РОЛЬ МИОКИНОВ В УЛУЧШЕНИИ КОГНИТИВНЫХ ФУНКЦИЙ

За последние пару десятилетий стало очевидным, что скелетные мышцы работают как эндокринный орган, который может вырабатывать и секретировать миокины, оказывающие свое действие эндокринным, паракринным или аутокринным образом. Современные исследования показывают, что физические усилия индуцируют синтез молекул, участвующих в передаче сигналов между клетками скелетной мускулатуры и другими органами, в частности головным мозгом, жировой тканью, органами желудочно-кишечного тракта, а также клетками кожи и сосудов. В данном обзоре рассмотрены миокины, которые обусловливают связь с мозгом, нейропротекцию в ответ на физические нагрузки и связанные с ними процессы. В отличие от защитных миокинов, индуцируемых физической нагрузкой, и связанных с ними сигнальных путей, гиподинамия и истощение мышц могут нарушать экспрессию и секрецию миокинов и, в свою очередь, нарушать функцию центральной нервной системы. Предполагается, что адаптация передачи сигналов от мышц к головному мозгу путем модуляции миокинов поможет бороться с возрастной нейродегенерацией и заболеваниями мозга, на которые влияют системные сигналы.

1. Rai M., Demontis F. Systemic Nutrient and Stress Signaling via Myokines and Myometabolites. Annu Rev Physiol. 2016. 78:85-107. DOI: 10.1146/annurev-physiol-021115-105305.

2. Gomarasca M., Banfi G., Lombardi G. Myokines: The endocrine coupling of skeletal muscle and bone. Adv Clin Chem. 2020. 94:155-218. DOI: 10.1016/bs.acc.2019.07.010.

3. Rai M., Demontis F. Muscle-to-Brain Signaling Via Myokines and Myometabolites. Brain Plast. 2022. Oct 21. 8(1):43-63. DOI: 10.3233/BPL-210133.

4. Isaac A.R., Lima-Filho R.A.S., Lourenco M.V. How does the skeletal muscle communicate with the brain in healthanddisease?Neuropharmacology.2021.Oct1.197:108744.DOI:10.1016/j.neuropharm.2021.108744.

5. Qi J.Y., Yang L.K., Wang X.S. et al. Mechanism of CNS regulation by irisin, a multifunctional protein. Brain Res Bull. 2022. Oct 1. 188:11-20. DOI: 10.1016/j.brainresbull.2022.07.007.

6. Langan S.P., Grosicki G.J. Exercise Is Medicine…and the Dose Matters. Front Physiol. 2021. May 12. 12:660818. DOI: 10.3389/fphys.2021.660818.

7. Atakan M.M., Li Y., Koşar Ş.N., Turnagöl H.H., Yan X. Evidence-Based Effects of High-Intensity Interval Training on Exercise Capacity and Health: A Review with Historical Perspective. Int J Environ Res Public Health. 2021. Jul 5. 18(13):7201. DOI: 10.3390/ijerph18137201.

8. Augusto-Oliveira M., Arrifano G.P., Leal-Nazaré C.G. et al. Exercise Reshapes the Brain: Molecular, Cellular, and Structural Changes Associated with Cognitive Improvements. Mol Neurobiol. 2023. Dec. 60(12):6950-6974. DOI: 10.1007/s12035-023-03492-8.

9. Mela V., Mota B.C., Milner M. et al. Exercise-induced re-programming of age-related metabolic changes in microglia is accompanied by a reduction in senescent cells. Brain Behav Immun. 2020. Jul. 87:413-428. DOI: 10.1016/j.bbi.2020.01.012.

10. Pahlavani H.A. Exercise therapy to prevent and treat Alzheimer’s disease. Front Aging Neurosci. 2023. Aug. 4.15:1243869. DOI: 10.3389/fnagi.2023.1243869.

11. Pataky M.W., Nair K.S. Too much of a good thing: Excess exercise can harm mitochondria. Cell Metab. 2021. May 4. 33(5):847-848. DOI: 10.1016/j.cmet.2021.04.008.

12. Rosa E.F., Takahashi S., Aboulafia J., Nouailhetas V.L., Oliveira M.G. Oxidative stress induced by intense and exhaustive exercise impairs murine cognitive function. J Neurophysiol. 2007. Sep. 98(3):1820-6. DOI: 10.1152/jn.01158.2006.

13. Li Y., Tian X., Luo J. et al. Molecular mechanisms of aging and anti-aging strategies. Cell Commun Signal. 2024. May 24. 22(1):285. DOI: 10.1186/s12964-024-01663-1.

14. Driss L.B., Lian J., Walker R.G. et al. GDF11 and aging biology - controversies resolved and pending. J Cardiovasc Aging. 2023. Oct. 3(4):42. DOI: 10.20517/jca.2023.23.

15. Sa-Nguanmoo P., Tanajak P., Kerdphoo S. et al. FGF21 improves cognition by restored synaptic plasticity, dendritic spine density, brain mitochondrial function and cell apoptosis in obese-insulin resistant male rats. Horm Behav. 2016. Sep. 85:86-95. DOI: 10.1016/j.yhbeh.2016.08.006.

16. Rai M., Demontis F. Muscle-to-Brain Signaling Via Myokines and Myometabolites. Brain Plast. 2022. Oct 21. 8(1):43-63. DOI: 10.3233/BPL-210133.

17. Mancinelli R., Checcaglini F., Coscia F. et al. Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging. Int J Mol Sci. 2021. Aug 7. 22(16):8520. DOI: 10.3390/ijms22168520.

18. Stansberry W.M., Pierchala B.A. Neurotrophic factors in the physiology of motor neurons and their role in the pathobiology and therapeutic approach to amyotrophic lateral sclerosis. Front Mol Neurosci. 2023. Aug 24. 16:1238453. DOI: 10.3389/fnmol.2023.1238453.

19. Numakawa T., Odaka H., Adachi N. Actions of Brain-Derived Neurotrophin Factor in the Neurogenesis and Neuronal Function, and Its Involvement in the Pathophysiology of Brain Diseases. Int J Mol Sci. 2018. Nov 19. 19(11):3650. DOI: 10.3390/ijms19113650.

20. Arévalo J.C., Deogracias R. Mechanisms Controlling the Expression and Secretion of BDNF. Biomolecules. 2023. May 2. 13(5):789. DOI: 10.3390/biom13050789.

21. Merighi A. Brain-Derived Neurotrophic Factor, Nociception, and Pain. Biomolecules. 2024. Apr 30. 14(5):539. DOI: 10.3390/biom14050539.

22. Leger C., Quirié A., Méloux A. et al. Impact of Exercise Intensity on Cerebral BDNF Levels: Role of FNDC5/Irisin. Int J Mol Sci. 2024. Jan 19. 25(2):1213. DOI: 10.3390/ijms25021213.

23. Colucci-D'Amato L., Speranza L., Volpicelli F. Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. Int J Mol Sci. 2020. Oct 21. 21(20):7777. DOI: 10.3390/ijms21207777.

24. Begni V., Riva M.A., Cattaneo A. Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions. Clin Sci (Lond). 2017. Jan 1. 131(2):123-138. DOI: 10.1042/CS20160009.

25. Loprinzi P.D., Day S., Deming R. Acute Exercise Intensity and Memory Function: Evaluation of the Transient Hypofrontality Hypothesis. Medicina (Kaunas). 2019. Aug 7. 55(8):445. DOI: 10.3390/medicina55080445.

26. von Bohlen Und Halbach O. Neurotrophic Factors and Dendritic Spines. Adv Neurobiol. 2023. 34:223- 254. DOI: 10.1007/978-3-031-36159-3_5.

27. de Assis G.G., de Almondes K.M. Exercise-dependent BDNF as a Modulatory Factor for the Executive Processing of Individuals in Course of Cognitive Decline. A Systematic Review. Front Psychol. 2017. Apr 19. 8:584. DOI: 10.3389/fpsyg.2017.00584.

28. Rosenbaum S., Lagopoulos J., Curtis J. et al. Aerobic exercise intervention in young people with schizophrenia spectrum disorders; improved fitness with no change in hippocampal volume. Psychiatry Res. 2015. May 30. 232(2):200-1. DOI: 10.1016/j.pscychresns.2015.02.004.

29. Moon H.Y., Becke A., Berron D. et al. Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function. Cell Metab. 2016. Aug 9. 24(2):332-40. DOI: 10.1016/j.cmet.2016.05.025.

30. Boström P., Wu J., Jedrychowski M.P. et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012. Jan 1. 481(7382):463-8. DOI: 10.1038/nature10777.

31. Siteneski A., Cunha M.P., Lieberknecht V. et al. Central irisin administration affords antidepressant-like effect and modulates neuroplasticity-related genes in the hippocampus and prefrontal cortex of mice. Prog Neuropsychopharmacol Biol Psychiatry. 2018. Jun 8. 84(Pt A):294-303. DOI: 10.1016/j.pnpbp.2018.03.004.

32. Xu M., Zhu J., Liu X.D., Luo M.Y., Xu N.J. Roles of physical exercise in neurodegeneration: reversal of epigenetic clock. Transl Neurodegener. 2021. Aug 13. 10(1):30. DOI: 10.1186/s40035-021-00254-1.

33. Pignataro P., Dicarlo M., Zerlotin R. et al. FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective. Int J Mol Sci. 2021. Feb 5. 22(4):1605. DOI: 10.3390/ijms22041605.

34. Dong Y., Yuan H., Ma G., Cao H. Bone-muscle crosstalk under physiological and pathological conditions. Cell Mol Life Sci. 2024. Jul 27. 81(1):310. DOI: 10.1007/s00018-024-05331-y.

35. Zhang J., Tian Z., Qin C., Momeni M.R. The effects of exercise on epigenetic modifications: focus on DNA methylation, histone modifications and non-coding RNAs. Hum Cell. 2024. Jul. 37(4):887-903. DOI: 10.1007/s13577-024-01057-y.

36. Walzik D., Wences Chirino T.Y., Zimmer P., Joisten N. Molecular insights of exercise therapy in disease prevention and treatment. Signal Transduct Target Ther. 2024. May 29. 9(1):138. DOI: 10.1038/s41392-024-01841-0.

37. Marinus N., Hansen D., Feys P. et al. The Impact of Different Types of Exercise Training on Peripheral Blood Brain-Derived Neurotrophic Factor Concentrations in Older Adults: A Meta-Analysis. Sports Med. 2019. Oct. 49(10):1529-1546. DOI: 10.1007/s40279-019-01148-z.

38. Delezie J., Weihrauch M., Maier G. et al. BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle. Proc Natl Acad Sci U S A. 2019. Aug 6. 116(32):16111-16120. DOI: 10.1073/pnas.1900544116.

39. Cefis M., Chaney R., Wirtz J. et al. Molecular mechanisms underlying physical exercise-induced brain BDNF overproduction. Front Mol Neurosci. 2023. Oct 5. 16:1275924. DOI: 10.3389/fnmol.2023.1275924.