Neuroprotective effects of various doses of topiramate against methylphenidate-induced oxidative stress and inflammation in isolated rat amygdala: the possible role of CREB/BDNF signaling pathway.
Methylphenidate (MPH) abuse damages brain cells. The neuroprotective effects of topiramate (TPM) have been reported previously, but its exact mechanism of action still remains unclear. This study investigated the in vivo role of various doses of TPM in the protection of rat amygdala cells against methylphenidate-induced oxidative stress and inflammation. Seventy adult male rats were divided into seven groups. Groups 1 and 2 received normal saline (0.7 ml/rat) and MPH (10 mg/kg), respectively, for 21 days. Groups 3, 4, 5, 6, and 7 were concurrently treated with MPH (10 mg/kg) and TPM (10, 30, 50, 70, and 100 mg/kg), respectively, for 21 days. elevated plus maze (EPM) was used to assess motor activity disturbances. In addition, oxidative, antioxidantand inflammatory factors and CREB, Ak1, CAMK4, MAPK3, PKA, BDNF, and c FOS gene levels were measured by RT-PCR, and also, CREB and BDNF protein levels were measured by WB in isolated amygdalae. MPH significantly disturbed motor activity and TPM (70 and 100 mg/kg) neutralized its effects. MPH significantly increased lipid peroxidation, mitochondrial GSSG levels and IL-1β and TNF-α level and CAMK4 gene expression in isolated amygdala cells. In contrast, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities and CREB, BDNF Ak1, MAPK3, PKA, BDNF, and c FOS expression significantly decreased. The various doses of TPM attenuated these effects of MPH. It seems that TPM can be used as a neuroprotective agent and is a good candidate against MPH-induced neurodegeneration.
Razi Drug Research Center and Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Hemmat High Way, Beside Milad Tower, 14496-14525, Tehran, Iran.
Majid
M
Motaghinejad
Razi Drug Research Center and Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Hemmat High Way, Beside Milad Tower, 14496-14525, Tehran, Iran. motevalian.m@iums.ac.ir.
Manijeh
M
Motevalian
Department of Immunology, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Reza
R
Falak
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
Mansour
M
Heidari
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
Mahshid
M
Sharzad
Oncopathology Research Center and Department of Pathology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Elham
E
Kalantari
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000139:chemically induced / Q000517:prevention & control*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008774:Methylphenidate / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D000077236:Topiramate
D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D000077236:Topiramate; D008774:Methylphenidate; D005632:Fructose; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D050882:CREB-Binding Protein; D005978:Glutathione
Amygdala; BDNF; Inflammation; Methylphenidate; Oxidative stress; Topiramate
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