Neurochemical Research

, Volume 36, Issue 8, pp 1452–1463 | Cite as

Evaluation of Markers of Oxidative Stress, Antioxidant Function and Astrocytic Proliferation in the Striatum and Frontal Cortex of Parkinson’s Disease Brains

  • Rajeswara Babu Mythri
  • C. Venkateshappa
  • G. Harish
  • Anita Mahadevan
  • Uday B. Muthane
  • T. C. Yasha
  • M. M. Srinivas Bharath
  • S. K. Shankar
Original Paper
First Online:
Accepted:

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.

Keywords

Parkinson’s disease Protein oxidation Protein nitration Glutathione Glial fibrillary acidic protein Frontal cortex Caudate nucleus Putamen 

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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Notes

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.

Supplementary material

11064_2011_471_MOESM1_ESM.tif (2.4 mb)
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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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Rajeswara Babu Mythri
    • 1
  • C. Venkateshappa
    • 1
  • G. Harish
    • 1
  • Anita Mahadevan
    • 2
  • Uday B. Muthane
    • 3
    • 4
  • T. C. Yasha
    • 2
  • M. M. Srinivas Bharath
    • 1
  • S. K. Shankar
    • 2
  1. 1.Department of NeurochemistryNational Institute of Mental Health and NeurosciencesBangaloreIndia
  2. 2.Department of NeuropathologyNational Institute of Mental Health and NeurosciencesBangaloreIndia
  3. 3.Department of NeurologyNational Institute of Mental Health and NeurosciencesBangaloreIndia
  4. 4.Parkinson’s and Ageing Research FoundationKudlu Village, Singasandra Post, BangaloreIndia

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