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트레드밀 운동이 청소년기 흰쥐의 기억력과 해마 신경세포생성, BDNF, TrkB, 그리고 전뇌 콜린 세포에 미치는 영향

Effects of Treadmill Exercise on Memory, Hippocampal Cell Proliferation, BDNF, TrkB, and Forebrain Cholinergic Cells in Adolescent Rats

  • 이희혁 (한남대학교 생활체육학과)
  • Lee, Hee-Hyuk (Department of Sports Science, Hannam University)
  • 발행 : 2009.03.31

초록

본 연구는 청소년기 흰쥐를 대상으로 4주간의 저강도 트레드밀 운동이 기억력과 해마 신경세포생성, BDNF, Trkb, 중격 콜린세포에 미치는 효과를 조사하기 위하여 수행되었다. 먼저 운동이 기억력에 미치는 효과를 step-through avoidance에서 검사한 결과 운동을 실시했던 흰쥐의 retention latency가 대조군에 비해 유의하게 증가되어 기억력 향상을 나타내었다. 이후 기억력 향상기전으로 해마에서 신경세포증식과 BDNF 및 TrkB 단백질 발현을 정량화 한 결과에서도 운동군의 신경세포 생성율과 BDNF와 TrkB 단백질 발현 모두 대조군에 비해 유의하게 증가된 것으로 나타났다. 게다가 운동을 통한 전뇌 콜린세포 수의 증가가 해마 신경세포생성과 BDNF 발현 증가에 기여하는 것으로 나타났다. 이러한 결과는 청소년기 운동이 기억력 향상에 도움이 될 수 있음을 보여주는 것이다.

This study investigated the effects of treadmill exercise on memory ability, cell proliferation, BDNF, and TrkB in the hippocampus and forebrain cholinergic cells in adolescent rats. Male Sprague-Dawley rats (4 weeks old) were randomly assigned to the following two groups: the sedentary group (n=10) and the exercise group (n=10). Rats in the exercise group were forced to run on a treadmill for 30 min, five times per week for 4 weeks. The latency of the step-through avoidance task was used in order to evaluate memory ability. Hippocampal brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) expression were assessed by Western blotting. Hippocampal cell proliferation and forebrain cholinergic cells were assessed by immunohistochemistry. The present study showed that treadmill running during the adolescent period significantly improved memory capability, increased hippocampal cell proliferation, up-regulated hippocampal BDNF and TrkB expression, and enhanced the number of forebrain cholinergic cells. These results suggest that regular exercise during the adolescent period may enhance memory function.

키워드

참고문헌

  1. Achiron, A. and A. Kalron. 2008. Physical activity: positive impact on brain plasticity. Harefuah 147, 252-255
  2. Aguiar, A. S., A. E. Speck, R. D. Prediger, F. Kapczinski, and R. A. Pinho. 2008. Downhill training upregulates mice hippocampal and striatal brain-derived neurotrophic factor levels. J. Neural. Transm. 115, 1251-1255 https://doi.org/10.1007/s00702-008-0071-2
  3. Anderson, B. J., D. N. Rapp, D. H. Baek, D. P. McCloskey, P. S. Coburn-Litvak, and J. K. Robinson. 2000. Exercise influences spatial learning in the radial arm maze. Physiol. Behav. 70, 425-429 https://doi.org/10.1016/S0031-9384(00)00282-1
  4. Ang, E. T., G. S. Dawe, P. T. Wong, S. Moochhala, and Y. K. Ng. 2006. Alterations in spatial learning and memory after forced exercise. Brain Res. 1113, 186-193 https://doi.org/10.1016/j.brainres.2006.07.023
  5. Bekinschtein, P., M. Cammarota, C. Katche, L. Slipczuk, J. L. Rossato, A. Goldin, I. Izquierdo and J. H. Medina. 2008. BDNF is essential to promote persistence of long-term memory storage. Proc. Natl. Acad. Sci. 105, 2711-2716 https://doi.org/10.1073/pnas.0711863105
  6. Berchtold, N. C., G. Chinn, M. Chou, J. P. Kesslak, and C. W. Cotman. 2005. Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience 133, 853-861 https://doi.org/10.1016/j.neuroscience.2005.03.026
  7. Berchtold, N. C., J. P. Kesslak, and C. W. Cotman. 2002. Hippocampal brain-derived neurotrophic factor gene regulation by exercise and the medial septum. J. Neurosci. Res. 68, 511-521 https://doi.org/10.1002/jnr.10256
  8. Chan, J. P., J. Cordeira, G. A. Calderon, L. K. Iyer, and M. Rios. 2008. Depletion of central BDNF in mice impedes terminal differentiation of new granule neurons in the adult hippocampus. Mol. Cell Neurosci. 39, 372-383 https://doi.org/10.1016/j.mcn.2008.07.017
  9. Cooper-Kuhn, C. M., J. Winkler, and H. Kuhn. 2004. Decreased neurogenesis after cholinergic forebrain lesion in the adult rat. J. Neurosci. Res. 77, 155-165 https://doi.org/10.1002/jnr.20116
  10. Dayer, A. G., A. A. Ford, K. M. Cleaver, M. Yassaee, and H. A. Cameron. 2003. Short-term and long-term survival of new neurons in the rat dentate gyrus. J. Comp. Neurol. 460, 563-572 https://doi.org/10.1016/j.neulet.2003.12.123
  11. Donovan, M. H., M. Yamaguchi, and A. J. Eisch. 2008. Dynamic expression of TrkB receptor protein on proliferating and maturing cells in the adult mouse dentate gyrus. Hippocampus 18, 435-439 https://doi.org/10.1002/hipo.20410
  12. Eriksson, P. S., E. Perfilieva, T. Bjork-Eriksson, A. M. Alborn, C. Nordborg, D. A. Peterson, and F. H. Gage. 1998. Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313-1317 https://doi.org/10.1038/3305
  13. Ferencz, I., M. Kokaia, M. Keep, E. Elmér, M. Metsis, and Z. Kokaia. 1997. Effects of cholinergic denervation on seizure development and neurotrophin messenger RNA regulation in rapid hippocampal kindling. Neuroscience 80, 389-399 https://doi.org/10.1016/S0306-4522(97)00006-7
  14. French, S. J., T. Humby, C. H. Horner, M. V. Sofroniew, and M. Rattray. 1999. Hippocampal neurotrophin and trk receptor mRNA levels are altered by local administration of nicotine, carbachol and pilocarpine. Brain Res. Mol. Brain. Res. 67, 124-136 https://doi.org/10.1016/S0169-328X(99)00048-0
  15. Fujioka, T., A. Fujioka, and R. S. Duman. 2004. Activation of cAMP signaling facilitates the morphological maturation of newborn neurons in adult hippocampus. J. Neurosci. 24, 319-328 https://doi.org/10.1523/JNEUROSCI.1065.03.2004
  16. Gold, P. E. 2003. Acetylcholine modulation of neural systems involved in learning and memory. Neurobiol. Learn. Mem. 80, 194-210 https://doi.org/10.1016/j.nlm.2003.07.003
  17. Harrell, L. E., A. D. Peagler, and D. S. Parsons. 1987. Passive-avoidance learning after medial septal lesions: effect of experience and the peripheral sympathetic nervous system. Exp. Neurol. 97, 542-554 https://doi.org/10.1016/0014-4886(87)90112-9
  18. Hu, Y. and S. J. Russek. 2008. BDNF and the diseased nervous system: a delicate balance between adaptive and pathological processes of gene regulation. J. Neurochem. 105, 1-17 https://doi.org/10.1111/j.1471-4159.2008.05237.x
  19. Jeong, I. G., J. H. Yoon, and H. H. Lee. 2008. Effects of Exercise Pre-conditioning on Memory and Cell Proliferation in the Hippocampus of the Rats with Streptozotocin-induced Alzheimer's disease. Journal of Life Science 18. 631-638 https://doi.org/10.5352/JLS.2008.18.5.631
  20. Kaneko, N., H. Okano, and K. Sawamoto. 2006. Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulb. Genes Cells 11, 1145-1159 https://doi.org/10.1111/j.1365-2443.2006.01010.x
  21. Kim, Y. P., H. B. Kim, M. H. Jang, B. V. Lim, Y. J. Kim, H. Kim, and C. J. Kim. 2003. Magnitude- and time-dependence of the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats. Int. J. Sports Med. 24, 114-117 https://doi.org/10.1055/s-2003-38202
  22. Kotani, S., T. Yamauchi, T. Teramoto, and H. Ogura. 2006. Pharmacological evidence of cholinergic involvement in adult hippocampal neurogenesis in rats. Neuroscience 142, 505-514 https://doi.org/10.1016/j.neuroscience.2006.06.035
  23. Kronenberg, G., A. Bick-Sander, E. Bunk, C. Wolf, D. Ehninger, and G. Kempermann. 2006. Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol. Aging 27, 1505-1513 https://doi.org/10.1016/j.neurobiolaging.2005.09.016
  24. Laurin, D., R. Verreault, J. Lindsay, K. MacPherson, and K. Rockwood. 2001. Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch. Neurol. 58, 498-504 https://doi.org/10.1001/archneur.58.3.498
  25. Lawson, V. H. and B. H. Bland. 1993. The role of the septohippocampal pathway in the regulation of hippocampal field activity and behavior: analysis by the intraseptal microinfusion of carbachol, atropine, and procaine. Exp. Neurol. 120, 132-144 https://doi.org/10.1006/exnr.1993.1047
  26. Lee, J. L., B. J. Everitt, and K. L. Thomas. 2004. Independent cellular processes for hippocampal memory consolidation and reconsolidation. Science 304, 839-843 https://doi.org/10.1126/science.1095760
  27. Lee, H. H., J. H. Yoon, and S. H. Kim. 2007. Effects of Treadmill Exercise on Memory and Hippocampal BDNF Expression in Streptozotocin-induced Diabetic Rats. Journal of Life Science 17, 1461-1471
  28. Li, Y., B. W. Luikart, S. Birnbaum, J. Chen, C. H. Kwon, S. G. Kernie, R. Bassel-Duby, and L. F. Parada. 2008. TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59, 399-412 https://doi.org/10.1016/j.neuron.2008.06.023
  29. Lindefors, N., P. Ernfors, T. Falkenberg, and H. Persson. 1992. Septal cholinergic afferents regulate expression of brain-derived neurotrophic factor and betanerve growth factor mRNA in rat hippocampus. Exp. Brain Res. 88, 78-90 https://doi.org/10.1007/BF02259130
  30. Lou, S. J., J. Y. Liu, H. Chang, and P. J. Chen. 2008. Hippocampal neurogenesis and gene expression depend on exercise intensity in juvenile rats. Brain Res. 1210, 48-55 https://doi.org/10.1016/j.brainres.2008.02.080
  31. Ma, Q. 2008. Beneficial effects of moderate voluntary physical exercise and its biological mechanisms on brain health. Neurosci. Bull. 24, 265-270 https://doi.org/10.1007/s12264-008-0402-1
  32. Mattson, M. P., S. Maudsley, and B. Martin. 2004. BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci. 27, 589-594 https://doi.org/10.1016/j.tins.2004.08.001
  33. Mizuno, M., K. Yamada, A. Olariu, H. Nawa, and T. Nabeshima. 2000. Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. J. Neurosci. 20, 7116-7121
  34. Morcuende, S., C. A. Gadd, M. Peters, A. Moss, E. A. Harris, A. Sheasby, A. S. Fisher, C. De Felipe, P. W. N. M. Rupniak, K. P. Giese, and S. P. Hunt. 2003. Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice. Eur. J. Neurosci. 18, 1828-1836 https://doi.org/10.1046/j.1460-9568.2003.02911.x
  35. Murray, K. D., C. M. Gall, E. G. Jones, and P. J. Isackson. 1994. Differential regulation of brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase messenger RNA expression in Alzheimer's disease. Neuroscience 60, 37-48 https://doi.org/10.1016/0306-4522(94)90202-X
  36. Nilsson, O. G., P. Kalen, E. Rosengren, and A. Bjorklund. 1990. Acetylcholine release in the rat hippocampus as studied by microdialysis is dependent on axonal impulse flow and increases during behavioural activation. Neuroscience 36, 325-338 https://doi.org/10.1016/0306-4522(90)90429-8
  37. Pinnock, S. B. and J. Herbert. 2008. Brain-derived neurotropic factor and neurogenesis in the adult rat dentate gyrus: interactions with corticosterone. Eur. J. Neurosci. 27, 2493-2500 https://doi.org/10.1111/j.1460-9568.2008.06250.x
  38. Ploughman, M., S. Granter-Button, G. Chernenko, Z. Attwood, B. A. Tucker, K. M. Mearow, and D. Corbett. 2007. Exercise intensity influences the temporal profile of growth factors involved in neuronal plasticity following focal ischemia. Brain Res. 1150, 207-216 https://doi.org/10.1016/j.brainres.2007.02.065
  39. Ramirez-Amaya, V., D. F. Marrone, F. H. Gage, P. F. Worley, and C. A. Barnes. 2006. Integration of new neurons into functional neural networks. J. Neurosci. 26, 12237-12241 https://doi.org/10.1523/JNEUROSCI.2195-06.2006
  40. Rice, D. and B. J. Stan. 2000. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ. Health Perspect. 108, 511-533 https://doi.org/10.2307/3454543
  41. Rossi, C., A. Angelucci, L. Costantin, C. Braschi, M. Mazzantini, F. Babbini, M. E. Fabbri, L. Tessarollo, L. Maffei, N. Berardi, and M. Caleo. 2006. Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur. J. Neurosci. 24, 1850-1856 https://doi.org/10.1111/j.1460-9568.2006.05059.x
  42. Sairanen, M., G. Lucas, P. Ernfors, M. Castr$\acute{e}$n, and E. Castr$\acute{e}$n. 2005. Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J. Neurosci. 25, 1089-1094 https://doi.org/10.1523/JNEUROSCI.3741-04.2005
  43. Shors, T. J., G. Miesegaes, A. Beylin, M. Zhao, and T. G. E. Rydel. 2001. Neurogenesis in the adult is involved in the formation of trace memories. Nature 410, 372-376 https://doi.org/10.1038/35066584
  44. Soya, H., T. Nakamura, C. C. Deocaris, A. Kimpara, M. Iimura, T. Fujikawa, H. Chang, B. S. McEwen, and T. Nishijima. 2007. BDNF induction with mild exercise in the rat hippocampus. Biochem. Biophys. Res. Commun. 358, 961-967 https://doi.org/10.1016/j.bbrc.2007.04.173
  45. Spear, L. P. 2000. The adolescent brain and age-related behavioral manifestations. Neurosci. Biobehav. Rev. 24, 417-463 https://doi.org/10.1016/S0149-7634(00)00014-2
  46. Trejo, J. L., E. Carro, and I. Torres-Aleman. 2001. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J. Neurosci. 21, 1628-1634
  47. Uysal, N., K. Tugyan, B. M. Kayatekin, O. Acikgoz, H. A. Bagriyanik, S. Gonenc, D. Ozdemir, I. Aksu, A. Topcu, and I. Semin. 2005. The effects of regular aerobic exercise in adolescent period on hippocampal neuron density, apoptosis and spatial memory. Neurosci. Lett. 383, 241-245 https://doi.org/10.1016/j.neulet.2005.04.054
  48. Van der Borght, K., J. Mulder, J. N. Keijser, B. J. Eggen, P. G. Luiten, and E. A. Van der ZeeE. 2005. Input from the medial septum regulates adult hippocampal neurogenesis. Brain Res. Bull. 67, 117-125 https://doi.org/10.1016/j.brainresbull.2005.06.018
  49. van Praag, H., B. R. Christie, T. J. Sejnowski, and F. H. 1999. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc. Natl. Acad. Sci. 96, 13427-13431 https://doi.org/10.1073/pnas.96.23.13427
  50. van Praag, H., G. Kempermann, and F. H. Gage. 2004. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2, 266-270 https://doi.org/10.1038/6368
  51. Vaynman, S., Z. Ying, and F. Gomez-Pinilla. 2004. Exercise induces BDNF and synapsin I to specific hippocampal subfields. J. Neurosci. Res. 76, 356-362 https://doi.org/10.1002/jnr.20077
  52. Wagatsuma, H. and Y. Yamaguchi. 2007. Neural dynamics of the cognitive map in the hippocampus. Cogn. Neurodyn. 2, 119-141 https://doi.org/10.1007/s11571-006-9013-6
  53. Wolfer, D. P. and H. P. Lipp. 1995. Evidence for physiological growth of hippocampal mossy fiber collaterals in the guinea pig during puberty and adulthood. Hippocampus 5, 329-340 https://doi.org/10.1002/hipo.450050406
  54. Wu, C. W., Y. T. Chang, L. Yu, H. I. Chen, C. J. Jen, S. Y. Wu, C. P. Lo, and Y. M. Kuo. 2008. Exercise enhances the proliferation of neural stem cells and neurite growth and survival of neuronal progenitor cells in dentate gyrus of middle-aged mice. J. Appl. Physiol. 105, 1585-1594 https://doi.org/10.1152/japplphysiol.90775.2008

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