뇌손상 흰쥐에서 기억과 학습훈련이 해마의 신경 성장인자에 미치는 영향

Effects of Memory and Learning Training on Neurotropic Factor in the Hippocampus after Brain Injury in Rats

  • 허명 (광주대학교 작업치료학과) ;
  • 방요순 (광주대학교 작업치료학과)
  • 발행 : 2009.02.28


본 연구는 뇌손상 흰쥐에서 기억과 학습훈련을 통해 인지기능회복과 해마의 신경 성장인자에 미치는 영향을 알아보고자 하였다. 뇌손상은 Sprague-Dawley계 흰쥐 36마리를 중대뇌동맥(middle cerebral artery)을 폐색하여 유발하였고, 실험 군들은 3개 군으로 분류하였다; 실험 군 I은 뇌손상유발 군(n=12), 실험 군 II는 뇌손상 유발 후 트레드밀훈련 군(n=12), 실험 군 Ⅲ은 뇌손상 유발 후 기억과 학습훈련 군(n=12)으로 나누었다. 인지기능 검사를 위해 수중모리스미로 습득검사와 파지검사를 실시하였으며, 조직학적 검사는 해마조직의 BDNF(brain-derived neurotrophic factor) 면역조직화학 반응을 관찰하였다. 수중모리스미로 습득 검사(Morris water maze acquisition test)는 시간과 군사이의 교호작용이 유의한 차이가 나타났고(p<.001), III군에서 9일에서 12일째까지 원형도피대를 찾는 시간이 I, II군에 비해 단축되었다. 수중모리스미로 파지검사(retention test)는 군 사이에서도 유의한 차이가 나타났으며(p<.001), 13일째 III군에서 원형도피대가 있었던 사분원에 배회하는 시간이 가장 길었다. 조직학적 검사는 III군에서 7일째 해마조직의 CA1에서 BDNF의 면역조직화학반응이 I, II군에 비해 면역양성반응의 증가를 관찰하였다. 뇌손상 흰쥐에서 기억과 학습훈련이 신경성장인자 발현 변화와 이로 인한 신경연접 가소성의 변화를 통해 인지기능회복에 더 좋은 영향을 주었다.


  1. M. Kotila, O. Waltimo, M. L. Niemi, R. Laaksonen, and M. Lempinen, "The profile of recovery from stroke and factors influencing outcome," Stroke, Vol.15, No.6, pp.1039-1044, 1984.
  2. P. M. Pedersen, H. S. Jorgensen, H. Nakayama, H. O. Raaschou, and T. S. Olsen, "Orientation in the acute and chronic stroke patient: impact on ADL and social activities. The Copenhagen Stroke Study," Arch Phys Med Rehabil, Vol.77, No.4, pp.336-339, 1996.
  3. N. R. Sims and M. F. Anderson, "Mitochondrial contributions to tissue damage in stroke," Neurochem Int, Vol.40, No.6, pp.511-526, 2002.
  4. W. K. Tang, S. S. Chan, H. F. Chiu, G. S. Ungvari, K. S. Wong, T. C. Kwok, V. Mok, K. T. Wong, P. S. Richards, and A. T. Ahuja, "Frequency and determinants of prestroke dementia in a Chinese cohort," J Neurol, Vol.251, No.5, pp.604-608, 2004.
  5. D. H. Zhou, J. Y. Wang, J. Li, J. Deng, C. Gao, and M. Chen, "Frequency and risk factors of vascular cognitive impairment three months after ischemic stroke in china: the Chongqing stroke study," Neuroepidemiology, Vol.24, No.1-2, pp.87-95, 2005.
  6. Q. Tang, Q. Yang, Z. Hu, B. Liu, J. Shuai, G. Wang, Z. Liu, J. Xia, and X. Shen, "The effects of willed movement therapy on AMPA receptor properties for adult rat following focal cerebral ischemia," Behav Brain Res, Vol.181, No.2, pp.254-261, 2007.
  7. Y. Fang, X. Chen, H. Li, J. Lin, R. Huang, and J. Zeng, "A study on additional early physiotherapy after stroke and factors affecting functional recovery," Clin Rehabil, Vol.17, No.6, pp.608-617, 2003.
  8. M. J. Lister, Contemporary Management of Motor Control Problems: Proceedings of the II STEP Conference. Alexandria, Va: Foundation of physical Therapy, 1991.
  9. C. J. Winstein, D. K. Rose, S. M. Tan, R. Lewthwaite, H. C. Chui, and S. P. Azen, "A randomized controlled comparison of upper-extremity rehabilitation strategies in acute stroke: A pilot study of immediate and long-term outcomes," Arch Phys Med Rehabil, Vol.85, No.4, pp.620-628, 2004.
  10. B. Connor and M. Dragunow, "The role of neuronal growth factors in neurodegenerative disorders of the human brain," Brain Res Brain Res Rev, Vol.27, No.1, pp.1-39, 1998.
  11. A. K. McAllister, L. C. Katz, and D. C. Lo, "Neurotrophins and synaptic plasticity," Annu Rev Neurosci, Vol.22, pp.295-318, 1999.
  12. C. W. Cotman and N. C. Berchtold, "Exercise: a behavioral intervention to enhance brain health and plasticity," Trends Neurosci, Vol.25, No.6, pp.295-301, 2002.
  13. T. A. Jones, C. J. Chu, L. A. Grande, and A. D. Gregory, "Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats," J Neurosci, Vol.19, No.22, pp.10153-10163, 1999.
  14. Z. Radak, T. Kaneko, S. Tahara, H. Nakamoto, J. Pucsok, M. Sasvari, C. Nyakas, and S. Goto, "Regular exercise improves cognitive function and decreases oxidative damage in rat brain," Neurochem Int, Vol.38, No.1, pp.17-23, 2001.
  15. Y. R. Yang, R. Y. Wang, P. S. Wang, and S. M. Yu, "Treadmill training effects on neurological outcome after middle cerebral artery occlusion in rats," Can J Neurol Sci, Vol.30, No.3, pp.252-258, 2003.
  16. J. L. Trejo, E. Carro, and I. Torres-Aleman, "Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus," J Neurosci, Vol.21, No.5, pp.1628-1634, 2001.
  17. J. B. Bederson, L. H. Pitts, M. Tsuji, M. C. Nishimura, R. L. Davis, and H. Bartkowski, "Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination," Stroke, Vol.17, No.3, pp.472-476, 1986.
  18. H. Nagasawa and K. Kogure, "Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion," Stroke, Vol.20, No.8, pp.1037-1043, 1989.
  19. Y. P. Kim, H. B. Kim, M. H. Jang, B. V. Lim, Y. J. Kim, H. Kim, S. S. Kim, E. H. Kim, and C. J. Kim, "Magnitude- and time-dependence of the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats," Int J Sports Med, Vol.24, No.2, pp.114-117, 2003.
  20. I. S. Hairston, M. T. Little, M. D. Scanlon, M. T. Barakat, T. D. Palmer, R. M. Sapolsky, and H. C. Heller, "Sleep restriction suppresses neurogenesis induced by hippocampusdependent learning, J Neurophysiol," Vol.94, No.6, pp.4224-4233, 2005.
  21. A. Fukunaga, K. Uchida, K. Hara, Y. Kuroshima, and T. Kawase, "Differentiation and angiogenesis of central nervous system stem cells implanted with mesenchyme into ischemic rat brain," Cell Transplant, Vol.8, No.4, pp.435-441, 1999.
  22. J. Jolkkonen, N. P. Gallagher, K. Zilles, and J. Sivenius, "Behavioral deficits and recovery following transient focal cerebral ischemia in rats: glutamatergic and GABAergic receptor densities," Behav Brain Res, Vol.138, No.2, pp.187-200, 2003.
  23. L. R. Squire and S. M. Zola, "Ischemic brain damage and memory impairment: a commentary," Hippocampus, Vol.6, No.5, pp.546-552, 1996.<546::AID-HIPO7>3.0.CO;2-G
  24. C. X. Luo, J. Jiang, Q. G. Zhou, X. J. Zhu, W. Wang, Z. J. Zhang, X. Han, and D. Y Zhu, "Voluntary exercise-induced neurogenesis in the postischemic dentate gyrus is associated with spatial memory recovery from stroke," J Neurosci Res, Vol.85, No.8, pp.1637-1646, 2007.
  25. B. Milner, L. R. Squire, and E. R. Kandel, "Cognitive neuroscience and the study of memory," Neuron, Vol.20, No.3, pp.445-468, 1998.
  26. H. van Praag, G. Kempermann, and F. H. Gage, "Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus," Nat Neurosci, Vol.2, No.3, pp.266-270, 1999.
  27. H. Soya, T. Nakamura, C. C. Deocaris, A. Kimpara, M. Iimura, T. Fujikawa, H. Chang, B. S. McEwen, and T. Nishijima, "BDNF induction with mild exercise in the rat hippocampus," Biochem Biophys Res Commun, Vol.358, No.4, pp.961-967, 2007.
  28. B. Leuner, S. Mendolia-Loffredo, Y. Kozorovitskiy, D. Samburg, E. Gould, and T. J. Shors, "Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory," J Neurosci, Vol.24, No.34, pp.7477-7481, 2004.
  29. M. D. Dobrossy, E. Drapeau, C. Aurousseau, M. Le Moal, P. V. Piazza, and D. N. Abrous, "Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date," Mol Psychiatry, Vol.8, No.12, pp.974-982, 2003.
  30. P. Mohapel, K. Mundt-Petersen, P. Brundin, and H. Frielingsdorf, "Working memory training decreases hippocampal neurogenesis," Neuroscience, Vol.142, No.3, pp.609-613, 2006.
  31. M. W. Kim, M. S. Bang, T. R. Han, Y. J. Ko, B. W. Yoon, J. H. Kim, L. M. Kang, K. M. Lee, and M. H. Kim, "Exercise increased BDNF and trkB in the contralateral hemisphere of the ischemic rat brain," Brain Res, Vol.1052, No.1, pp.16-21, 2005.
  32. J. Dickson, Proprioceptive control of human movement. London: Lepus Books, 1974.
  33. D. H. Holding, Principles of training. London: Pergamon Press, 1965.