Objectives: Recently, we reported brain region-specific deficit in the protein expression of mitochondrial ETC complexes in the cerebellum and cortices from frontal and temporal regions from the children with autism. The aim of this study was to compare the activities of mitochondrial ETC complexes and PDH enzyme in the frontal cerebral cortex from subjects with autism and age-matched controls.
Methods: Frozen human brain tissues (frontal cerebral cortex) of autistic and age-matched control subjects were obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland. Mitochondria were isolated from frontal cortex tissues according to the differential centrifugation method. Protein concentrations of mitochondria in samples were estimated by bicinchoninic acid protein assay kit. The activities of mitochondrial ETC complexes I, II, III, IV, V, and PDH enzyme were analyzed using microplate assay kits.
Results: The results showed deficiencies of activities of ETC complexes I and V to be most prevalent in autism that was observed in 43% of autism subjects, followed by deficiency in activity of complex III in 29% and of complexes II and IV in 14% of autistic subjects when compared with control group. Multiple deficiencies of ETC complexes were observed in 29 % of autistic subjects. PDH activity was also significantly reduced in 57% of autistic subjects as compared to control group.
Conclusions: These results suggest that autism is associated with mitochondrial abnormalities in the brain that may lead to oxidative stress and abnormal energy metabolism.
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See more of: Biological Mechanisms