ИССЛЕДОВАНИЕ ВЛИЯНИЯ ФИЗИЧЕСКОЙ АКТИВНОСТИ НА ЭКСПРЕССИЮ ГЕНОВ ПРИ РАССТРОЙСТВАХ АУТИСТИЧЕСКОГО СПЕКТРА (ОБЗОР ЛИТЕРАТУРЫ)
Ключевые слова:
РАС, физическая активность, BDNF, микроРНК, экспрессия генов, биогенез митохондрий, эпигенетические модификации
Аннотация
Цель: анализ современных данных о молекулярных механизмах влияния физической активности на экспрессию генов у лиц с расстройствами аутистического спектра (РАС) и воздействии физических упражнений на клинические проявления аутизма. Материалы и методы. Проанализированы литературные источники с использованием баз данных PubMed, Google Scholar, Sciencedirect по исследованиям, опубликованным в научных журналах с 2007 по 2024 год. Результаты. Физическая активность усиливает экспрессию генов, положительно влияющих на проявления РАС через различные механизмы, включая изменение профиля микроРНК и паттернов метилирования ДНК, увеличение экспрессии BDNF, усиление биогенеза митохондрий. Изменяя профили микроРНК, физическая активность может косвенно влиять на экспрессию генов, связанных с РАС, в том числе тех, которые участвуют в нейрогенезе, синаптогенезе, миграции нейронов, окислительном стрессе, нейровоспалении. Например, miR-146a принимает участие в нарушении синаптической передачи при РАС, ингибировании миграции нейронов и усилении воспалительной реакции. После тренировки уровень циркулирующей miR-146a снижался на 49 %. Кроме того, miR-146a является перспективным диагностическим биомаркером и потенциальной терапевтической мишенью при РАС, учитывая его аномальную экспрессию как в тканях головного мозга, так и в жидкостях организма пациентов с РАС. Физическая активность оказывает заметное влияние на паттерны метилирования ДНК, потенциально модулируя экспрессию генов. Определенные локусы по всему геному аномально метилированы у людей с РАС по сравнению с контрольной группой. Эти изменения могут влиять на экспрессию генов, критически важных для нейроразвития и синаптической функции. Хотя точные механизмы и эффективные дозы, вызывающие значительные изменения в метилировании ДНК, остаются предметом продолжающихся исследований, имеющиеся данные подтверждают, что сочетание аэробных и силовых тренировок имеет важное значение для изменения структуры метилирования ДНК. Физические упражнения влияют на модификации хроматина BDNF, деметилирование ДНК промотора BDNF IV и фосфорилирование MeCP2 для стимуляции синтеза мРНК и белка BDNF. Увеличение уровня BDNF, важного нейротрофина, поддерживающего нейроны, после физической нагрузки может улучшить нейропластичность и снизить когнитивные и поведенческие нарушения при РАС. Также физическая активность ускоряет образование митохондрий, способствуя устойчивости клеток к активным формам кислорода в условиях повышенного окислительного стресса при РАС. Заключение. Экспрессия генов, связанных с РАС, модифицируется под воздействием физической активности, и корреляция этих изменений с результатами различных протоколов упражнений и их интенсивностью могут проложить путь к разработке индивидуальных рекомендаций по упражнениям, адаптированным к индивидуальным потребностям здоровья и стратегиям уменьшения проявлений заболевания.
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47. Shi P., Zhang Z., Feng X. Effect of Physical Exercise in Real-world Settings on Executive Function of Atypical Children: A Systematic Review and Meta-analysis. Child: Care, Health and Development, 2024, vol. 50 (1), art. e13182. DOI: 10.1111/cch.13182
48. Talebizadeh Z., Butler M.G., Theodoro M.F. Feasibility and Relevance of Examining Lymphoblastoid Cell Lines to Study Role of MicroRNAs in Autism. Autism Research: Official Journal of the International Society for Autism Research, 2008, vol. 1 (4), pp. 240–250. DOI: 10.1002/aur.33
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23. Leisman G., Melillo R., Melillo T. Prefrontal Functional Connectivities in Autism Spectrum Disorders: A Connectopathic Disorder Affecting Movement, Interoception, and Cognition. Brain Research Bulletin, 2023, vol. 198, pp. 65–76. DOI: 10.1016/j.brainresbull.2023.04.004
24. Li F., Bai M., Xu J. et al. Long-Term Exercise Alters the Profiles of Circulating Micro-RNAs in the Plasma of Young Women. Frontiers in Physiology, 2020, vol. 11, art. 372. DOI: 10.3389/fphys. 2020.00372
25. Ling, C., Rönn, T. Epigenetic Adaptation to Regular Exercise in Humans. Drug Discovery Today, 2014, vol. 19 (7), pp. 1015–1018. DOI: 10.1016/j.drudis.2014.03.006
26. Lu B., Nagappan G., Lu Y. BDNF and Synaptic Plasticity, Cognitive Function, and Dysfunction. Handbook of Experimental Pharmacology, 2014, vol. 220, pp. 223–250. DOI: 10.1007/978-3-642-45106-5_9
27. Lucchina L., Depino A.M. et al. Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism. Autism Research: Official Journal of the International Society for Autism Research, 2014, vol. 7 (2), pp. 273–289. DOI: 10.1002/aur.1338
28. Ludyga S., Pühse U., Gerber M. et al. How Children with Neurodevelopmental Disorders can Benefit from the Neurocognitive Effects of Exercise. Neuroscience and Biobehavioral Rreviews, 2021, vol. 127, pp. 514–519. DOI: 10.1016/j.neubiorev.2021.04.039
29. Mallick R., Duttaroy A.K. Epigenetic Modification Impacting Brain Functions: Effects of Physical Activity, Micronutrients, Caffeine, Toxins, and Addictive Substances. Neurochemistry International, 2023, vol. 171, art. 105627. DOI: 10.1016/j.neuint.2023.105627
30. Martinez F.O., Helming L., Gordon S. Alternative Activation of Macrophages: an Immu-nologic Functional Perspective. Annual Review of Immunology, 2009, vol. 27, pp. 451–483. DOI: 10.1146/annurev.immunol.021908.132532
31. Mendes-Silva A.P., Pereira K.S., Tolentino-Araujo G.T. et al. Shared Biologic Pathways between Alzheimer Disease and Major Depression: A Systematic Review of MicroRNA Expression Studies. The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry, 2016, vol. 24 (10), pp. 903–912. DOI: 10.1016/j.jagp.2016.07.017
32. Mojtahedi S., Kordi M., Soleimani M. Effect of Different Intensities of Short Term Aerobic Exercise on Expression of miR-124 in the Hippocampus of Adult Male Rats. Zahedan Journal of Research in Medical Sciences, 2012, vol. 14.
33. Mor M., Nardone S., Sams D.S. et al. Hypomethylation of miR-142 Promoter and Upregulation of MicroRNAs that Target the Oxytocin Receptor Gene in the Autism Prefrontal Cortex. Molecular Autism, 2015, vol. 6, art. 46. DOI: 10.1186/s13229-015-0040-1
34. Mouat J.S., LaSalle J.M. The Promise of DNA Methylation in Understanding Multigenerational Factors in Autism Spectrum Disorders. Frontiers in Genetics, 2022, vol. 13, art. 831221. DOI: 10.3389/fgene.2022.831221
35. Nguyen L.S., Lepleux M., Makhlouf M. et al. Profiling Olfactory Stem Cells from Living Patients Identifies miRNAs Relevant for Autism Pathophysiology. Molecular Autism, 2016, vol. 7, art. 1. DOI: 10.1186/s13229-015-0064-6
36. Nguyen L.S., Fregeac J., Bole-Feysot C. et al. Role of miR-146a in Neural Stem Cell Differentiation and Neural Lineage Determination: Relevance for Neurodevelopmental Disorders. Molecular Autism, 2018, vol. 9, art. 38. DOI: 10.1186/s13229-018-0219-3
37. Olde Loohuis N.F., Kole K., Glennon J.C. et al. Elevated MicroRNA-181c and Mi-croRNA-30d Levels in the Enlarged Amygdala of the Valproic Acid Rat Model of Autism. Neurobiology of Disease, 2015, vol. 80, pp. 42–53. DOI: 10.1016/j.nbd.2015.05.006
38. Oriel K.N., George C.L., Peckus R. et al. The Effects of Aerobic Exercise on Academic Engagement in Young Children with Autism Spectrum Disorder. Pediatric Physical Therapy: the Official Publication of the Section on Pediatrics of the American Physical Therapy Association, 2011, vol. 23 (2), pp. 187–193. DOI: 10.1097/PEP.0b013e318218f149
39. Pitetti K.H., Rendoff A.D., Grover T. et al. The Efficacy of a 9-month Treadmill Walking Program on the Exercise Capacity and Weight Reduction for Adolescents with Severe Autism. Journal of Autism and Developmental Disorders, 2007, vol. 37 (6), pp. 997–1006. DOI: 10.1007/s10803-006-0238-3
40. Polakovičová M., Musil P., Laczo E., Hamar D. et al. Circulating MicroRNAs as Potential Biomarkers of Exercise Response. International Journal of Molecular Sciences, 2016, vol. 17 (10), art. 1553. DOI: 10.3390/ijms17101553
41. Ranieri A., Mennitti C., Falcone N. Positive Effects of Physical Activity in Autism Spectrum Disorder: how Influences Behavior, Metabolic Disorder and Gut Microbiota. Frontiers in Psychiatry, 2023, vol. 14, art. 1238797. DOI: 10.3389/fpsyt.2023.1238797
42. Rose S., Melnyk S., Pavliv O. et al. Evidence of Oxidative Damage and Inflammation Associated with Low Glutathione Redox Status in the Autism Brain. Translational Psychiatry, 2012, vol. 2 (7), art. e134. DOI: 10.1038/tp.2012.61
43. San-Millán I. The Key Role of Mitochondrial Function in Health and Disease. Antioxidants (Basel, Switzerland), 2023, vol. 12 (4), art. 782. DOI: 10.3390/antiox12040782
44. Sánchez-Mora C., Soler Artigas M., Garcia-Martínez I. et al. Epigenetic Signature for Attention-deficit/hyperactivity Disorder: Identification of miR-26b-5p, miR-185-5p, and miR-191-5p as
Potential Biomarkers in Peripheral Blood Mononuclear Cells. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 2019, vol. 44 (5), pp. 890–897. DOI: 10.1038/s41386-018-0297-0
45. Schenk A., Koliamitra C., Bauer C.J. Impact of Acute Aerobic Exercise on Genome-Wide DNA-Methylation in Natural Killer Cells-A Pilot Study. Genes, 2019, vol. 10 (5), art. 380. DOI: 10.3390/genes10050380
46. Schmitz Olin S., McFadden B.A., Golem D.L. et al. The Effects of Exercise Dose on Stereotypical Behavior in Children with Autism. Medicine and Science in Sports and Exercise, 2017, vol. 49 (5), pp. 983–990. DOI: 10.1249/MSS.0000000000001197
47. Shi P., Zhang Z., Feng X. Effect of Physical Exercise in Real-world Settings on Executive Function of Atypical Children: A Systematic Review and Meta-analysis. Child: Care, Health and Development, 2024, vol. 50 (1), art. e13182. DOI: 10.1111/cch.13182
48. Talebizadeh Z., Butler M.G., Theodoro M.F. Feasibility and Relevance of Examining Lymphoblastoid Cell Lines to Study Role of MicroRNAs in Autism. Autism Research: Official Journal of the International Society for Autism Research, 2008, vol. 1 (4), pp. 240–250. DOI: 10.1002/aur.33
49. Taylor D.F., Bishop D.J. Transcription Factor Movement and Exercise-Induced Mitochondrial Biogenesis in Human Skeletal Muscle: Current Knowledge and Future Perspectives. International Journal of Molecular Sciences, 2022, vol. 23 (3), art. 1517. DOI: 10.3390/ijms23031517
50. Toscano C.V.A., Barros L., Lima A.B. et al. Neuroinflammation in Autism Spectrum Disorders: Exercise as a “Pharmacological” Tool. Neuroscience and Biobehavioral Reviews, 2021, vol. 129, pp. 63–74. DOI: 10.1016/j.neubiorev.2021.07.023
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
52. Tse C.Y.A., Lee H.P., Chan K.S.K. et al. Examining the Impact of Physical Activity on Sleep Quality and Executive Functions in Children with Autism Spectrum Disorder: A Randomized Controlled Trial. Autism: the International Journal of Research and Practice, 2019, vol. 23 (7), pp. 1699–1710. DOI: 10.1177/1362361318823910
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
60. Zadehbagheri F., Hosseini E., Bagheri-Hosseinabadi Z. et al. Profiling of miRNAs in Serum of Children with Attention-deficit Hyperactivity Disorder Shows Significant Alterations. Journal of Psychiatric Research, 2019, vol. 109, pp. 185–192. DOI: 10.1016/j.jpsychires.2018.12.013
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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Опубликован
2024-12-26
Как цитировать
Протченко, А., & Ненашева, А. (2024). ИССЛЕДОВАНИЕ ВЛИЯНИЯ ФИЗИЧЕСКОЙ АКТИВНОСТИ НА ЭКСПРЕССИЮ ГЕНОВ ПРИ РАССТРОЙСТВАХ АУТИСТИЧЕСКОГО СПЕКТРА (ОБЗОР ЛИТЕРАТУРЫ). Человек. Спорт. Медицина, 24(3), 42-52. https://doi.org/10.14529/hsm240305
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Физиология
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