Brain region-specific glutathione redox imbalance in autism

[Guest guest]

Brain region-specific glutathione redox imbalance in autism.

<http://www.ncbi.nlm.nih.gov/pubmed/22528835>

Chauhan A, Audhya T, Chauhan V.

Neurochem Res. 2012 Aug;37(8):1681-9.

Autism is a heterogeneous, behaviorally defined neurodevelopmental

disorder. Recently, we reported a brain region-specific increase in

lipid peroxidation, and deficits in mitochondrial electron transport

chain complexes in autism, suggesting the role of oxidative stress and

mitochondrial dysfunction in the pathophysiology of autism. However, the

antioxidant status of the brain is not known in autism. Glutathione is a

major endogenous antioxidant that plays a crucial role in protecting

cells from exogenous and endogenous toxins, particularly in the central

nervous system. The present study examines the concentrations of

glutathione (GSH, reduced form; and GSSG, oxidized form) and the redox

ratio of GSH to GSSG (marker of oxidative stress) in different regions

of brains from autistic subjects and age-matched control subjects. In

the cerebellum and temporal cortex from subjects with autism, GSH levels

were significantly decreased by 34.2 and 44.6 %, with a concomitant

increase in the levels of GSSG by 38.2 and 45.5 %, respectively, as

compared to the control group. There was also a significant decrease in

the levels of total GSH (tGSH) by 32.9 % in the cerebellum, and by

43.1 % in the temporal cortex of subjects with autism. In contrast,

there was no significant change in GSH, GSSG and tGSH levels in the

frontal, parietal and occipital cortices in autism versus control group.

The redox ratio of GSH to GSSG was also significantly decreased by

52.8 % in the cerebellum and by 60.8 % in the temporal cortex of

subjects with autism, suggesting glutathione redox imbalance in the

brain of individuals with autism. These findings indicate that autism is

associated with deficits in glutathione antioxidant defense in selective

regions of the brain. We suggest that disturbances in brain glutathione

homeostasis may contribute to oxidative stress, immune dysfunction and

apoptosis, particularly in the cerebellum and temporal lobe, and may

lead to neurodevelopmental abnormalities in autism.