Neurochemical Research

, Volume 37, Issue 2, pp 358–369 | Cite as

Increased Oxidative Damage and Decreased Antioxidant Function in Aging Human Substantia Nigra Compared to Striatum: Implications for Parkinson’s Disease

  • C. Venkateshappa
  • G. Harish
  • Rajeswara Babu Mythri
  • Anita Mahadevan
  • M. M. Srinivas Bharath
  • S. K. Shankar
Original Paper

Abstract

Parkinson’s disease (PD) is characterized by selective degeneration and loss of dopaminergic neurons in the substantia nigra (SN) of the ventral mid brain leading to dopamine depletion in the striatum. Oxidative stress and mitochondrial damage have been implicated in the death of SN neurons during the evolution of PD. In our previous study on human PD brains, we observed that compared to SN, striatum was significantly protected against oxidative damage and mitochondrial dysfunction. To understand whether brain aging contributes to the vulnerability of midbrain to neurodegeneration in PD compared to striatum, we assessed the status of oxidant and antioxidant markers, glutathione metabolic enzymes, glial fibrillary acidic protein (GFAP) expression and mitochondrial complex I(CI) activity in SN (n = 23) and caudate nucleus (n = 24) during physiological aging in human brains. We observed a significant increase in protein oxidation (P < 0.001), loss of CI activity (P = 0.04) and increased astrocytic proliferation indicated by GFAP expression (P < 0.001) in SN compared to CD with increasing age. These changes were attributed to significant decrease in antioxidant function represented by superoxide dismutase (SOD) (P = 0.03), glutathione (GSH) peroxidase (GPx) (P = 0.02) and GSH reductase (GR) (P = 0.03) and a decreasing trend in total GSH and catalase with increasing age. However, these parameters were relatively unaltered in CD. We propose that SN undergoes extensive oxidative damage, loss of antioxidant and mitochondrial function and increased GFAP expression during physiological aging which might make it more vulnerable to neurotoxic insults thus contributing to selective degeneration during evolution of PD.

Keywords

Aging Human brain Substantia nigra Caudate nucleus Oxidative protein damage Glutathione Glial fibrillary acidic protein Parkinson’s disease 

Abbreviations

PD

Parkinson’s disease

SN

Substantia nigra

CI

Mitochondrial complex I

GSH

Glutathione reduced

PMI

Postmortem interval

CD

Caudate nucleus

3-NT

3-Nitrotyrosine

GFAP

Glial fibrillary acidic protein

SOD

Superoxide dismutase

GST

Glutathione-s-transferase

GR

Glutathione reductase

GPx

Glutathione peroxidase

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • C. Venkateshappa
    • 1
  • G. Harish
    • 1
  • Rajeswara Babu Mythri
    • 1
  • Anita Mahadevan
    • 2
  • M. M. Srinivas Bharath
    • 1
  • S. K. Shankar
    • 2
  1. 1.Departments of NeurochemistryNational Institute of Mental Health and Neurosciences (NIMHANS)BangaloreIndia
  2. 2.Departments of NeuropathologyNational Institute of Mental Health and Neurosciences (NIMHANS)BangaloreIndia

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