Cellular Bioenergetic and Metabolic Changes in Patients with Autism Spectrum Disorder

Abstract

Background: 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. Introduction: 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. Method: 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 was selected. Bioenergetic and metabolic studies of isolated PBMCs were performed with a Seahorse XFp analyzer. Result: 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. Conclusion: 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.

Autism spectrum disorders: an impaired glycolysis induces an ATP deficiency and a reduced cell respiration

“…In agreement with the former findings, higher respiratory capacities and complex IV activity were reported in a lymphoblastoid cell line derived from an autistic child (Hassan et al 2021). Finally, peripheral blood mononuclear cells indicate that patients with ASD have increased respiratory reserve capacity and maximal respiration (Gevezova et al 2021).…”

Urine manganese, cadmium, lead, arsenic, and selenium among autism spectrum disorder children in Kuala Lumpur

“…This information further validates the hypothesis that the development of ASD may be associated with exposure to As. As may affect cellular metabolic processes, ASD was once described as a metabolic disorder characterised by alterations in the metabolism of glucose, amino acids and lipids ( Gevezova et al, 2021 ; Du et al, 2022 ). On the other hand, some studies reported no significant association between exposure to As via measurement in hair samples and the development of ASD in children ( De Palma et al., 2012 ; Fido & Al-Saad, 2005 ).…”

Association between heavy metals exposure (cadmium, lead, arsenic, mercury) and child autistic disorder: a systematic review and meta-analysis

“…Subgroup analysis of testing sources showed that compared with the healthy controls, ASD children had higher arsenic concentrations in their hair, urine, and blood ( P < 0.05), which further validated the hypothesis that arsenic exposure might be associated with the occurrence of ASD. ASD was once considered to be a metabolic disease, characterized by a metabolic disorder of glucose, lipid, and amino acid ( 84 , 85 ). Arsenic could affect the cellular metabolic processes ( 86 ).…”