EXERCISE AND NEUROGENESIS

Year 2021, , 264 - 268, 25.04.2021

Mehmet Ünal

https://doi.org/10.26650/IUITFD.2020.0066

Abstract

Neurogenesis is a biological process characterized by the formation of new neurons. During embryogenesis, neural stem cells multiply, migrate, and differentiate into mature neurons that will eventually form the central nervous system. After proliferation, differentiation, and displacement, it has been proven that, during exercise, new neurons in the dentate gyrus settle in the neural circuits of the hippocampus and brain areas that are important for memory consolidation and learning. During and after exercise, the triggering factor for exercise-induced neurogenesis is a molecule called brain-derived neurotrophic factor, also known as BDNF in recent publications. Being a member of the neurotrophin family, BDNF is vital for many functions involved in neurogenesis, including proliferation, differentiation, maturation, and survival. Besides BDNF, signal pathways molecules, such as insulin-like growth factor-1, fibroblast growth factor 2, and vascular endothelial growth factor, have also proven to be effective in neuroplasticity and hippocampal neurogenesis. During physical activities, the most affected brain region is the hippocampus. Aerobic exercises have been found to significantly increase the size and function of the human hippocampus, especially when performed with moderate exercise; it is important to ensure that the exercise is not stressful. Stress suppresses neurogenesis by increasing the release of glucocorticoids in the hypothalamic–pituitary–adrenal axis and thus prevents the formation of new neurons. If voluntary exercise exceeds a certain threshold and become exhaustion, neurogenesis is prevented via the same mechanism. Therefore, it is important that exercise is done according to each person’s ability and should not cause exhaustion.

Keywords

Neurogenesis, exercise, brain ınduced neurotrophic factor (BDNF Protein)

EGZERSİZ VE NÖROGENEZ

Abstract

Nörogenez, yeni nöronların oluştuğu biyolojik bir süreçtir. Nöral kök hücreler, embriyogenez sırasında, merkezi sinir sistemini oluşturacak olgun nöronlar halinde çoğalır, göç eder ve farklılaşır. Proliferasyonun, farklılaşmanın ve yer değiştirmenin ardından, egzersiz ile dentat girusda yeni doğan nöronların hipokampusun sinirsel devrelerine ve bellek konsolidasyonu ve öğrenme için önemli olan beyin bölgelerine yerleştiği kanıtlanmıştır. Egzersiz esnasında ve sonrasında “Egzersiz kaynaklı nörogenezi tetikleyen faktörün”, son yayınlarda beyin kaynaklı nörotrofik faktör (brain-derived neurotrophic factor-BDNF) adlı bir molekül olduğunun ön planda tutulduğu görülmektedir. Nörotrofin ailesinin bir üyesi olan BDNF, proliferasyon, farklılaşma, olgunlaşma ve hayatta kalma dahil olmak üzere nörogenezden sorumlu birçok fonksiyon için hayati öneme sahiptir. BDNF’nin yanı sıra nöroplastisite ve hipokampal nörogenezde İnsülin Benzeri Büyüme Faktörü-1 (IGF-1), Fibroblast Büyüme Faktörü-2 (FGF-2), Vasculer- Endotelyal Büyüme Faktörü (VEGF) gibi sinyal yolaklarının da etkili olduğu gösterilmiştir. Fiziksel aktivitelerde en fazla etkilenen beyin bölgesi hipokampus bölgesidir. Aerobik egzersizlerin, özellikle de aşırıya kaçmadan yapıldığında, insanların hipokampus boyutunda ve fonksiyonlarında anlamlı artışlara neden olduğu tespit edilmiştir. Egzersizin bir stres haline dönüştürülmemesi önemlidir. Stres Hipotalamo-hipofiz-adrenal korteks ekseninde glikokortikoid salınımını artırarak nörogenezi baskılamakta, yeni nöron oluşumuna engel olmaktadır. İstemli yapılan egzersizler bile belirli bir seviyenin üzerinde olursa, tüketici hale geldiğinde yine aynı mekanizma ile nörogenezi engellemektedir. Bu nedenle egzersizin kişiye özel olması ve tükenmeye neden olacak kadar olmaması önemlidir.

Keywords

Nörogenez, egzersiz, beyin kaynaklı nörotrofik faktör

References

• 1. Liu PZ, Nusslock R. Exercise and hippocampal neurogenesis: a dogma re-examined and lessons learned. Neural Regen Res 2018;13(8):1354-5. [CrossRef]
• 2. Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab 2013;18(5):649-59. [CrossRef]
• 3. Voss MW, Heo S, Prakash RS, Erickson KI, Alves H, Chaddock L, et al. The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: Results of a one-year exercise intervention. Hum Brain Mapp 2013;34(11):2972-85. [CrossRef]
• 4. Ünal M. Alzheimer Hastalarında Egzersiz Uygulamaları. In: Ünal M, editor. Alzheimer’a Dair Her Şey. İstanbul: İstanbul Tıp Kitapevi; 2018.p.139-70.
• 5. Ünal M, Erdem S, Deniz G. The Effects Of Chronic Aerobic And Anaerobic Exercises On Lymphocyte Subgroups. Acta Physiol Hung 2005;92(2):163-71. [CrossRef]
• 6. Ma CL, Ma XT, Wang JJ, Liu H, Chen YF, Yang Y. Physical exercise induces hippocampal neurogenesis and prevents cognitive decline. Behav Brain Res 2017;317:332- 9. [CrossRef] 7. Altman J. Are new neurons formed in the brains of adult mammals? Science 1962;135(3509):1127-8. [CrossRef]
• 8. Gould E, Tanapat P, McEwen BS, Flügge G, Fuchs E. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci U S A 1998; 95(6):3168-71. [CrossRef]
• 9. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, et al. Neurogenesis in the adult human hippocampus. Nat Med 1998;4(11):1313-7. [CrossRef]
• 10. Kempermann G, Kuhn HG, Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature 1997;386(6624):493-5. [CrossRef]
• 11. Van Praag H, Kempermann G, Gage FH.Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999;2(3):266-70. [CrossRef]
• 12. Choi SH, Bylykbashi E, Chatila ZK, Lee SW, Pulli B, Clemenson GD, et al. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science 2018;361(6406):eaan8821. [CrossRef]
• 13. Altman J, Das GD. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 1965;124(3):319-35. [CrossRef]
• 14. Kempermann G. Activity dependency and aging in the regulation of adult neurogenesis. Cold Spring Harb Perspect Biol 2015;7(11):a018929. [CrossRef]
• 15. O’Leary JD, Hoban AE, Murphy A, O’Leary OF, Cryan JF, Nolan YM. Differential effects of adolescent and adult-initiated exercise on cognition and hippocampal neurogenesis. Hippocampus 2019;29(4):352- 65. [CrossRef]
• 16. Woost L, Bazin PL, Taubert M, Trampel R,Tardif CL,Garthe A, at al. Physical Exercise and Spatial Training: A Longitudinal Study of Effects on Cognition, Growth Factors, and Hippocampal Plasticity. Sci Rep 2018;8(1):4239. [CrossRef]
• 17. Ernst A, Frisen J. Adult neurogenesis in humanscommon and unique traits in mammals. PLoS Biol 2015;13(1):e1002045. [CrossRef]
• 18. Liu PZ, Nusslock R. Exercise-mediated neurogenesis in the hippocampus via BDNF. Front Neurosci 2018;12:52. [CrossRef]
• 19. Tharmaratnam T,Tabobondung T, Tabobondung T, Doherty S. Synergistic effects of brain-derived neurotrophic factor (BDNF) and exercise intensity on memory in the adolescent brain: a commentary. Environ Health Prev Med 2018;23(1):12. [CrossRef]
• 20. Jeon YK, Ha CH. The effect of exercise intensity on brain derived neurotrophic factor and memory in adolescents. Environ Health Prev Med 2017;22(1):27. [CrossRef]
• 21. Baptista P, Andrade JP. Adult Hippocampal Neurogenesis: Regulation and Possible Functional and Clinical Correlates. Front Neuroanat 2018;12:44. [CrossRef]
• 22. Chapman SB, Aslan S, Spence JS, Keebler MW, DeFina LF, Didehbani N, et al. Distinct brain and behavioral benefits from cognitive vs. physical training: a randomized trial in aging adults. Front Hum Neurosci 2016;10:338. [CrossRef]
• 23. Heath M, Weiler J, Gregory MA, Gill DP, Petrella RJ. A six-month cognitive-motor and aerobic exercise program improves executive function in persons with an objective cognitive impairment: a pilot investigation using the antisaccade task. J Alzheimers Dis 2016;54(3):923-31.v [CrossRef]
• 24. Sorrells SF, Paredes MF, Cebrian-Silla A, Sandoval K, Qi D, Kelley KW, et al. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 2018;555(7696):377-81. [CrossRef]
• 25. Gheorghe A, Qiu W, Galea LAM. Hormonal Regulation of Hippocampal Neurogenesis: Implications for Depression and Exercise. Curr Top Behav Neurosci 2019;43:379-421. [CrossRef]
• 26. Davis CL, Cooper S. Fitness, fatness, cognition, behavior, and academic achievement among overweight children: do cross-sectional associations correspond to exercise trial outcomes? Prev Med 2011;52:65-9. [CrossRef]
• 27. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A 2011;108(7):3017-22. [CrossRef]
• 28. Ehninger D, Kempermann G. Regional effects of wheel running and environmental enrichment on cell genesis and microglia proliferation in the adult murine neocortex. Cereb Cortex 2003;13(8):845-51. [CrossRef] 2
• 9. Nurten A. Alheimer Hastalığı ve Nörofizyolojik Değişiklikler. In: Ünal M, editor. Alzheimer’a Dair Her Şey. İstanbul: İstanbul Tıp Kitapevi; 2018;77-87.
• 30. Laurin D, Verreault R, Lindsay J, MacPherson K, Rockwood K. Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol 2001;58(3):498- 504. [CrossRef]
• 31. Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 2012;64(2):238-58. [CrossRef]
• 32. Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, et al. Dynamics of hippocampal neurogenesis in adult humans. Cell 2013;153(6):1219-27. [CrossRef]
• 33. Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, et al. An in vivo correlate of exerciseinduced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A 2007;104(13):5638-43. [CrossRef]
• 34. Kempermann G. New neurons for ‘survival of the fittest’. Nat Rev Neurosci 2012;13(10):727-36. [CrossRef]
• 35. Xu X, Fu Z, Le W. Exercise and Parkinson’s disease. Int Rev Neurobiol 2019;147:45-74. [CrossRef]
• 36. Meeusen R. Exercise, nutrition and the brain. Sports Med 2014;44:47-56. [CrossRef]
• 37. Voss MW, Heo S, Prakash RS, Erickson KI, Alves H, Chaddock L, et al. The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: Results of a one-year exercise intervention. Hum Brain Mapp 2013;34(11):2972-85. [CrossRef]
• 38. Cardoso A, Marrana F, Andrade JP. Caloric restriction in young rats disturbs hippocampal neurogenesis and spatial learning. Neurobiol Learn Mem 2016;133:214-24. [CrossRef]
• 39. Leuner B, Glasper ER, Gould E. Sexual experience promotes adult neurogenesis in the hippocampus despite an initial elevation in stress hormones. PLoS One 2010;5(7):e11597. [CrossRef]