Neurochemical Research

, Volume 38, Issue 1, pp 186–200

Alteration in Glutathione Content and Associated Enzyme Activities in the Synaptic Terminals but not in the Non-synaptic Mitochondria from the Frontal Cortex of Parkinson’s Disease Brains

  • G. Harish
  • Anita Mahadevan
  • M. M. Srinivas Bharath
  • S. K. Shankar
Original Paper

DOI: 10.1007/s11064-012-0907-x

Cite this article as:
Harish, G., Mahadevan, A., Srinivas Bharath, M.M. et al. Neurochem Res (2013) 38: 186. doi:10.1007/s11064-012-0907-x

Abstract

Altered redox dynamics contribute to physiological aging and Parkinson’s disease (PD). This is reflected in the substantia nigra (SN) of PD patients as lowered antioxidant levels and elevated oxidative damage. Contrary to this observation, we previously reported that non-SN regions such as caudate nucleus and frontal cortex (FC) exhibited elevated antioxidants and lowered mitochondrial and oxidative damage indicating constitutive protective mechanisms in PD brains. To investigate whether the sub-cellular distribution of antioxidants could contribute to these protective effects, we examined the distribution of antioxidant/oxidant markers in the neuropil fractions [synaptosomes, non-synaptic mitochondria and cytosol] of FC from PD (n = 9) and controls (n = 8). In the control FC, all the antioxidant activities [Superoxide dismutase (SOD), glutathione (GSH), GSH peroxidase (GPx), GSH-S-transferase (GST)] except glutathione reductase (GR) were the highest in cytosol, but several fold lower in mitochondria and much lower in synaptosomes. However, FC synaptosomes from PD brains had significantly higher levels of GSH (p = 0.01) and related enzymes [GPx (p = 0.02), GR (p = 0.06), GST (p = 0.0001)] compared to controls. Conversely, mitochondria from the FC of PD cases displayed elevated SOD activity (p = 0.02) while the GSH and related enzymes were relatively unaltered. These changes in the neuropil fractions were associated with unchanged or lowered oxidative damage. Further, the mitochondrial content in the synaptosomes of both PD and control brains was ≥five-fold lower compared to the non-synaptic mitochondrial fraction. Altered distribution of oxidant/antioxidant markers in the neuropil fractions of the human brain during aging and PD has implications for (1) degenerative and protective mechanisms (2) distinct antioxidant mechanisms in synaptic terminals compared to other compartments.

Keywords

Parkinson’s diseaseFrontal cortexNeuropilSynaptosomesMitochondriaOxidative stressGlutathione

Abbreviations

PD

Parkinson’s disease

SN

Substantianigra

FC

Frontal cortex

GSH

Glutathione reduced

PMI

Postmortem interval

3-NT

3-nitrotyrosine

GFAP

Glial fibrillary acidic protein

SOD

Superoxide Dismutase

GST

Glutathione-s-transferase

GR

Glutathione reductase

GP

Xglutathione peroxidase

ns mito

Non-synaptic mitochondria

syn mito

Synaptic mitochondria

cyto

Cytosol

CS

Citrate synthase

MDH

Malate dehydrogenase

SDH

Succinate dehydrogenase

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • G. Harish
    • 1
  • Anita Mahadevan
    • 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