Investigating the effects of physical activity on gene expression in autism spectrum disorders (review)

Aim. This comprehensive review aims to dissect the molecular mechanisms through which physical activity influences gene expression in individuals with autism spectrum disorders (ASD), focusing on the effects on the clinical manifestations of autism. Materials and methods. A comprehensive literature review was conducted, encompassing studies published between 2007 and 2024, using databases such as PubMed, Google Scholar, and ScienceDirect. Results. The analysis reveals that physical activity enhances gene expression, thus mitigating ASD symptoms. Notably, it influences microRNA profiles and DNA methylation patterns, increases BDNF expression, and enhances mitochondrial biogenesis. Through the alternation of microRNA profiles, physical activity may indirectly affect the expression of ASD-related genes, including those involved in neurogenesis, synaptogenesis, neuronal migration, oxidative stress, and neuro­inflammation. For example, miR-146a contributes to the disruption of synaptic transmission, inhibition of neuronal migration, and augmentation of the inflammatory response. After exercise, circulating miR-146a levels were reduced by 49%. Furthermore, miR-146a is a promising diagnostic biomarker and potential therapeutic target in ASD, given its abnormal expression in both brain tissue and body fluids of ASD patients. Physical activity has a marked effect on DNA methylation patterns, potentially modulating gene expression. Certain loci throughout the genome are abnormally methylated in people with ASD compared to controls. These changes may affect the expression of genes critical for neurodevelopment and synaptic function.