Department of Medical Biology, Medical University Plovdiv, Plovdiv, Bulgaria.
Clinic of Pediatrics, Saint George University Hospital, Plovdiv, Bulgaria.
Curr Top Med Chem. 2021;21(11):985-994. doi: 10.2174/1568026621666210521142131.
Although Autism Spectrum Disorder (ASD) is considered a heterogeneous neurological disease in childhood, a growing body of evidence associates it with mitochondrial dysfunction explaining the observed comorbidities.
The aim of this study is to identify variations in cellular bioenergetics and metabolism dependent on mitochondrial function in ASD patients and healthy controls using Peripheral Blood Mononuclear Cells (PBMCs). We hypothesized that PBMCs may reveal the cellular pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease.
PBMC from children with ASD and a control group of the same age and gender were isolated. All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian children is selected. Bioenergetic and metabolic studies of isolated PBMCs are performed with a Seahorse XFp analyzer.
Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity (by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the control group. These results can contribute to a better understanding of the underlying causes of ASD, which is crucial for selecting a successful treatment.
The current study, for the first time, provides a functional analysis of cell bioenergetics and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities that do not allow mitochondria to adapt and meet the increased energetic requirements of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead to the discovery of new approaches for nutrition and therapy.
自闭症谱系障碍（ASD）被认为是一种儿童期异质性神经疾病，但越来越多的证据将其与线粒体功能障碍联系起来，从而解释了观察到的合并症。
本研究旨在使用外周血单核细胞（PBMC）鉴定 ASD 患者和健康对照组中依赖于线粒体功能的细胞生物能量学和代谢变化。我们假设 PBMC 可能揭示细胞病理学，并提供伴随疾病的生物能量学和代谢变化的证据。
从 ASD 儿童和年龄、性别相同的对照组中分离 PBMC。所有患者均接受了深入的临床评估。选择了一个经过充分表征的保加利亚儿童队列。使用 Seahorse XFp 分析仪对分离的 PBMC 进行生物能量学和代谢研究。
我们的数据表明，ASD 患者的 PBMC 具有更高的呼吸储备能力（增加 27.5%）、更高的最大呼吸（增加 67%）和对 DMNQ 诱导的氧化应激的适应性反应改变。此外，我们还证明了对脂肪酸的强烈依赖和细胞代谢重新编程能力受损。这些特征在对照组中没有观察到。这些结果有助于更好地理解 ASD 的潜在原因，这对于选择成功的治疗方法至关重要。
本研究首次提供了一组保加利亚 ASD 患者细胞生物能量学和代谢变化的功能分析。它揭示了不允许线粒体适应和满足细胞增加的能量需求的生理异常。线粒体与 ASD 之间的联系尚未完全理解，但这可能会导致发现新的营养和治疗方法。
