INVESTIGATING THE EFFECTS OF PHYSICAL ACTIVITY ON GENE EXPRESSION IN AUTISM SPECTRUM DISORDERS (REVIEW)
Keywords:
ASD, physical activity, BDNF, microRNA, gene expression, mitochondrial biogenesis, epigenetic modifications
Abstract
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.
Although the exact mechanisms and effective doses that cause significant changes in DNA methylation remain the subject of ongoing research, evidence supports that the combination of aerobic and strength training is important for altering DNA methylation patterns. Exercise affects BDNF chromatin modifications, BDNF exon IV promoter demethylation, and MeCP2 phosphorylation to stimulate BDNF mRNA and protein synthesis. Increased post-exercise levels of BDNF, an important neurotrophin that supports neurons, may improve neuroplasticity and reduce cognitive and behavioral impairment in ASD. Physical activity also accelerates mitochondrial biogenesis, promoting cellular resistance to reactive oxygen species under conditions of increased oxidative stress in ASD. Conclusion. Understanding the interplay between physical activity-induced gene expression modifications and their correlation with different exercise protocols and intensities is crucial. This provides a basis for the development of personalized exercise recommendations and strategies to reduce disease burden.
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51. Tremblay M.W., Jiang Y.H. DNA Methylation and Susceptibility to Autism Spectrum Disorder. Annual Review of Medicine, 2019, vol. 70, pp. 151–166. DOI: 10.1146/annurev-med-120417-091431
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53. Vakilzadeh G., Martinez-Cerdeño V. Pathology and Astrocytes in Autism. Neuropsychiatric Disease and Treatment, 2023, vol. 19, pp. 841–850. DOI: 10.2147/NDT.S390053
54. van Praag H. Neurogenesis and Exercise: Past and Future Directions. Neuromolecular Medicine, 2008, vol. 10 (2), pp. 128–140. DOI: 10.1007/s12017-008-8028-z
55. Wang S., Chen D., Yang Y. Effectiveness of Physical Activity Interventions for Core Symptoms of Autism Spectrum Disorder: A Systematic Review and Meta-analysis. Autism Re-search: Official Journal of the International Society for Autism Research, 2023, vol. 16 (9), pp. 1811–1824. DOI: 10.1002/aur.3004
56. Wang Z., Lu T., Li X. et al. Altered Expression of Brain-specific Autism-Associated miR-NAs in the Han Chinese Population. Frontiers in Genetics, 2022, vol. 13, art. 865881. DOI: 10.3389/fgene. 2022.865881
57. Woelfel J.R., Dudley-Javoroski S., Shields R.K. Precision Physical Therapy: Exercise, the Epigenome, and the Heritability of Environmentally Modified Traits. Physical Therapy, 2018, vol. 98 (11), pp. 946–952. DOI: 10.1093/ptj/pzy092
58. Wu X., Li W., Zheng Y. et al. Recent Progress on Relevant microRNAs in Autism Spectrum Disorders. International Journal of Molecular Sciences, 2020, vol. 21 (16), art. 5904. DOI: 10.3390/ijms21165904
59. Yang S., Liu Z., Xiong X. et al. Effects of Mini-Basketball Training Program on Social Communication Impairment and Executive Control Network in Preschool Children with Autism Spectrum Disorder. International Journal of Environmental Research and Public Health, 2021, vol. 18 (10), art. 5132. DOI: 10.3390/ijerph18105132
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61. Zong W., Lu X., Dong G. et al. Molecular Mechanisms of Exercise Intervention in Alleviating the Symptoms of Autism Spectrum Disorder: Targeting the Structural Alterations of Synapse. Frontiers in Psychiatry, 2023, vol. 14, art. 1096503. DOI: 10.3389/fpsyt.2023.1096503
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Published
2024-12-26
How to Cite
Protchenko, A., & Nenasheva, A. (2024). INVESTIGATING THE EFFECTS OF PHYSICAL ACTIVITY ON GENE EXPRESSION IN AUTISM SPECTRUM DISORDERS (REVIEW). Human. Sport. Medicine, 24(3), 42-52. https://doi.org/10.14529/hsm240305
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