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Publication Detail

Title: Deficits in bioenergetics and impaired immune response in granulocytes from children with autism.

Authors: Napoli, Eleonora; Wong, Sarah; Hertz-Picciotto, Irva; Giulivi, Cecilia

Published In Pediatrics, (2014 May)

Abstract: Despite the emerging role of mitochondria in immunity, a link between bioenergetics and the immune response in autism has not been explored. Mitochondrial outcomes and phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst were evaluated in granulocytes from age-, race-, and gender-matched children with autism with severity scores of ≥7 (n = 10) and in typically developing (TD) children (n = 10). The oxidative phosphorylation capacity of granulocytes was 3-fold lower in children with autism than in TD children, with multiple deficits encompassing ≥1 Complexes. Higher oxidative stress in cells of children with autism was evidenced by higher rates of mitochondrial reactive oxygen species production (1.6-fold), higher mitochondrial DNA copy number per cell (1.5-fold), and increased deletions. Mitochondrial dysfunction in children with autism was accompanied by a lower (26% of TD children) oxidative burst by PMA-stimulated reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase and by a lower gene expression (45% of TD children's mean values) of the nuclear factor erythroid 2-related factor 2 transcription factor involved in the antioxidant response. Given that the majority of granulocytes of children with autism exhibited defects in oxidative phosphorylation, immune response, and antioxidant defense, our results support the concept that immunity and response to oxidative stress may be regulated by basic mitochondrial functions as part of an integrated metabolic network.

PubMed ID: 24753527 Exiting the NIEHS site

MeSH Terms: Child; Child Development Disorders, Pervasive/immunology*; Energy Metabolism/physiology*; Granulocytes/immunology*; Humans; Oxidative Phosphorylation; Oxygen Consumption/physiology; Superoxides/metabolism

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