title: Oxidative stress and mitochondrial dysfunction are the underlying events of dopaminergic neurodegeneration in homocysteine rat model of Parkinson's disease.
abstract: Homocysteine (Hcy) when injected intranigrally in rat caused parkinsonian behavioural phenotypes and loss of nigral dopaminergic neurons but the underlying mechanisms of neurotoxicity remains elusive. In the present study, we focused on oxidative stress as one of the mechanisms of neurotoxicity in Hcy-induced hemiparkinsonian rat model. Unilateral intranigral infusion of Hcy (1.0 μmol in 2 μl) caused inhibition of mitochondrial complex-I activity, decrease in the level of striatal dopamine, loss of midbrain dopaminergic neurons, and motor abnormalities. Hcy caused oxidative stress in the nigrostriatal pathway, with increase in generation of hydroxyl radicals, depletion in the level of reduced glutathione and enhanced activity of antioxidant enzymes (superoxide dismutase and catalase). Our results provided the evidence of critical involvement of oxidative stress as one of the mechanisms underlying Hcy-induced dopaminergic neurotoxicity in nigrostriatal pathway. As oxidative stress is one of the prime mechanisms of neurodegeneration in different animal models of Parkinson's disease, and since Hcy caused equivalent parkinsonian pathologies in rat model, the present study proclaims Hcy-induced rat model as a viable rodent model of Parkinson's disease.
authors.affiliation: Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Bhattacharjee
authors.affiliation: Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India. Electronic address: anupomborahh@gmail.com.
authors.forename: Anupom
authors.initials: A
authors.lastname: Borah
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D042967:Electron Transport Complex I / Q000187:drug effects / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D006710:Homocysteine; D042967:Electron Transport Complex I; D004298:Dopamine
keywords: Antioxidant enzymes; Dopamine; Glutathione; HPLC-ECD; Hyperhomocysteinemia; Mitochondrial complex; Neurodegeneration