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Neurochemical Research

, Volume 37, Issue 8, pp 1601–1614 | Cite as

Elevated Oxidative Stress and Decreased Antioxidant Function in the Human Hippocampus and Frontal Cortex with Increasing Age: Implications for Neurodegeneration in Alzheimer’s Disease

  • C. Venkateshappa
  • G. Harish
  • Anita Mahadevan
  • M. M. Srinivas BharathEmail author
  • S. K. Shankar
Original Paper

Abstract

Oxidative stress and mitochondrial damage are implicated in the evolution of neurodegenerative diseases. Increased oxidative damage in specific brain regions during aging might render the brain susceptible to degeneration. Previously, we demonstrated increased oxidative damage and lowered antioxidant function in substantia nigra during aging making it vulnerable to degeneration associated with Parkinson’s disease. To understand whether aging contributes to the vulnerability of brain regions in Alzheimer’s disease, we assessed the oxidant and antioxidant markers, glutathione (GSH) metabolic enzymes, glial fibrillary acidic protein (GFAP) expression and mitochondrial complex I (CI) activity in hippocampus (HC) and frontal cortex (FC) compared with cerebellum (CB) in human brains with increasing age (0.01–80 years). We observed significant increase in protein oxidation (HC: p = 0.01; FC: p = 0.0002) and protein nitration (HC: p = 0.001; FC: p = 0.02) and increased GFAP expression (HC: p = 0.03; FC: p = 0.001) with a decreasing trend in CI activity in HC and FC compared to CB with increasing age. These changes were associated with a decrease in antioxidant enzyme activities, such as superoxide dismutase (HC: p = 0.005), catalase (HC: p = 0.02), thioredoxin reductase (FC: p = 0.04), GSH reductase (GR) (HC: p = 0.005), glutathione-s-transferase (HC: p = 0.0001; FC: p = 0.03) and GSH (HC: p = 0.01) with age. However, these parameters were relatively unaltered in CB. We suggest that the regions HC and FC are subjected to widespread oxidative stress, loss of antioxidant function and enhanced GFAP expression during aging which might make them more susceptible to deranged physiology and selective neuronal degeneration.

Keywords

Aging Human brain Hippocampus Frontal cortex Protein oxidation Protein nitration Glutathione Glial fibrillary acidic protein Alzheimer’s disease 

Abbreviations

HC

Hippocampus

FC

Frontal cortex

CB

Cerebellum

AD

Alzheimer’s disease

PMI

Postmortem interval

MCI

Mild cognitive impairment

SOD

Superoxide dismutase

GSH

Glutathione

GR

Glutathione reductase

GPx

Glutathione peroxidase

GST

Glutathione-s-transferase

GFAP

Glial fibrillay acidic protein

GCL

Glutamylcysteine ligase

ThrR

Thioredoxin reductase

Notes

Acknowledgments

The authors thank the Human Brain Tissue Repository (HBTR), NIMHANS, Bangalore, India, for providing the human brain tissue samples required for the study. This study was financially supported by a grant from the Indian Council of Medical Research (ICMR IRIS ID No. 2009-07710) (to MMSB). VC gratefully acknowledges the financial support from Sri Siddhartha Medical College, Tumkur, India. GH is supported by a senior research fellowship from ICMR, India. The authors gratefully acknowledge the donors and their relatives for the kind gift of human brains for neurobiological studies.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • C. Venkateshappa
    • 1
  • G. Harish
    • 1
  • Anita Mahadevan
    • 2
  • M. M. Srinivas Bharath
    • 1
    Email author
  • S. K. Shankar
    • 2
  1. 1.Department of NeurochemistryNational Institute of Mental Health and Neurosciences (NIMHANS)BangaloreIndia
  2. 2.Department of NeuropathologyNational Institute of Mental Health and NeurosciencesBangaloreIndia

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