzi, Siamak Shahidi, Sara Soleimani-Asl, Alireza Komaki

Erschienen in: Metabolic Brain Disease | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory decline. It has been suggested that 5-hydroxytryptamine receptor 6 (5-HT6R) might be involved in AD pathology. The aim of this study was to evaluate the effect of a 5-HT6R antagonist on cognition, learning, memory, and hippocampal apoptosis in an experimental rat model of AD. AD was induced by intracerebroventricular (icv) administration of streptozotocin (STZ; 3 mg/kg, 10 μL, twice). Adult, male rats were divided into the following groups: control, sham, AD (saline treatment, 1 μL icv for 30 days), and AD + SB258585 (5-HT6R antagonist, 1 μg/μL icv for 30 days). Following the treatment period, novel object recognition (NOR) and passive avoidance learning (PAL) tests were conducted to measure cognition, as well as learning and memory, respectively. TUNEL staining was used to evaluate apoptosis in the hippocampus. This study demonstrates that icv STZ injections induce apoptosis in hippocampal cells, decrease the NOR discrimination index, increase the number of trials needed to reach acquisition and the time spent in the dark compartment during PAL, as compared with sham and control groups. Subsequent administration of SB258585 in the STZ treated rats increased the NOR discrimination index, decreased the number of trials till acquisition and the time spent in the dark compartment during PAL, while decreasing neuronal apoptosis, as compared to the untreated AD group. Thus, we conclude that long-term administration of the 5-HT6R antagonist SB258585, ameliorates AD-associated cognitive and behavioral impairments through the suppression of apoptosis in the hippocampus.

Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process 13:93–110CrossRefPubMed

Asl SS, Mousavizedeh K, Pourheydar B, Soleimani M, Rahbar E, Mehdizadeh M (2013) Protective effects of N-acetylcysteine on 3, 4-methylenedioxymethamphetamine-induced neurotoxicity in male Sprague–Dawley rats. Metab Brain Dis 28:677–686CrossRef

Atukeren P, Cengiz M, Yavuzer H, Gelisgen R, Altunoglu E, Oner S, Erdenen F, Yuceakın D, Derici H, Cakatay U, Uzun H (2017) The efficacy of donepezil administration on acetylcholinesterase activity and altered redox homeostasis in Alzheimer’s disease. Biomed Pharmacother 90:786–795CrossRefPubMed

Azad N, Rasoolijazi H, Joghataie MT, Soleimani S (2011) Neuroprotective effects of carnosic acid in an experimental model of Alzheimer's disease in rats. Cell J 13:39–44PubMedPubMedCentral

Barilar JO, Knezovic A, Grünblatt E, Riederer P, Salkovic-Petrisic M (2015) Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer’s disease. J Neural Transm 122:565–576CrossRefPubMed

Barker GR, Bird F, Alexander V, Warburton EC (2007) Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex. J Neurosci 27:2948–2957CrossRefPubMed

Barzegar S, Komaki A, Shahidi S, Sarihi A, Mirazi N, Salehi I (2015) Effects of cannabinoid and glutamate receptor antagonists and their interactions on learning and memory in male rats. Pharmacol Biochem Behav 131:87–90. https://doi.org/10.1016/j.pbb.2015.02.005 CrossRefPubMed

Benhamu B, Martin-Fontecha M, Vazquez-Villa H, Pardo L, Lopez-Rodriguez ML (2014) Serotonin 5-HT6 receptor antagonists for the treatment of cognitive deficiency in Alzheimer's disease. J Med Chem 57:7160–7181. https://doi.org/10.1021/jm5003952 CrossRefPubMed

Bignami G (1965) Selection for high rates and low rates of avoidance conditioning in the rat. Anim Behav 13:221–227CrossRefPubMed

Borsini F, Bordi F, Riccioni T (2011) 5-HT6 pharmacology inconsistencies. Pharmacol Biochem Behav 98:169–172. https://doi.org/10.1016/j.pbb.2010.12.021 CrossRefPubMed

Bromidge SM, Brown AM, Clarke SE, Dodgson K, Gager T, Grassam HL, Jeffrey PM, Joiner GF, King FD, Middlemiss DN, Moss SF, Newman H, Riley G, Routledge C, Wyman P (1999) 5-Chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfon-amide (SB-271046): a potent, selective, and orally bioavailable 5-HT6 receptor antagonist. J Med Chem 42:202–205CrossRefPubMed

Chen S, A-r L, An F-m, W-b Y, X-d G (2012) Amelioration of neurodegenerative changes in cellular and rat models of diabetes-related Alzheimer’s disease by exendin-4. Age 34:1211–1224CrossRefPubMed

Cheng XL, Li MK (2014) Effect of topiramate on apoptosis-related protein expression of hippocampus in model rats with Alzheimers disease. Eur Rev For Med and Pharmacol Sci 18:761–768

Claeysen S, Jl B, Giannoni P (2015) Serotonin: a new hope in Alzheimer’s disease? Publications, ACS

Da Silva Costa-Aze V, Quiedeville A, Boulouard M, Dauphin F (2012) 5-HT6 receptor blockade differentially affects scopolamine-induced deficits of working memory, recognition memory and aversive learning in mice. Psychopharmacology 222:99–115. https://doi.org/10.1007/s00213-011-2627-3 CrossRefPubMed

Dawson LA, Nguyen HQ, Li P (2001) The 5-HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 25:662–668. https://doi.org/10.1016/s0893-133x(01)00265-2 CrossRefPubMed

de Bruin NM et al (2011) Two novel 5-HT6 receptor antagonists ameliorate scopolamine-induced memory deficits in the object recognition and object location tasks in Wistar rats. Neurobiol Learn Mem 96:392–402. https://doi.org/10.1016/j.nlm.2011.06.015 CrossRefPubMed

Dehkordi NG, Noorbakhshnia M, Ghaedi K, Esmaeili A, Dabaghi M (2015) Omega-3 fatty acids prevent LPS-induced passive avoidance learning and memory and CaMKII-alpha gene expression impairments in hippocampus of rat Pharmacological reports. Pharmacol Rep 67:370–375. https://doi.org/10.1016/j.pharep.2014.10.014 CrossRefPubMed

Duhr F, Déléris P, Raynaud F, Séveno M, Morisset-Lopez S, Mannoury la Cour C, Millan MJ, Bockaert J, Marin P, Chaumont-Dubel S (2014) Cdk5 induces constitutive activation of 5-HT6 receptors to promote neurite growth. Nat Chem Biol 10:590–597. https://doi.org/10.1038/nchembio.1547 CrossRefPubMed

Ennaceur A, Delacour J (1988) A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res 31:47–59CrossRefPubMed

Erdoğan ME, Aydın S, Yanar K, Mengi M, Kansu AD, Cebe T, Belce A, Çelikten M, Cakatay U (2017) The effects of lipoic acid on redox status in brain regions and systemic circulation in streptozotocin-induced sporadic Alzheimer’s disease model. Metab Brain Dis 32(4):1017–1031

Filip M, Bader M (2009) Overview on 5-HT receptors and their role in physiology and pathology of the central nervous system. Pharmacol Rep 61:761–777CrossRefPubMed

Foley AG, Murphy KJ, Hirst WD, Gallagher HC, Hagan JJ, Upton N, Walsh FS, Regan CM (2004) The 5-HT(6) receptor antagonist SB-271046 reverses scopolamine-disrupted consolidation of a passive avoidance task and ameliorates spatial task deficits in aged rats. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 29:93–100. https://doi.org/10.1038/sj.npp.1300332 CrossRefPubMed

Foley AG et al (2008) The selective 5-HT6 receptor antagonists SB-271046 and SB-399885 potentiate NCAM PSA immunolabeling of dentate granule cells, but not neurogenesis, in the hippocampal formation of mature Wistar rats. Neuropharmacology 54:1166–1174. https://doi.org/10.1016/j.neuropharm.2008.03.012 CrossRefPubMed

Ghahremanitamadon F, Shahidi S, Zargooshnia S, Nikkhah A, Ranjbar A, Soleimani Asl S (2014) Protective effects of Borago officinalis extract on amyloid beta-peptide(25-35)-induced memory impairment in male rats: a behavioral study. Biomed Res Int 2014:798535. https://doi.org/10.1155/2014/798535 CrossRefPubMedPubMedCentral

Gothert M (2013) Serotonin discovery and stepwise disclosure of 5-HT receptor complexity over four decades. Part I. General background and discovery of serotonin as a basis for 5-HT receptor identification. Pharmacol Rep 65:771–786CrossRefPubMed

Gravius A, Laszy J, Pietraszek M, Sághy K, Nagel J, Chambon C, Wegener N, Valastro B, Danysz W, Gyertyán I (2011) Effects of 5-HT6 antagonists, Ro-4368554 and SB-258585, in tests used for the detection of cognitive enhancement and antipsychotic-like activity. Behav Pharmacol 22:122–135. https://doi.org/10.1097/FBP.0b013e328343d804 CrossRefPubMed

Green RC, Cupples LA, Kurz A, Auerbach S, Go R, Sadovnick D, Duara R, Kukull WA, Chui H, Edeki T, Griffith PA, Friedland RP, Bachman D, Farrer L (2003) Depression as a risk factor for Alzheimer disease: the MIRAGE study. Arch Neurol 60:753–759CrossRefPubMed

Grieb P (2016) Intracerebroventricular Streptozotocin injections as a model of Alzheimer's disease: in search of a relevant mechanism. Mol Neurobiol 53:1741–1752. https://doi.org/10.1007/s12035-015-9132-3 CrossRefPubMed

Hasanein P, Shahidi S (2012) Preventive effect of Teucrium polium on learning and memory deficits in diabetic rats Medical science monitor : international medical journal of experimental and clinical research 18:Br41–46

Hashemi-Firouzi N, Akhavan M, Komaki A, Shahidi S (2015) Effects of acute Administration of Urtica dioica on the novel object-recognition task in mice Avicenna Journal of Neuro Psych Physiology 2

Hashemi-Firouzi N, Komaki A, Soleimani Asl S, Shahidi S (2017) The effects of the 5-HT7 receptor on hippocampal long-term potentiation and apoptosis in a rat model of Alzheimer's disease. Brain Res Bull 135:85–91. https://doi.org/10.1016/j.brainresbull.2017.10.004 CrossRefPubMed

Hirano K, Piers TM, Searle KL, Miller ND, Rutter AR, Chapman PF (2009) Procognitive 5-HT6 antagonists in the rat forced swimming test: potential therapeutic utility in mood disorders associated with Alzheimer's disease. Life Sci 84:558–562. https://doi.org/10.1016/j.lfs.2009.01.019 CrossRefPubMed

Hirst WD, Stean TO, Rogers DC, Sunter D, Pugh P, Moss SF, Bromidge SM, Riley G, Smith DR, Bartlett S, Heidbreder CA, Atkins AR, Lacroix LP, Dawson LA, Foley AG, Regan CM, Upton N (2006) SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models. Eur J Pharmacol 553:109–119. https://doi.org/10.1016/j.ejphar.2006.09.049 CrossRefPubMed

Ivachtchenko AV, Ivanenkov YA, Veselov MS, Okun IM (2017) AVN-322 is a safe orally bio-available potent and highly selective antagonist of 5-HT6R with demonstrated ability to improve impaired memory in animal models. Curr Alzheimer Res 14:268–294. https://doi.org/10.2174/1567205013666161108105005 PubMedCrossRef

Jabbarpour Z, Shahidi S, Saidijam M, Sarihi A, Hassanzadeh T, Esmaeili R (2014) Effect of tempol on the passive avoidance and novel object recognition task in diabetic rats. Brain Res Bull 101:51–56. https://doi.org/10.1016/j.brainresbull.2013.12.013 CrossRefPubMed

Khalili M, Roghani M, Ekhlasi M (2010) The effect of aqueous crocus sativus L. extract on intracerebroventricular streptozotocin-induced cognitive deficits in rat: a behavioral analysis. Iranian Journal of Pharmaceutical Research:185–191

Khodamoradi N, Komaki A, Salehi I, Shahidi S, Sarihi A (2015) Effect of vitamin E on lead exposure-induced learning and memory impairment in rats. Physiol Behav 144:90–94. https://doi.org/10.1016/j.physbeh.2015.03.015 CrossRefPubMed

King MV, Sleight AJ, Woolley ML, Topham IA, Marsden CA, Fone KC (2004) 5-HT6 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation--an effect sensitive to NMDA receptor antagonism. Neuropharmacology 47:195–204. https://doi.org/10.1016/j.neuropharm.2004.03.012 CrossRefPubMed

King MV, Spicer CH, Sleight AJ, Marsden CA, Fone KC (2009) Impact of regional 5-HT depletion on the cognitive enhancing effects of a typical 5-ht(6) receptor antagonist, Ro 04-6790, in the novel object discrimination task. Psychopharmacology 202:111–123. https://doi.org/10.1007/s00213-008-1334-1 CrossRefPubMed

Komaki A, Karimi SA, Salehi I, Sarihi A, Shahidi S, Zarei M (2015) The treatment combination of vitamins E and C and astaxanthin prevents high-fat diet induced memory deficits in rats. Pharmacol Biochem Behav 131:98–103. https://doi.org/10.1016/j.pbb.2015.02.008 CrossRefPubMed

Lin F, Jia J, Qin W (2014) Enhancement of β-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, which involves central insulin signaling in a transgenic mouse model. Neuroreport 25:1289–1295CrossRefPubMed

Liu K-C, Li JY, Tan HH, du CX, Xie W, Zhang YM, Ma WL, Zhang L (2015) Serotonin 6 receptors in the dorsal hippocampus regulate depressive-like behaviors in unilateral 6-hydroxydopamine-lesioned Parkinson's rats. Neuropharmacology 95:290–298CrossRefPubMed

Mahmoodi M, Shahidi S, Hasanein P (2011) Involvement of the ventral tegmental area in the inhibitory avoidance memory in rats. Physiol Behav 102:542–547. https://doi.org/10.1016/j.physbeh.2011.01.011 CrossRefPubMed

Marcos B, Gil-Bea FJ, Hirst WD, Garcia-Alloza M, Ramirez MJ (2006) Lack of localization of 5-HT6 receptors on cholinergic neurons: implication of multiple neurotransmitter systems in 5-HT6 receptor-mediated acetylcholine release. Eur J Neurosci 24:1299–1306. https://doi.org/10.1111/j.1460-9568.2006.05003.x CrossRefPubMed

Marcos B, Chuang TT, Gil-Bea FJ, Ramirez MJ (2008) Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of cognitive impairment in the rat. Br J Pharmacol 155:434–440. https://doi.org/10.1038/bjp.2008.281 CrossRefPubMedPubMedCentral

Marcos B, Cabero M, Solas M, Aisa B, Ramirez MJ (2010) Signalling pathways associated with 5-HT6 receptors: relevance for cognitive effects. Int J Neuropsychopharmacol 13:775–784CrossRefPubMed

Mitchell ES, Sexton T, Neumaier JF (2007) Increased expression of 5-HT6 receptors in the rat dorsomedial striatum impairs instrumental learning. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 32:1520–1530CrossRefPubMed

Mørk A, Russell RV, de Jong IE, Smagin G (2017) Effects of the 5-HT 6 receptor antagonist idalopirdine on extracellular levels of monoamines, glutamate and acetylcholine in the rat medial prefrontal cortex. Eur J Pharmacol 799:1–6CrossRefPubMed

Nazem A, Sankowski R, Bacher M, Al-Abed Y (2015) Rodent models of neuroinflammation for Alzheimer's disease. J Neuroinflammation 12:74. https://doi.org/10.1186/s12974-015-0291-y CrossRefPubMedPubMedCentral

Nygaard HB, van Dyck CH, Strittmatter SM (2014) Fyn kinase inhibition as a novel therapy for Alzheimer’s disease. Alzheimers Res Ther 6:8CrossRefPubMedPubMedCentral

Obulesu M, Lakshmi MJ (2014) Apoptosis in Alzheimer's disease: an understanding of the physiology, pathology and therapeutic avenues. Neurochem Res 39:2301–2312. https://doi.org/10.1007/s11064-014-1454-4 CrossRefPubMed

Ögren SO, Stiedl O (2015) Passive avoidance. In: Encyclopedia of psychopharmacology. Springer, pp 1220–1228

Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D (2006) Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry 63:530–538CrossRefPubMedPubMedCentral

Paxinos GW C. 2007 The rat brain in stereotaxic coordinates Burlington MA Elsevier Inc

Pineda-Farias JB, Barragán-Iglesias P, Valdivieso-Sánchez A, Rodríguez-Silverio J, Flores-Murrieta FJ, Granados-Soto V, Rocha-González HI (2017) Spinal 5-HT 4 and 5-HT 6 receptors contribute to the maintenance of neuropathic pain in rats Pharmacological Reports

Plaschke K, Kopitz J, Siegelin M, Schliebs R, Salkovic-Petrisic M, Riederer P, Hoyer S (2010) Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AβPP-overexpressing mice. J Alzheimers Dis 19:691–704CrossRefPubMed

Pourheydar B, Soleimani Asl S, Azimzadeh M, Rezaei Moghadam A, Marzban A, Mehdizadeh M (2016) Neuroprotective effects of bone marrow mesenchymal stem cells on bilateral common carotid arteries occlusion model of cerebral ischemia in rat. Behav Neurol 2016:2964712. https://doi.org/10.1155/2016/2964712

Quiedeville A, Boulouard M, Hamidouche K, da Silva Costa-Aze V, Nee G, Rochais C, Dallemagne P, Fabis F, Freret T, Bouet V (2015) Chronic activation of 5-HT4 receptors or blockade of 5-HT6 receptors improve memory performances. Behav Brain Res 293:10–17. https://doi.org/10.1016/j.bbr.2015.07.020 CrossRefPubMed

Radi E, Formichi P, Battisti C, Federico A (2014) Apoptosis and oxidative stress in neurodegenerative diseases. J of Alzheimer's Dis 42(Suppl 3):S125–S152. https://doi.org/10.3233/jad-132738 CrossRef

Ramirez MJ, Lai MK, Tordera RM, Francis PT (2014) Serotonergic therapies for cognitive symptoms in Alzheimer's disease: rationale and current status. Drugs 74:729–736. https://doi.org/10.1007/s40265-014-0217-5 CrossRefPubMed

Ravelli KG, dos Anjos Rosário B, Camarini R, Hernandes MS, Britto LR (2017) Intracerebroventricular Streptozotocin as a model of Alzheimer’s disease: neurochemical and behavioral characterization in mice. Neurotox Res 31:327–333CrossRefPubMed

Rescorla RA, Solomon RL (1967) Two-process learning theory: relationships between Pavlovian conditioning and instrumental learning. Psychol Rev 74:151–182CrossRefPubMed

Rogers DC, Hagan JJ (2001) 5-HT6 receptor antagonists enhance retention of a water maze task in the rat. Psychopharmacology 158:114–119. https://doi.org/10.1007/s002130100840 CrossRefPubMed

Salkovic-Petrisic M, Osmanovic-Barilar J, Bruckner MK, Hoyer S, Arendt T, Riederer P (2011) Cerebral amyloid angiopathy in streptozotocin rat model of sporadic Alzheimer's disease: a long-term follow up study. J of Neural Transm (Vienna, Austria : 1996) 118:765–772. https://doi.org/10.1007/s00702-011-0651-4 CrossRef

Salkovic-Petrisic M, Knezovic A, Hoyer S, Riederer P (2013) What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer's disease, about the therapeutic strategies in Alzheimer's research. J of Neural Transm (Vienna, Austria : 1996) 120:233–252. https://doi.org/10.1007/s00702-012-0877-9 CrossRef

Schaffhauser H, Mathiasen JR, DiCamillo A, Huffman MJ, Lu LD, McKenna BA, Qian J, Marino MJ (2009) Dimebolin is a 5-HT6 antagonist with acute cognition enhancing activities. Biochem Pharmacol 78:1035–1042. https://doi.org/10.1016/j.bcp.2009.06.021 CrossRefPubMed

Shahidi S, Setareye S, Mahmoodi M (2013) Effect of Prunus domestica L. (mirabelle) on learning and memory in mice. Anc Sci Life 32:139–143. https://doi.org/10.4103/0257-7941.122996 CrossRefPubMedPubMedCentral

Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW, Pinkert CA, Amin R, Dhanasekaran M, Suppiramaniam V (2012) Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents Neurobiol of Aging 33:430.e435–e418 https://doi.org/10.1016/j.neurobiolaging.2010.12.002

Silva AJ, Kogan JH, Frankland PW, Kida S (1998) CREB and memory. Annu Rev Neurosci 21:127–148. https://doi.org/10.1146/annurev.neuro.21.1.127 CrossRefPubMed

Takuma K, Hara Y, Kataoka S, Kawanai T, Maeda Y, Watanabe R, Takano E, Hayata-Takano A, Hashimoto H, Ago Y, Matsuda T (2014) Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism. Pharmacol Biochem Behav 126:43–49. https://doi.org/10.1016/j.pbb.2014.08.013 CrossRefPubMed

Terwel D, Prickaerts J, Meng F, Jolles J (1995) Brain enzyme activities after intracerebroventricular injection of streptozotocin in rats receiving acetyl-L-carnitine. Eur J Pharmacol 287:65–71CrossRefPubMed

Veisi M, Shahidi S, Komaki A, Sarihi A (2014) Effect of lemon Verbena on memory of male rats. Avicenna Journal of Neuro Psych Physiology 1

Wang CC, Man GCW, Chu CY, Borchert A, Ugun-Klusek A, Billett EE, Kühn H, Ufer C (2014) Serotonin receptor 6 mediates defective brain development in monoamine oxidase A-deficient mouse embryos. The J of Biol Chem 289:8252–8263. https://doi.org/10.1074/jbc.M113.522094 CrossRef

Wesołowska A, Nikiforuk A, Stachowicz K, Tatarczyńska E (2006) Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression. Neuropharmacology 51:578–586. https://doi.org/10.1016/j.neuropharm.2006.04.017 CrossRefPubMed

Wesolowska A, Nikiforuk A, Stachowicz K (2007) Anxiolytic-like and antidepressant-like effects produced by the selective 5-HT6 receptor antagonist SB-258585 after intrahippocampal administration to rats. Behav Pharmacol 18:439–446. https://doi.org/10.1097/FBP.0b013e3282d28f9c CrossRefPubMed

West P, Marcy V, Marino M, Schaffhauser H (2009) Activation of the 5-HT 6 receptor attenuates long-term potentiation and facilitates GABAergic neurotransmission in rat hippocampus. Neuroscience 164:692–701CrossRefPubMed

Wilkinson D, Windfeld K, Colding-Jorgensen E (2014) Safety and efficacy of idalopirdine, a 5-HT6 receptor antagonist, in patients with moderate Alzheimer's disease (LADDER): a randomised, double-blind, placebo-controlled phase 2 trial. The Lancet Neurol 13:1092–1099. https://doi.org/10.1016/s1474-4422(14)70198-x CrossRefPubMed

Woods S, Clarke NN, Layfield R, Fone KC (2012) 5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms. Br J Pharmacol 167:436–449. https://doi.org/10.1111/j.1476-5381.2012.02022.x CrossRefPubMedPubMedCentral

Yun HM, Rhim H (2011) The serotonin-6 receptor as a novel therapeutic target. Exp Neurobiol 20:159–168. https://doi.org/10.5607/en.2011.20.4.159 CrossRefPubMedPubMedCentral

Yun H-M, Kim S, Kim HJ, Kostenis E, Kim JI, Seong JY, Baik JH, Rhim H (2007) The novel cellular mechanism of human 5-HT6 receptor through an interaction with Fyn. J Biol Chem 282:5496–5505CrossRefPubMed

Yun HM, Park KR, Kim EC, Kim S, Hong JT (2015) Serotonin 6 receptor controls alzheimer’s disease and depression. Oncotarget 6(29):26716–28. https://doi.org/10.18632/oncotarget.5777

Titel: 5-Hydroxytryptamine receptor 6 antagonist, SB258585 exerts neuroprotection in a rat model of Streptozotocin-induced Alzheimer’s disease
verfasst von: Nasrin Hashemi-Firouzi
Siamak Shahidi
Sara Soleimani-Asl
Alireza Komaki
Publikationsdatum: 17.04.2018
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 4/2018
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-018-0228-0

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

23.04.2024 | Demenz | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

5-Hydroxytryptamine receptor 6 antagonist, SB258585 exerts neuroprotection in a rat model of Streptozotocin-induced Alzheimer’s disease

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2018

Cortical and subcortical gray matter structural alterations in normoglycemic obese and type 2 diabetes patients: relationship with adiposity, glucose, and insulin

Cytoplasmic FMRP interacting protein 1/2 (CYFIP1/2) expression analysis in autism

Four Gaucher disease type II patients with three novel mutations: a single centre experience from Turkey

Neuroprotective efficiency of Mangifera indica leaves extract on cadmium-induced cortical damage in rats

Increased adiponectin is associated with cerebral white matter lesions in the elderly with cognitive impairment

Cerebellar atrophy is common among mitochondrial disorders

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie