Mapping of Oxidative Stress Damage in Autistic Brain

Background: Increased oxidative stress and associated protein modification measured by 3 nitrotyrosine (3-NT) has been reported in over fifty different pathologies. We have previously shown increased 3-NT levels in autistic cerebella.

Objectives: The aim of the current study was to identify brain regions in autism with the highest level of oxidative damage by mapping the levels of 3-NT across brain regions.

Methods: The levels of 3-NT were measured by ELISA in brain homogenates prepared from frozen brain samples. The levels of 3-NT were analyzed in 13 individual brain regions of an autistic male donor (age 14.3 years; PMI 9 hours) and matched control male donor (age, 14.5 years; PMI, 16 hours).

Results: In contrast to control brain where the levels of 3-NT were uniformly across regions examined, ranging from 2.86 pmol/g to 10.54 pmol/g, in autistic brain the 3-NT levels were variable ranging 1.68pmol/g to 151.39pmol/g. Several autistic brain regions showed increased 3NT levels; the highest 3-NT levels were observed in Wernicke’s area > cerebellar hemisphere > orbitofrontal gyrus > cerebellar vermis > hippocampus. The increase, expressed as percent control, ranged from 4955 in Wernicke’s area to 286 in hippocampus. There was no increase in 3-NT levels in prefrontal cortex, caudate, cingulate gyrus, corpus callosum, corona radiate, putamen and thalamus in autistic brain.
Conclusions: The increase in oxidative stress damage in autism appears to be brain region-specific and most pronounced in brain areas associated with the speech processing, sensory and motor coordination, emotional and social behavior and memory, a pattern consistent with clinical manifestations of autism. At this point it is not clear whether this pattern of oxidative stress is common to a subclass of autism spectrum. These data, however, suggest that we may begin to relate oxidative changes to autistic pathology and perhaps also identify new brain regions involved in autism by mapping oxidative stress damage across brain regions.