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01-04-2017 | ORIGINAL ARTICLE

Topiramate Confers Neuroprotection Against Methylphenidate-Induced Neurodegeneration in Dentate Gyrus and CA1 Regions of Hippocampus via CREB/BDNF Pathway in Rats

Authors: Majid Motaghinejad, Manijeh Motevalian, Mohammad Abdollahi, Mansour Heidari, Zahra Madjd

Published in: Neurotoxicity Research | Issue 3/2017

Abstract

Methylphenidate (MPH) abuse can cause serious neurological damages. The neuroprotective effects of topiramate (TPM) have been reported already, but its mechanism of action still remains unclear. The current study evaluates in vivo role of CREB/BDNF in TPM protection of the rat hippocampal cells from methylphenidate-induced apoptosis, oxidative stress, and inflammation. A total of 60 adult male rats were divided into six groups. Groups 1 and 2 received normal saline (0.7 ml/rat) and MPH (10 mg/kg) respectively for 14 days. Groups 3 and 4 were concurrently treated with MPH (10 mg/kg) and TPM 50 and 100 mg/kg respectively for 14 days. Groups 5 and 6 were treated with 50 and 100 mg/kg TPM only respectively. After drug administration, open field test (OFT) was used to investigate motor activity. The hippocampus was then isolated and the apoptotic, antiapoptotic, oxidative, antioxidant, and inflammatory factors were measured. Expression of the total and phosphorylated CREB and BDNF in gene and protein levels, and gene expression of Ak1, CaMK4, MAPK3, PKA, and c-Fos levels were also measured. MPH significantly decreased motor activity in OFT. TPM (50 and 100 mg/kg) decreased MPH-induced motor activity disturbance. Additionally, MPH significantly increased Bax protein level, CaMK4 gene expression, lipid peroxidation, catalase activity, mitochondrial GSH, IL-1β, and TNF-α levels in isolated hippocampal cells. Also CREB, in total and phosphorylated forms, BDNF and Bcl-2 protein levels, Ak1, MAPK3, PKA and c-Fos gene expression, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities decreased significantly by MPH. TPM (50 and 100 mg/kg), both in the presence and absence of MPH, attenuated the effects of MPH. Immunohistochemistry data showed that TPM increased localization of the total and phosphorylated forms of CREB in dentate gyrus (DG) and CA1 areas of the hippocampus. It seems that TPM can be used as a neuroprotective agent against apoptosis, oxidative stress, and neuroinflammation induced by frequent use of MPH. This might be probably mediated by the CREB/BDNF and their upstream signaling pathways.

Agarwal NB, Agarwal NK, Mediratta PK, Sharma KK (2011) Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice. Seizure 20(3):257–262CrossRefPubMed

Aguiar AS, Castro AA, Moreira EL, Glaser V, Santos AR, Tasca CI et al (2011) Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. Mech Ageing Dev 132(11):560–567CrossRefPubMed

Aliev G, Smith MA, Obrenovich ME, Jack C, Perry G (2003) Role of vascular hypoperfusion-induced oxidative stress and mitochondria failure in the pathogenesis of Alzheimer disease. Neurotox Res 5(7):491–504CrossRefPubMed

Almeida R, Manadas B, Melo C, Gomes J, Mendes C, Graos M et al (2005) Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ 12(10):1329–1343CrossRefPubMed

Almeida S, Cunha-Oliveira T, Laço M, Oliveira CR, Rego AC (2010) Dysregulation of CREB activation and histone acetylation in 3-nitropropionic acid-treated cortical neurons: prevention by BDNF and NGF. Neurotox Res 17(4):399–405CrossRefPubMed

Amador FC, Santos MS, Oliveira CR (2001) Lipid peroxidation and aluminium effects on the cholinergic system in nerve terminals. Neurotox Res 3(3):223–233CrossRefPubMed

Armaǧan A, Kutluhan S, Yılmaz M, Yılmaz N, Bülbül M, Vural H et al (2008) Topiramate and vitamin E modulate antioxidant enzyme activities, nitric oxide and lipid peroxidation levels in pentylenetetrazol-induced nephrotoxicity in rats. Basic Clin Pharmacol Toxicol 103(2):166–170CrossRefPubMed

Arnone D (2005) Review of the use of topiramate for treatment of psychiatric disorders. Ann General Psychiatry 16(4):1–8

Arundine M, & Tymianski M (2003) Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Arundine M et al Cell Calcium 34(5): 325–337.

Blendy JA (2006) The role of CREB in depression and antidepressant treatment. Biol Psychiatry 59(12):1144–1150CrossRefPubMed

Bongiovanni B, De Lorenzi P, Ferri A, Konjuh C, Rassetto M, De Duffard AE et al (2007) Melatonin decreases the oxidative stress produced by 2, 4-dichlorophenoxyacetic acid in rat cerebellar granule cells. Neurotox Res 11(2):93–99CrossRefPubMed

Brown JM, Yamamoto BK (2003) Effects of amphetamines on mitochondrial function: role of free radicals and oxidative stress. Pharmacol Ther 99(1):45–53CrossRefPubMed

Cagetti E, Baicy KJ, Olsen RW (2004) Topiramate attenuates withdrawal signs after chronic intermittent ethanol in rats. Neuroreport 15(1):207–210CrossRefPubMed

Carlezon WA, Duman RS, Nestler EJ (2005) The many faces of CREB. Trends Neurosci 28(8):436–445CrossRefPubMed

Challman TD, Lipsky JJ (2000) Methylphenidate: its pharmacology and uses. Mayo Clin Proc 75:711–721CrossRefPubMed

Cheng X, Li M (2014) Effect of topiramate on apoptosis-related protein expression of hippocampus in model rats with Alzheimers disease. Eur Rev Med Pharmacol Sci 18(16):761–768PubMed

Cippitelli A, Damadzic R, Frankola K, Goldstein A, Thorsell A, Singley E et al (2010) Alcohol-induced neurodegeneration, suppression of transforming growth factor-β, and cognitive impairment in rats: prevention by group II metabotropic glutamate receptor activation. Biol Psychiatry 67(9):823–830CrossRefPubMed

Davids E, Zhang K, Tarazi FI, Baldessarini RJ (2002) Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning. Psychopharmacology 160(1):92–98CrossRefPubMed

Demirci S, Kutluhan S, Nazıroğlu M, Uğuz AC, Yürekli VA, Demirci K (2013) Effects of selenium and topiramate on cytosolic Ca2+ influx and oxidative stress in neuronal PC12 cells. Neurochem Res 38(1):90–97CrossRefPubMed

Dudley JT, Sirota M, Shenoy M, Pai RK, Roedder S, Chiang AP et al (2011) Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease. Sci Transl Med 3:96ra76–96ra76CrossRefPubMedPubMedCentral

Dworkin S, Mantamadiotis T (2010) Targeting CREB signalling in neurogenesis. Expert Opin Ther Targets 14(8):869–879CrossRefPubMed

Erickson MA, Banks WA (2011) Cytokine and chemokine responses in serum and brain after single and repeated injections of lipopolysaccharide: multiplex quantification with path analysis. Brain Behav Immun 25(8):1637–1648CrossRefPubMedPubMedCentral

Fortunato JJ, Agostinho FR, RÉus GZ, Petronilho FC, Dal-Pizzol F, Quevedo J (2006) Lipid peroxidative damage on malathion exposure in rats. Neurotox Res 9(1):23–28CrossRefPubMed

François J, Koning E, Ferrandon A, Nehlig A (2006) The combination of topiramate and diazepam is partially neuroprotective in the hippocampus but not antiepileptogenic in the lithium-pilocarpine model of temporal lobe epilepsy. Epilepsy Res (3):147–163

Gao H-L, Xu H, Xin N, Zheng W, Chi Z-H, Wang Z-Y (2011) Disruption of the CaMKII/CREB signaling is associated with zinc deficiency-induced learning and memory impairments. Neurotox Res 19(4):584–591CrossRefPubMed

Garnett WR (2000) Clinical pharmacology of topiramate: a review. Epilepsia 41(5):61–65CrossRef

Gibbs JE, Walker MC, Cock HR (2006) Levetiracetam: antiepileptic properties and protective effects on mitochondrial dysfunction in experimental status epilepticus. Epilepsia 47(3):469–478CrossRefPubMed

Guo W, Crossey EL, Zhang L, Zucca S, George OL, Valenzuela CF et al (2011) Alcohol exposure decreases CREB binding protein expression and histone acetylation in the developing cerebellum. PLoS One 6(5):e19351–e19351CrossRefPubMedPubMedCentral

Huang W, Cao J, Liu X, Meng F, Li M, Chen B et al (2015) AMPK plays a dual role in regulation of CREB/BDNF pathway in mouse primary hippocampal cells. J Mol Neurosci 56(4):782–788CrossRefPubMed

Huss M, Lehmkuhl U (2001) Methylphenidate and substance abuse: a review of pharmacology, animal, and clinical studies. J Atten Disord 6:S65–S71

Johansson LH, Borg LH (1988) A spectrophotometric method for determination of catalase activity in small tissue samples. Anal Biochem 174(1):331–336CrossRefPubMed

Johnson BA, Ait-Daoud N, Wang X-Q, Penberthy JK, Javors MA, Seneviratne C et al (2013) Topiramate for the treatment of cocaine addiction: a randomized clinical trial. JAMA psychiatry 70(12):1338–1346CrossRefPubMed

Juárez J, Guerrero-Álvarez Á (2015) Effects of methylphenidate and atomoxetine on impulsivity and motor activity in preadolescent rats prenatally-treated with alcohol. Behav Neurosci 129(6):756CrossRefPubMed

Khan S, Liberzon I (2004) Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD. Psychopharmacology 172(2):225–229CrossRefPubMed

Kitagawa K (2007) CREB and cAMP response element-mediated gene expression in the ischemic brain. FEBS J 274(13):3210–3217CrossRefPubMed

Klein-Schwartz W (2002) Abuse and toxicity of methylphenidate. Curr Opin Pediatr 14(2):219–223CrossRefPubMed

Koçer A, Memişoğullari R, Domaç FM, Ilhan A, Koçer E, Okuyucu Ş et al (2009) IL-6 levels in migraine patients receiving topiramate. Pain Practice 9(3):375–379CrossRefPubMed

Kuczenski R, Segal DS (2001) Locomotor effects of acute and repeated threshold doses of amphetamine and methylphenidate: relative roles of dopamine and norepinephrine. J Pharmacol Exp Ther 296(3):876–883PubMed

Kutluhan S, Nazıroğlu M, Çelik Ö, Yılmaz M (2009) Effects of selenium and topiramate on lipid peroxidation and antioxidant vitamin levels in blood of pentylentetrazol-induced epileptic rats. Biol Trace Elem Res 129(1–3):181–189CrossRefPubMed

Lau JW, Senok S, Stadlin A (2000) Methamphetamine-induced oxidative stress in cultured mouse astrocytes. Ann N Y Acad Sci 914:146–156CrossRefPubMed

Lee B, Butcher GQ, Hoyt KR, Impey S, Obrietan K (2005) Activity-dependent neuroprotection and cAMP response element-binding protein (CREB): kinase coupling, stimulus intensity, and temporal regulation of CREB phosphorylation at serine 133. J Neurosci 25(5):1137–1148CrossRefPubMed

Lonze BE, Ginty DD (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35(4):605–623CrossRefPubMed

Madjd Z, Akbari ME, Zarnani AH, Khayamzadeh M, Kalantari E, Mojtabavi N (2013) Expression of EMSY, a novel BRCA2-link protein, is associated with lymph node metastasis and increased tumor size in breast carcinomas. Asian Pac J Cancer Prev 15(4):1783–1789CrossRef

Mao X-Y, Cao Y-G, Ji Z, Zhou H-H, Liu Z-Q, Sun H-L (2015) Topiramate protects against glutamate excitotoxicity via activating BDNF/TrkB-dependent ERK pathway in rodent hippocampal neurons. Prog Neuro-Psychopharmacol Biol Psychiatry 60:11–17CrossRef

Marquette C, Linard C, Galonnier M, Van Uye A, Mathieu J, Gourmelon P et al (2003) IL-1 β, TNF α and IL-6 induction in the rat brain after partial-body irradiation: role of vagal afferents. Int J Radiat Biol 79(10):777–785CrossRefPubMed

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(1):189–197CrossRefPubMed

Mattson MP (2007) Calcium and neurodegeneration. Aging Cell 6(1):337–350CrossRefPubMed

Mayr B, Montminy M (2001) Transcriptional regulation by the phosphorylation-dependent factor CREB. Nature reviews Nat Rev Mol Cell Biol 2(8):599–609CrossRefPubMed

Meredith GE, Callen S, Scheuer DA (2002) Brain-derived neurotrophic factor expression is increased in the rat amygdala, piriform cortex and hypothalamus following repeated amphetamine administration. Brain Res 949(1–2):218–227CrossRefPubMed

Molina-Hernández M, Téllez-Alcántara NP, Olivera-Lopez JI, Jaramillo MT (2010) Antidepressant-like or anxiolytic-like actions of topiramate alone or co-administered with intra-lateral septal infusions of neuropeptide Y in male Wistar rats. Peptides 31(6):1184–1189CrossRefPubMed

Motaghinejad M, Karimian M, Motaghinejad O, Shabab B, Yazdani I, Fatima S (2015a) Protective effects of various dosage of Curcumin against morphine induced apoptosis and oxidative stress in rat isolated hippocampus. Pharmacol Rep 67(2):230–235CrossRefPubMed

Motaghinejad M, Karimian SM, Motaghinejad O, Shabab B, Asadighaleni M, Fatima S (2015b) The effect of various morphine weaning regimens on the sequelae of opioid tolerance involving physical dependency, anxiety and hippocampus cell neurodegeneration in rats. Fundam Clin Pharmacol 29(3):299–309CrossRefPubMed

Motaghinejad M, Motevalian M (2016) Involvement of AMPA/kainate and GABA A receptors in topiramate neuroprotective effects against methylphenidate abuse sequels involving oxidative stress and inflammation in rat isolated hippocampus. Eur J Pharmacol 784:181–191CrossRefPubMed

Motaghinejad M, Motevalian M, Ebrahimzadeh A (2015c) Reduction of methylphenidate induced anxiety, depression and cognition impairment by various doses of venlafaxine in rat. Int J Prev Med 784:181–191

Motaghinejad M, Motevalian M, Larijani SF, Khajehamedi Z (2015d) Protective effects of forced exercise against methylphenidate-induced anxiety, depression and cognition impairment in rat. Adv Biomed Res 27(4):134. doi:10.4103/2277-9175 CrossRef

Motaghinejad M, Motevalian M, Shabab B (2016c) Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats. Neurosci Lett 21(619):106–113CrossRef

Motaghinejad M, Motevalian M, Shabab B (2016a) Neuroprotective effects of various doses of topiramate against methylphenidate induced oxidative stress and inflammation in rat isolated hippocampus. Clin Exp Pharmacol Physiol 43(3):360–371CrossRefPubMed

Motaghinejad M, Motevalian M, Shabab B (2016b) Possible involvements of glutamate and adrenergic receptors on acute toxicity of methylphenidate in isolated hippocampus and cerebral cortex of adult rats. Fundam Clin Pharmacol 14. doi:10.1111/fcp.12250

Motaghinejad M, Motevalian M, Shabab B, & Fatima S (2016e) Effects of acute doses of methylphenidate on inflammation and oxidative stress in isolated hippocampus and cerebral cortex of adult rats. J Neural Transm (Vienna) Sep 28.

Motaghinejad M, Seyedjavadein Z, Motevalian M, Asadi M (2016d) The neuroprotective effect of lithium against high dose methylphenidate: possible role of BDNF. Neurotoxicology 56:40–54CrossRefPubMed

Mula M, Pini S, Cassano GB (2007) The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence. J Clin Psychopharmacol 27(3):263–272CrossRefPubMed

Nazıroğlu M, Kutluhan S, Uğuz AC, Çelik Ö, Bal R, Butterworth PJ (2009) Topiramate and vitamin E modulate the electroencephalographic records, brain microsomal and blood antioxidant redox system in pentylentetrazol-induced seizure of rats. J Membr Biol 229(3):131–140CrossRefPubMed

Nazirolu M, Kutluhan S, Yilmaz M (2008) Selenium and topiramate modulates brain microsomal oxidative stress values, Ca2+ − ATPase activity, and EEG records in pentylentetrazol-induced seizures in rats. J Membr Biol 225(1–3):39–49CrossRef

Noh M-R, Kim SK, Sun W, Park SK, Choi HC, Lim JH et al (2006) Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal rats. Exp Neurol 201(2):470–478CrossRefPubMed

Oncken C, Arias AJ, Feinn R, Litt M, Covault J, Sofuoglu M et al (2014) Topiramate for smoking cessation: a randomized, placebo-controlled pilot study. Nicotine Tob Res 16(3):288–296CrossRefPubMed

Pandey SC, Chartoff EH, Carlezon WA, Zou J, Zhang H, Kreibich AS et al (2005) CREB gene transcription factors: role in molecular mechanisms of alcohol and drug addiction. Alcohol Clin Exp Res 29(2):176–184CrossRefPubMed

Park HJ, Kim HJ, Park HJ, Ra J, Zheng LT, Yim SV et al (2008) Protective effect of topiramate on kainic acid–induced cell death in mice hippocampus. Epilepsia 49(1):163–167CrossRefPubMed

Patrick KS, Markowitz JS (1997) Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention-deficit hyperactivity disorder. Hum Psychopharmacol 12(2):527–546CrossRef

Peng J, Sarkar S, Chang SL (2012) Opioid receptor expression in human brain and peripheral tissues using absolute quantitative real-time RT-PCR. Drug Alcohol Depend 124(3):223–228CrossRefPubMedPubMedCentral

Pomierny-Chamioło L, Moniczewski A, Wydra K, Suder A, Filip M (2013) Oxidative stress biomarkers in some rat brain structures and peripheral organs underwent cocaine. Neurotox Res 23(1):92–102CrossRefPubMed

Poulsen CF, Simeone TA, Maar TE, Smith-Swintosky V, White HS, Schousboe A (2004) Modulation by topiramate of AMPA and kainate mediated calcium influx in cultured cerebral cortical, hippocampal and cerebellar neurons. Neurochem Res 29(1):275–282CrossRefPubMed

Qian J, Noebels JL (2003) Topiramate alters excitatory synaptic transmission in mouse hippocampus. Epilepsy Res 55(3):225–233CrossRefPubMed

Raskin P, Donofrio P, Rosenthal N, Hewitt D, Jordan D, Xiang J et al (2004) Topiramate vs placebo in painful diabetic neuropathy analgesic and metabolic effects. Neurology 63(5):865–873CrossRefPubMed

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. Neurotox Res 24(2):251–257CrossRefPubMed

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

Réus GZ, Stringari RB, Ribeiro KF, Ferraro AK, Vitto MF, Cesconetto P et al (2011) Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain. Behav Brain Res 221(1):166–171CrossRefPubMed

Saeed U, Karunakaran S, Meka DP, Koumar RC, Ramakrishnan S, Joshi SD et al (2009) Redox activated MAP kinase death signaling cascade initiated by ASK1 is not activated in female mice following MPTP: novel mechanism of neuroprotection. Neurotox Res 16(2):116–126CrossRefPubMed

Schubert S, Brandl U, Brodhun M, Ulrich C, Spaltmann J, Fiedler N et al (2005) Neuroprotective effects of topiramate after hypoxia–ischemia in newborn piglets. Brain Res 1058(1–2):129–136CrossRefPubMed

Schwarting RK, Sedelis M, Hofele K, Auburger GW, Huston JP (1999) Strain-dependent recovery of open-field behavior and striatal dopamine deficiency in the mouse MPTP model of Parkinson’s disease. Neurotox Res 1(1):41–56CrossRefPubMed

Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE (2000) An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 41:3–9CrossRef

Silva AJ, Kogan JH, Frankland PW, Kida S (1998) CREB and memory. Annu Rev Neurosci 21:127–148CrossRefPubMed

Siniscalchi A, Bonci A, Biagio Mercuri N, Pirritano D, Squillace A, De Sarro G et al (2015) The role of topiramate in the management of cocaine addiction: a possible therapeutic option. Curr Neuropharmacol 13(6):815–818CrossRefPubMedPubMedCentral

Tagaya H (2010) Methylphenidate: pharmacology, indication and potential of abuse. Nihon Rinsho 68(8):1550–1555PubMed

Terranova C, Rizzo V, Rajan T, Naro A, Ahmad A, Ghilardi M et al (2016) 58. Repetitive transcranial magnetic stimulation induces neuroprotection via activating CaMKIIα-CREB-Bcl-2 pathway in rat brain. Clin Neurophysiol 127:e146CrossRef

Vendruscolo LF, Izídio GS, Takahashi RN, Ramos A (2008) Chronic methylphenidate treatment during adolescence increases anxiety-related behaviors and ethanol drinking in adult spontaneously hypertensive rats. Behav Pharmacol 19(1):21CrossRefPubMed

Wang B, Zhao J, Yu M, Meng X, Cui X, Zhao Y et al (2014) Disturbance of intracellular calcium homeostasis and CaMKII/CREB signaling is associated with learning and memory impairments induced by chronic aluminum exposure. Neurotox Res 26(3):52–63CrossRefPubMed

Wei Z, Chigurupati S, Bagsiyao P, Henriquez A, Chan SL (2009) The brain uncoupling protein UCP4 attenuates mitochondrial toxin-induced cell death: role of extracellular signal-regulated kinases in bioenergetics adaptation and cell survival. Neurotox Res 16(1):14–29CrossRefPubMed

Wells PG, Bhatia S, Drake DM, Miller-Pinsler L (2016) Fetal oxidative stress mechanisms of neurodevelopmental deficits and exacerbation by ethanol and methamphetamine. Birth Defects Res C Embryo Today: Reviews 10(2):108–130CrossRef

Woo NH, Teng HK, Siao C-J, Chiaruttini C, Pang PT, Milner TA, et al. (2005) Activation of p75NTR by proBDNF facilitates hippocampal long-term depression.Nat Neurosci 8(8): 1069–1077.

Yamamoto BK, Raudensky J (2008) The role of oxidative stress, metabolic compromise, and inflammation in neuronal injury produced by amphetamine-related drugs of abuse. J NeuroImmune Pharmacol 3(4):203–217CrossRefPubMedPubMedCentral

Zuo D, Lin L, Liu Y, Wang C, Xu J, Sun F et al (2016) Baicalin attenuates ketamine-induced neurotoxicity in the developing rats: involvement of PI3K/Akt and CREB/BDNF/Bcl-2 pathways. Neurotox Res 30(2):1–14CrossRef

Title: Topiramate Confers Neuroprotection Against Methylphenidate-Induced Neurodegeneration in Dentate Gyrus and CA1 Regions of Hippocampus via CREB/BDNF Pathway in Rats
Authors: Majid Motaghinejad
Manijeh Motevalian
Mohammad Abdollahi
Mansour Heidari
Zahra Madjd
Publication date: 01-04-2017
Publisher: Springer US
Published in: Neurotoxicity Research / Issue 3/2017
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-016-9695-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Topiramate Confers Neuroprotection Against Methylphenidate-Induced Neurodegeneration in Dentate Gyrus and CA1 Regions of Hippocampus via CREB/BDNF Pathway in Rats

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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