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.

摘要

线粒体和免疫功能障碍通常与自闭症谱系障碍 (ASD) 的病因有关。在这里，我们首次研究了 ASD 严重程度与新鲜分离的血小板中线粒体呼吸频率以及分离的中性粒细胞中烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 氧化酶 (NOX) 的活性之间的关系。我们还验证了高压氧疗法 (HBOT) 对线粒体和免疫功能以及 ASD 严重程度指标的影响。从三个年龄匹配的男性组（对照组 (Norm-N)、自闭症 (Aut-N) 和自闭症 + HBOT (Aut-H)）收集血液样本；N  = 每组 10 个）。使用高分辨率呼​​吸测定法，我们发现 Aut-N 血小板中的常规基础呼吸、复合物 I 和复合物 I + II 依赖性氧化磷酸化率显着受损。同样，嗜中性粒细胞免疫反应的缺陷通过较低的耗氧率和吞噬性 NOX 产生的活性氧 (ROS) 来证明。发现 ASD 相关的行为结果与血小板的线粒体生物能参数以及中性粒细胞中 NOX 介导的活性有中等程度的相关性。HBOT 无法改善线粒体功能障碍或抵消 ASD 相关的行为缺陷。尽管 HBOT 改善了免疫反应的一项措施；即，NOX 介导的超氧化物爆发，这与组间反复感染趋势的显着变化无关。总之，我们的数据表明在血小板和中性粒细胞中可以检测到 ASD 相关的线粒体和免疫缺陷。我们还没有发现任何证据表明 HBOT 可以显着改善 ASD 相关的生理或行为表型。