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.
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Abbreviations
- PD:
-
Parkinson’s disease
- AD:
-
Alzheimer’s disease
- SN:
-
Substantia nigra
- CI:
-
Mitochondrial complex I
- ROS:
-
Reactive oxygen species
- GSH:
-
Glutathione reduced
- PMI:
-
Postmortem interval
- FC:
-
Frontal cortex
- CD:
-
Caudate nucleus
- Put:
-
Putamen
- SN:
-
Substantia Nigra
- 3-NT:
-
3-nitrotyrosine
- GFAP:
-
Glial Fibrillary acidic protein
- SOD:
-
Superoxide dismutase
- GST:
-
Glutathione-s-transferase
- GR:
-
Glutathione reductase
- γ-GCL:
-
Gamma glutamyl cysteine ligase
- γGT:
-
Gamma glutamyl transpeptidase
- GPx:
-
Glutathione peroxidase
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Acknowledgments
This work was financially supported by the Department of Science and Technology (DST) (fast-track grant no.SR/FT/L-152/2005), India and Indian Council of Medical Research (ICMR IRIS ID No. 2009-07710), India, both to MMSB. RM was supported by a senior research fellowship from Council of Scientific and Industrial Research (CSIR), India. GH is a senior research fellow of ICMR, India. We thank all the donors and their relatives for donating human brain tissue samples for this study. Human brain tissue for the study is sourced from Human Brain Tissue Repository for Neurobiological Studies (A National Research Facility), Department of Neuropathology, NIMHANS, Bangalore 560 029.
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11064_2011_471_MOESM1_ESM.tif
Supplementary Fig. 1 Analysis of markers of oxidative/nitrosative stress in the SN region of postmortem human brains (PD (representative PD sample no. 6 in Table 1) and controls (C)). a Total GSH was estimated in C vs PD in SN. b Estimation of lipid peroxidation in SN from C and PD samples. c Total protein extract after DNP-derivatization (~10 μg) in SN from C and PD samples were spotted on nitrocellulose membrane in triplicate followed by anti-DNP western blot (Oxyblot) and the quantitative plot of anti-DNP signal (normalized with β-actin signal) in C and PD SN regions is shown. d Total protein extracts (~25 μg) from SN from C and PD samples were spotted on nitrocellulose membrane followed by anti-3NT western blot and the quantitative plot of 3-NT signal (normalized with β-actin signal) in C and PD SN region are shown. All the samples were tested for oxidative markers in multiple experiments (n ≥ 3). **P < 0.01 and ***P < 0.001 in PD compared to C (TIFF 2409 kb)
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Mythri, R.B., Venkateshappa, C., Harish, G. et al. Evaluation of Markers of Oxidative Stress, Antioxidant Function and Astrocytic Proliferation in the Striatum and Frontal Cortex of Parkinson’s Disease Brains. Neurochem Res 36, 1452–1463 (2011). https://doi.org/10.1007/s11064-011-0471-9
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DOI: https://doi.org/10.1007/s11064-011-0471-9