Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism.
Mitochondria play important roles in generation of free radicals, ATP formation, and in apoptosis. We studied the levels of mitochondrial electron transport chain (ETC) complexes, that is, complexes I, II, III, IV, and V, in brain tissue samples from the cerebellum and the frontal, parietal, occipital, and temporal cortices of subjects with autism and age-matched control subjects. The subjects were divided into two groups according to their ages: Group A (children, ages 4-10 years) and Group B (adults, ages 14-39 years). In Group A, we observed significantly lower levels of complexes III and V in the cerebellum (p<0.05), of complex I in the frontal cortex (p<0.05), and of complexes II (p<0.01), III (p<0.01), and V (p<0.05) in the temporal cortex of children with autism as compared to age-matched control subjects, while none of the five ETC complexes was affected in the parietal and occipital cortices in subjects with autism. In the cerebellum and temporal cortex, no overlap was observed in the levels of these ETC complexes between subjects with autism and control subjects. In the frontal cortex of Group A, a lower level of ETC complexes was observed in a subset of autism cases, that is, 60% (3/5) for complexes I, II, and V, and 40% (2/5) for complexes III and IV. A striking observation was that the levels of ETC complexes were similar in adult subjects with autism and control subjects (Group B). A significant increase in the levels of lipid hydroperoxides, an oxidative stress marker, was also observed in the cerebellum and temporal cortex in the children with autism. These results suggest that the expression of ETC complexes is decreased in the cerebellum and the frontal and temporal regions of the brain in children with autism, which may lead to abnormal energy metabolism and oxidative stress. The deficits observed in the levels of ETC complexes in children with autism may readjust to normal levels by adulthood.
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. abha.chauhan@opwdd.ny.gov
Abha
A
Chauhan
Feng
F
Gu
Musthafa M
MM
Essa
Jerzy
J
Wegiel
Kulbir
K
Kaur
William Ted
WT
Brown
Ved
V
Chauhan
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001321:Autistic Disorder / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D011180:Postmortem Changes; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
D008054:Lipid Peroxides; D009097:Multienzyme Complexes; D017382:Reactive Oxygen Species
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