Autism spectrum disorder (ASD)-associated mitochondrial deficits are revealed in children’s platelets but unimproved by hyperbaric oxygen therapy

Abstract

Mitochondrial and immune dysfunctions are often implicated in the aetiology of autism spectrum disorder (ASD). Here, we studied for the first time the relationship between ASD severity measures and mitochondrial respiratory rates in freshly isolated platelets as well as the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in isolated neutrophils. We also verified the impact of hyperbaric oxygen therapy (HBOT) on mitochondrial and immune functions as well as on ASD severity measures. Blood samples were collected from three age-matched male groups (Control (Norm-N), autistic (Aut-N), and autistic + HBOT (Aut-H); N = 10 per group). Using high resolution respirometry, we found that routine basal respiration, complex I- and complex I + II-dependent oxidative phosphorylation rate were significantly impaired in Aut-N platelets. Similarly, deficits in immune response of neutrophils were evidenced through lower rates of oxygen consumption and reactive oxygen species (ROS) production by phagocytic NOX. ASD-related behavioural outcomes were found to moderately correlate with platelets’ mitochondrial bioenergetic parameters as well as with NOX-mediated activity in neutrophils. HBOT was not able to improve mitochondrial dysfunctions or to counteract ASD-related behavioral deficits. Although HBOT improved one measure of the immune response; namely, NOX-mediated superoxide burst, this was not associated with significant changes in trends of recurrent infections between groups. Taken together, our data suggest that ASD-associated mitochondria and immune deficits are detectable in platelets and neutrophils. We also found no evidence that HBOT confers any significant improvement of ASD-associated physiological or behavioural phenotypes.