title: Evaluation of markers of oxidative stress, antioxidant function and astrocytic proliferation in the striatum and frontal cortex of Parkinson's disease brains.
abstract: Dopaminergic neurons die in Parkinson's disease (PD) due to oxidative stress and mitochondrial dysfunction in the substantia nigra (SN). We evaluated if oxidative stress occurs in other brain regions like the caudate nucleus (CD), putamen (Put) and frontal cortex (FC) in human postmortem PD brains (n = 6). While protein oxidation was elevated only in CD (P < 0.05), lipid peroxidation was increased only in FC (P < 0.05) and protein nitration was unchanged in PD compared to controls. Interestingly, mitochondrial complex I (CI) activity was unaffected in PD compared to controls. There was a 3-5 fold increase in the total glutathione (GSH) levels in the three regions (P < 0.01 in FC and CD; P < 0.05 in Put) but activities of antioxidant enzymes catalase, superoxide dismutase, glutathione reductase and glutathione-s-tranferase were not increased. Total GSH levels were elevated in these areas because of decreased activity of gamma glutamyl transpeptidase (γ-GT) (P < 0.05) activity suggesting a decreased breakdown of GSH. There was an increase in expression of glial fibrillary acidic protein (GFAP) (P < 0.001 in FC; P < 0.05 in CD) and glutathione peroxidase (P < 0.05 in CD and Put) activity due to proliferation of astrocytes. We suggest that increased GSH and astrocytic proliferation protects non-SN brain regions from oxidative and mitochondrial damage in PD.
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neurosciences, # 2900, Hosur Road, Bangalore, 560029, Karnataka, India.
authors.forename: Rajeswara Babu
authors.initials: RB
authors.lastname: Mythri
authors.forename: C
authors.initials: C
authors.lastname: Venkateshappa
authors.forename: G
authors.initials: G
authors.lastname: Harish
authors.forename: Anita
authors.initials: A
authors.lastname: Mahadevan
authors.forename: Uday B
authors.initials: UB
authors.lastname: Muthane
authors.forename: T C
authors.initials: TC
authors.lastname: Yasha
authors.forename: M M
authors.initials: MM
authors.lastname: Srinivas Bharath
authors.forename: S K
authors.initials: SK
authors.lastname: Shankar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D015415:Biomarkers