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.
Acknowledgements
The authors are thankful to both Ms. Salma El-Hosseiny and Ms. Nourhan Karam of Zewail City of Science and Technology for some technical help during their training in SSA’s laboratory. SSA and EAA would like to acknowledge the support provided by Horizon 2020, COST Action CA15203 ‘MitoEAGLE’.
Author contributions
EAA conducted metabolic studies, analysed data and wrote the initial draft of the manuscript. EAZ designed the clinical study, described clinical data, and along with RME and WYY obtained ethical approvals as well as written consents, recruited subjects, conducted behavioural assessments, administered surveys and HBOT protocols, and collected blood samples. MA handled blood samples to isolate platelets and neutrophils. AMM performed EPR studies. SSA perceived, designed, and supervised metabolic studies in addition to analysing data, interpreting results, and writing the manuscript in its final form. All authors revised the manuscript and approved its submission in the current form.
Disclosure statement
No competing interest declared for any of the contributing authors.