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Methylphenidate Decreases ATP Levels and Impairs Glutamate Uptake and Na+,K+-ATPase Activity in Juvenile Rat Hippocampus

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Abstract

The study of the long-term neurological consequences of early exposure with methylphenidate (MPH) is very important since this psychostimulant has been widely misused by children and adolescents who do not meet full diagnostic criteria for ADHD. The aim of this study was to examine the effect of early chronic exposure with MPH on amino acids profile, glutamatergic and Na+,K+-ATPase homeostasis, as well as redox and energy status in the hippocampus of juvenile rats. Wistar male rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 45th day of age. Results showed that MPH altered amino acid profile in the hippocampus, decreasing glutamine levels. Glutamate uptake and Na+,K+-ATPase activity were decreased after chronic MPH exposure in the hippocampus of rats. No changes were observed in the immunocontents of glutamate transporters (GLAST and GLT-1), and catalytic subunits of Na+,K+-ATPase (α1, α2, and α3), as well as redox status. Moreover, MPH provoked a decrease in ATP levels in the hippocampus of chronically exposed rats, while citrate synthase, succinate dehydrogenase, respiratory chain complexes activities (II, II–III, and IV), as well as mitochondrial mass and mitochondrial membrane potential were not altered. Taken together, our results suggest that chronic MPH exposure at early age impairs glutamate uptake and Na+,K+-ATPase activity probably by decreasing in ATP levels observed in rat hippocampus.

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References

  1. Arnsten AF (2006) Stimulants: therapeutic actions in ADHD. Neuropsychopharmacology 31:2376–2383

    Article  CAS  PubMed  Google Scholar 

  2. Biederman J (2005) Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry 57:1215–1220

    Article  PubMed  Google Scholar 

  3. Hannestad J, Gallezot JD, Planeta-Wilson B, Lin SF, Williams WA, van Dyck CH et al (2010) Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol Psychiatry 68:854–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mohammadi MR, Mohammadzadeh S, Akhodzadeh S (2015) Memantine versus methylphenidate in children and adolescents with attention deficit hyperactivity disorder: a double-blind, randomized clinical tiral. Iranian J Psychiatry 10:106–114

    Google Scholar 

  5. Smith ME, Farah MJ (2011) Are prescription stimulants “smart pills”? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals. Psychological Bulleti 137:717–741

    Article  Google Scholar 

  6. Zito JM, Safer DJ, dos Reis S, Gardner JF, Boles M, Lynch F (2000) Trends in the prescribing of psychotropic medications to preschoolers. JAMA 283:1025–1030

    Article  CAS  PubMed  Google Scholar 

  7. Adriani W, Leo D, Greco D, Rea M, di Porzio U, Laviola G, Perrone-Capano C (2006) Methylphenidate administration to adolescent rats determines plastic changes on reward-related behavior and striatal gene expression. Neuropsychopharmacology 31:1946–1956

    Article  CAS  PubMed  Google Scholar 

  8. Andersen SL, Arvanitogiannis A, Pliakas AM, LeBlanc C, Carlezon WA Jr (2002) Altered responsiveness to cocaine in rats exposed to methylphenidate during development. Nat Neurosci 5:13–14

    Article  CAS  PubMed  Google Scholar 

  9. Carlezon WA Jr, Mague SD, Andersen SL (2003) Enduring behavioral effects of early exposure to methylphenidate in rats. Biol Psychiatry 54:1330–1337

    Article  CAS  PubMed  Google Scholar 

  10. Carlezon WA Jr, Konradi C (2004) Understanding the neurobiological consequences of early exposure to psychotropic drugs: linking behavior with molecules. Neuropharmacology 47:47–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mague SD, Andersen SL, Carlezon WA Jr (2005) Early developmental exposure to methylphenidate reduces cocaine-induced potentiation of brain stimulation reward in rats. Biol Psychiatry 57:120–125

    Article  CAS  PubMed  Google Scholar 

  12. Gonçalves J, Baptista S, Silva AP (2014) Psychostimulants and brain dysfunction: a review of the relevant neurotoxic effects. Neuropharmacology 87:135–149

    Article  PubMed  Google Scholar 

  13. Motaghinejad M, Motevalian M, Shabbab B (2016) Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats. Neurosci Lett 619:106–113

    Article  CAS  PubMed  Google Scholar 

  14. Réus GZ, Scaini G, Jeremias GC, Furlanetto CB, Morais MOS, Mello-Santos LM et al (2014) Brain apoptosis signaling pathways are regulated by methylphenidate in young and adult rats. Brain Res 1583:269–276

    Article  PubMed  Google Scholar 

  15. Sadasivan S, Pond BB, Pani AK, Qu C, Jiao Y, Smeyne RJ (2012) Methylphenidate exposure induces dopamine neuron loss and activation of microglia in the basal ganglia of mice. PLoS One 7:e33693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lagace DC, Yee JK, Bolanos CA, Eisch AJ (2006) Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis. Biol Psychiatry 60:1121–1130

    Article  CAS  PubMed  Google Scholar 

  17. Schmitz F, Pierozan P, Rodrigues AF, Biasibetti H, Coelho DM, Mussulini BH, Pereira MS, Parisi MM et al (2015) Chronic treatment with a clinically relevant dose of methylphenidate increases glutamate levels in cerebrospinal fluid and impairs glutamatergic homeostasis in prefrontal cortex of juvenile rats. Mol Neurobiol 53:2384–2396

    Article  PubMed  Google Scholar 

  18. Marks’ Basic Medical Biochemistry 2009: a clinical approach by Michael A Lieberman, Allan D. Marks, 3rd edition

  19. Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105

    Article  CAS  PubMed  Google Scholar 

  20. Segovia G, Porras A, Del Arco A et al (2001) Glutamatergic neurotransmission in aging: a critical perspective. Mech Ageing Dev 122:1–29

    Article  CAS  PubMed  Google Scholar 

  21. Nicholls DG (2008) Oxidative stress and energy crises in neuronal dysfunction. Ann N Y Acad Sci 1147:53–60

    Article  CAS  PubMed  Google Scholar 

  22. Maragakis NJ, Rothstein JD (2001) Glutamate transporters in neurologic disease. Arch Neurol 58:365–370

    Article  CAS  PubMed  Google Scholar 

  23. Maragakis NJ, Rothstein JD (2004) Glutamate transporters: animal models to neurologic disease. Neurobiol Dis 15:461–473

    Article  CAS  PubMed  Google Scholar 

  24. Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32:1–14

    Article  CAS  PubMed  Google Scholar 

  25. Zou J, Wang YX, Lü HZ, Lu PH, Xu XM (2010) Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons. Neurochem Int 56:577–584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rose EM, Koo JC, Antflick JE et al (2009) Glutamate transporter coupling to Na+,K+-ATPase. J Neurosci 29:8143–8155

    Article  CAS  PubMed  Google Scholar 

  27. Kaplan JH (2002) Biochemistry of Na+,K+-ATPase. Annu Ver Biochem 71:511–535

    Article  CAS  Google Scholar 

  28. Kurup AR, Kurup PA (2002) Membrane Na+,K+-ATPase mediated cascade in bipolar mood disorder, major depressive disorder, and schizophrenia—relationship to hemispheric dominance. Int J Neurosci 112:965–982

    Article  PubMed  Google Scholar 

  29. Wyse ATS, Streck EL, Worm P, Wajner A, Ritter F, Netto CA (2000) Preconditioning prevents the inhibition of Na+,K+-ATPase activity after brain ischemia. Neurochem Res 25:971–975

    Article  CAS  Google Scholar 

  30. Mobasheri A, Avila J, Cozar-Castellano I, Brownleader MD, Trevan M, Francis MJ et al (2000) Na+,K+-ATPase isozyme diversity; comparative biochemistry and physiological implications of novel functional interactions. Biosci Rep 20:51–91

    Article  CAS  PubMed  Google Scholar 

  31. Fukami G, Hashimoto K, Koike K, Okamura N, Shimizu E, Iyo M (2004) Effect of antioxidant N-acetyl-cysteine on behavioral changes and neurotoxicity in rats after administration of methanphetamine. Brain Res 1016:90–95

    Article  CAS  PubMed  Google Scholar 

  32. Porrino LJ, Lucignanai G (1987) Different patterns of local brain energy metabolism associated with high and low doses of methylphenidate. Relevance to its action in hyperactive children. Biol Psychiatry 22:126–138

    Article  CAS  PubMed  Google Scholar 

  33. Fagundes AO, Rezin GT, Zanette F, Grandi E, Assis LC, Dal-Pizzol F et al (2007) Chronic administration of methylphenidate activates mitochondrial respiratory chain in brain of young rats. Int J Dev Neurosci 25:47–51

    Article  CAS  PubMed  Google Scholar 

  34. Fagundes AO, Aguiar MR, Aguiar CS, Scaini G, Sachet MU, Bernhardt NM et al (2010a) Effect of acute and chronic administration of methylphenidate on mitochondrial respiratory chain in the brain of young rats. Neurochem Res 35:1675–1680

    Article  CAS  PubMed  Google Scholar 

  35. Fagundes AO, Scaini G, Santos PM, Sachet MU, Bernhardt NM, Rezin GT et al (2010b) Inhibition of mitochondrial respiratory chain in the brain of adult rats after acute and chronic administration of methylphenidate. Neurochem Res 35:405–411

    Article  CAS  PubMed  Google Scholar 

  36. Réus GZ, Scaini G, Furlanetto CB, Morais MO, Jeremias IC, Mello Santos LM et al (2013) Methylphenidate treatment leads to abnormalities on Krebs cycle enzymes in the brain of young and adult rats. Neurotoxic Res 24:251–257

    Article  Google Scholar 

  37. Réus GZ, Scaini G, Titus SE, Furlanetto CB, Wessler LB, Ferreira GK et al (2015) Methylphenidate increases glucose uptake in the brain of young and adult rats. Pharmacol Rep 67:1033–1040

    Article  PubMed  Google Scholar 

  38. Schmitz F, Scherer EB, da Cunha MJ, da Cunha AA, Lima DD, Delwing D et al (2012) Chronic methylphenidate administration alters antioxidant defenses and butyrylcholinesterase activity in blood of juvenile rats. Mol Cell Biochem 361:281–288

    Article  CAS  PubMed  Google Scholar 

  39. Gerasimov MR, Franceschi M, Volkow ND, Gifford A, Gatley SJ, Marsteller D et al (2000) Comparison between intraperitoneal and oral methylphenidate administration: a microdialysis and locomotor activity study. J Pharmacol Exp Ther 295:51–57

    CAS  PubMed  Google Scholar 

  40. Rice D, Barone S Jr (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 108:511–533

    Article  PubMed  PubMed Central  Google Scholar 

  41. Andreazza AC, Frey BN, Valvassori SS, Zanotto C, Gomes KM, Comim CM et al (2007) DNA damage in rats after treatment with methylphenidate. Prog Neuro-Psychopharmacol Biol Psychiatry 31:1282–1288

    Article  CAS  Google Scholar 

  42. Joseph MH, Marsden CA (1986) Amino acids and small peptides. In: Lim CF (ed) HPLC of small peptides. IRL Press, Oxford

    Google Scholar 

  43. Frizzo ME, Lara DR, Prokopiuk Ade S et al (2002) Guanosine enhances glutamate uptake in brain cortical slices at normal and excitotoxic conditions. Cell Mol Neurobiol 22:353–363

    Article  CAS  PubMed  Google Scholar 

  44. Chan KM, Delfert D, Junger KD (1986) Adirect colorimetric assay for Ca2+-stimulated ATPase activity. Anal Biochem 157:375–380

    Article  CAS  PubMed  Google Scholar 

  45. LeBel CP, Ali SF, McKee M, Bondy SC (1990) Organometal-induced increases in oxygen reactive species: the potential of 2′,7′-dichlorofluorescin diacetate as an index of neurotoxic damage. Toxicol Appl Pharmacol 104:17–24

    Article  CAS  PubMed  Google Scholar 

  46. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  47. Aksenov MY, Markesbery WR (2001) Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in Alzheimer’s disease. Neurosci Lett 302:141–145

    Article  CAS  PubMed  Google Scholar 

  48. Marklund SL (1985) Pyrogallol autoxidation. In: Handbook for oxygen radical research. CRC Press, Boca Raton, pp 243–247

  49. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  50. Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325–333

    Article  CAS  PubMed  Google Scholar 

  51. Witt KA, Mark KS, Hom S, Davis TP (2003) Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression. Am J Physiol Heart Circ Physiol 285:2820–2831

    Article  Google Scholar 

  52. Ramirez O, Jimenez E (2000) Opposite transitions of chick brain catalytically active cytosolic creatine kinase isoenzymes during development. Int J Dev Neurosci 18:815–823

    Article  CAS  PubMed  Google Scholar 

  53. Srere PA (1969) Citrate synthase. Methods Enzymol 13:3–11

    Article  CAS  Google Scholar 

  54. Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders JM et al (1985) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153:23–36

    Article  CAS  PubMed  Google Scholar 

  55. Rustin P, Chretien D, Bourgeron T, Gérard B, Rötig A, Saudubray JM et al (1994) Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 228:35–51

    Article  CAS  PubMed  Google Scholar 

  56. Keij JF, Bell-Prince C, Steinkamp JA (2000) Staining of mitochondrial membranes with 10-nonyl acridine orange, MitoFluor Green, and MitoTracker Green is affected by mitochondrial membrane potential altering drugs. Cytometry A 39:203–210

    Article  CAS  Google Scholar 

  57. Pendergrass W, Wolf N, Poot M (2004) Efficacy of MitoTracker Green (TM) and CMXRosamine to measure changes in mitochondrial membrane potentials in living cells and tissues. Cytometry A 61:162–169

    Article  CAS  PubMed  Google Scholar 

  58. Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356

    Article  CAS  PubMed  Google Scholar 

  59. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  60. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  61. Kuczenski R, Segal DS (2002) Exposure of adolescent rats to oral methylphenidate: preferential effects on extracellular norepinephrine and absence of sensitization and cross-sensitization to methamphetamine. J Neurosci 22:7264–7271

    CAS  PubMed  Google Scholar 

  62. Carlezon WA Jr, Duman RS, Nestler EJ (2005) The many faces of CREB. Trends Neurosci 28:436–44554

    Article  CAS  PubMed  Google Scholar 

  63. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM (2002) Neurobiology of depression. Neuron 34:13–25

    Article  CAS  PubMed  Google Scholar 

  64. Cepeda C, Levine MS (2006) Where do you think you are going? The NMDA-D1 receptor trap. Science’s Signal Transduction Knowledge Environment: STKE 2006:20–24

    Google Scholar 

  65. Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B et al (2006) Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry 60:1111–1120

    Article  CAS  PubMed  Google Scholar 

  66. Scherer EB, Matté C, Ferreira AG, Gomes KM, Comim CM, Mattos C et al (2009) Methylphenidate treatment increases Na+,K+-ATPase in the cerebrum of young and adult rats. J Neural Transm 116:1681–1687

    Article  CAS  PubMed  Google Scholar 

  67. Zakharova IO, Sokolova TV, Furaev VV, Rychkova MP, Avrova NF (2007) Effects of oxidative stress inducers, neurotoxins, and ganglioside GM1 on Na+,K+-ATPase in PC12 and brain synaptosomes. Zh Evol Biokhim Fiziol 43:148–154

    CAS  PubMed  Google Scholar 

  68. Pedersen WA, Cashman NR, Mattson MP (1999) The lipid peroxidation product 4-hydroxynonenal impairs glutamate and glucose transport and choline acetyltransferase activity in NSC-19 motor neuron cells. Exp Neurol 155:1–10

    Article  CAS  PubMed  Google Scholar 

  69. Schmitz F, Scherer EB, Machado FR, da Cunha AA, Tagliari B, Netto A, Wyse AT (2012) Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in cerebellum, striatum, and hippocampus of juvenile rats. Metab Brain Dis 27:605–612

    Article  CAS  PubMed  Google Scholar 

  70. Martins MR, Reinke A, Petronilho FC, Gomes KM, Dal-Pizzol F, Quevedo J (2006) Methylphenidate treatment induces oxidative stress in young rat brain. Brain Res 1078:189–197

    Article  CAS  PubMed  Google Scholar 

  71. Gomes KM, Petronilho FC, Mantovani M, Garbelotto T, Boeck CR, Dal-Pizzol F et al (2008) Antioxidant enzyme activities following acute and chronic methylphenidate treatment in young rats. Neurochem Res 33:1024–1027

    Article  CAS  PubMed  Google Scholar 

  72. Gomes KM, Inácio CG, Valvassori SS, Réus GZ, Boeck CR, Dal-Pizzol F et al (2009) Superoxide production after acute and chronic treatment with methylphenidate in young and adult rats. Neurosci Lett 465:95–98

    Article  CAS  PubMed  Google Scholar 

  73. Greenwood SM, Connolly CN (2007) Dendritic and mitochondrial changes during glutamate excitotoxicity. Neuropharmacology 53:891–898

    Article  CAS  PubMed  Google Scholar 

  74. Greenwood SM, Mizielinska SM, Frenguelli BG, Harvey J, Connoly CN (2007) Mitochondrial dysfunction and dendritic beading during neuronal toxicity. J Biol Chem 282:26235–26244

    Article  CAS  PubMed  Google Scholar 

  75. Scaini G, Fagundes AO, Rezin GT, Gomes KM, Zugno AI, Quevedo J et al (2008) Methylphenidate increases creatine kinase activity in the brain of young and adult rats. Life Sci 83:795–800

    Article  CAS  PubMed  Google Scholar 

  76. Haas H, Panula P (2003) The role of histamine and the tuberomamillary nucleus in the nervous system. Nature Reviews 4:121–130

    Article  CAS  PubMed  Google Scholar 

  77. Williams K (1994) Subunit-specific potentiation of recombinant N-methyl-D-aspartate receptors by histamine. Mol Pharmacol 46:531–541

    CAS  PubMed  Google Scholar 

  78. Leurs R, Bakker RA, Timmerman H, De Esch IJP (2005) The histamine H3 receptor from gene cloning to H3 receptor drugs. Nat Med 4:107–120

    CAS  Google Scholar 

  79. LaVoie MJ, Hastings TG (1999) Dopamine quinone formation and protein modification associated with the striatal neurotoxicity of methamphetamine: evidence against a role for extracellular dopamine. J Neurosci 19:1484–1491

    CAS  PubMed  Google Scholar 

  80. Page G, Peeters M, Najimi M et al (2001) Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes. J Neurochem 76:1282–1290

    Article  CAS  PubMed  Google Scholar 

  81. Spina MB, Cohen G (1989) Dopamine turnover and glutathione oxidation: implications for Parkinson disease. Proc Natl Acad Sci U S A 86:1398–1400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Adam-Vizi V (2005) Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain sources. Antioxid Redox Signal 7:1140–1149

    Article  CAS  PubMed  Google Scholar 

  83. Navarro A, Boveris A (2007) The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 292:670–686

    Article  Google Scholar 

  84. Gruno M, Peet N, Tein A et al (2008) Atrophic gastritis: deficient complex I of the respiratory chain in the mitochondria of corpus mucosal cells. J Gastroenterol 43:780–788

    Article  CAS  PubMed  Google Scholar 

  85. Sen T, Sen N, Jana S et al (2007) Depolarization and cardiolipin depletion in aged rat brain mitochondria: relationship with oxidative stress and electron transport chain activity. Neurochem Int 50:719–725

    Article  CAS  PubMed  Google Scholar 

  86. Beal MF (1992) Does impairment of energy metabolism result in excitotoxic neuronal death in neurological illnesses? Ann Neurol 31:119–130

    Article  CAS  PubMed  Google Scholar 

  87. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795

    Article  CAS  PubMed  Google Scholar 

  88. Schmitz F, Pierozan P, Rodrigues AF, Biasibetti H, Grunevald M, Petenuzzo L et al (2016) Methylphenidate causes behavioral impairments and neuron and astrocyte loss in the hippocampus of juvenile rats. Mol Neurobiol. doi:10.1007/s12035-016-9987-y

    Google Scholar 

  89. Akay AP, Kaya GÇ, Emiroglu NI, Aydin A, Monkul ES, Tasçi C et al (2006) Effects of long-term methylphenidate treatment: a pilot follow-up clinical and SPECT study. Prog Neuropsychopharmacology Biol Psychiatry 30:1219–1224

    Article  CAS  Google Scholar 

  90. Dafny N, Yang PB (2006) The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: a review of its locomotor effects. Brain Res Bull 68:393–405

    Article  CAS  PubMed  Google Scholar 

  91. Barker GR, Warburton EC (2008) NMDA receptor plasticity in the perirhinal and prefrontal cortices is crucial for the acquisition of long-term object-in-place associative memory. J Neurosci 28:2837–2844

    Article  CAS  PubMed  Google Scholar 

  92. Bergami M, Rimondini R, Santi S, Blum R, Götz M, Canossa M (2008) Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior. Proc Natl Acad Sci U S A 105:15570–15575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Heales SJ, Bolan˜os JP, Stewart VC (1999) Nitric oxide, mitochondria and neurological disease. Biochim Biophys Acta 1410:215–228

    Article  CAS  PubMed  Google Scholar 

  94. Blass JP (2001) Brain metabolism and brain disease: is metabolic deficiency the proximate cause of Alzheimer dementia? J Neurosci Res 66:851–856

    Article  CAS  PubMed  Google Scholar 

  95. Schurr A (2002) Energy metabolism, stress hormones and neural recovery from cerebral ischemia/hypoxia. Neurochem Int 41:1–8

    Article  CAS  PubMed  Google Scholar 

  96. Land JM, Morgan-Hughes JA, Hargreaves I et al (2004) Mitochondrial disease: a historical, biochemical, and London perspective. Neurochem Res 29:483–491

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by grants from Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq–Brazil).

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Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Felipe Schmitz, André F. Rodrigues, Helena Biasibetti, Mateus Grings, Guilhian Leipnitz & Angela T. S. Wyse

  2. Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Paula Pierozan, Bruna Zanotto, Guilhian Leipnitz & Angela T. S. Wyse

  3. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Daniella M. Coelho & Carmen R. Vargas

  4. Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    Angela T. S. Wyse

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  1. Felipe Schmitz
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Schmitz, F., Pierozan, P., Rodrigues, A.F. et al. Methylphenidate Decreases ATP Levels and Impairs Glutamate Uptake and Na+,K+-ATPase Activity in Juvenile Rat Hippocampus. Mol Neurobiol 54, 7796–7807 (2017). https://doi.org/10.1007/s12035-016-0289-1

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