oxidative damage, inflammation, low glutathione redox status in the autism brain

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Evidence of oxidative damage and inflammation associated with low

glutathione redox status in the autism brain.

<http://www.ncbi.nlm.nih.gov/pubmed/22781167>

Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, Frye RE, SJ.

Transl Psychiatry. 2012 Jul 10;2:e134.

Despite increasing evidence of oxidative stress in the pathophysiology

of autism, most studies have not evaluated biomarkers within specific

brain regions, and the functional consequences of oxidative stress

remain relatively understudied. We examined frozen samples from the

cerebellum and temporal cortex (Brodmann area 22 (BA22)) from

individuals with autism and unaffected controls (n=15 and n=12 per

group, respectively). Biomarkers of oxidative stress, including reduced

glutathione (GSH), oxidized glutathione (GSSG) and glutathione

redox/antioxidant capacity (GSH/GSSG), were measured. Biomarkers of

oxidative protein damage (3-nitrotyrosine; 3-NT) and oxidative DNA

damage (8-oxo-deoxyguanosine; 8-oxo-dG) were also assessed. Functional

indicators of oxidative stress included relative levels of

3-chlorotyrosine (3-CT), an established biomarker of a chronic

inflammatory response, and aconitase activity, a biomarker of

mitochondrial superoxide production. Consistent with previous studies on

plasma and immune cells, GSH and GSH/GSSG were significantly decreased

in both autism cerebellum (P<0.01) and BA22 (P<0.01). There was a

significant increase in 3-NT in the autism cerebellum and BA22 (P<0.01).

Similarly, 8-oxo-dG was significantly increased in autism cerebellum and

BA22 (P<0.01 and P=0.01, respectively), and was inversely correlated

with GSH/GSSG in the cerebellum (P<0.01). There was a significant

increase in 3-CT levels in both brain regions (P<0.01), whereas

aconitase activity was significantly decreased in autism cerebellum

(P<0.01), and was negatively correlated with GSH/GSSG (P=0.01).

Together, these results indicate that decreased GSH/GSSG

redox/antioxidant capacity and increased oxidative stress in the autism

brain may have functional consequence in terms of a chronic inflammatory

response, increased mitochondrial superoxide production, and oxidative

protein and DNA damage.