DOI QR코드

DOI QR Code

Effect of Exercise on Neurotrophins, BDNF, NT-3, GAP43 Protein Expression and Axonal Regeneration after Sciatic Nerve Injury in F344 Rats

운동이 좌골신경 손상 F344쥐의 Neurotrophins, BDNF, NT-3, GAP-43 단백질 발현과 축삭재생에 미치는 영향

  • Yoon Jin-Hwan (Department of Sports and Leisure Studies, Hannam University) ;
  • Seo Tae-Beom (Department of Sports and Leisure Studies, Hannam University)
  • 윤진환 (한남대학교 생활체육학과) ;
  • 서태범 (한남대학교 생활체육학과)
  • Published : 2006.06.01

Abstract

Peripheral nerve injuries are a commonly encountered clinical problem and often result in severe functional deficits. In the present study, the effects of treadmill exercise on neurotrophin expressions and functional recovery following sciatic crushed nerve injury were investigated. Animals were randomly assigned into four groups: the sciatic nerve injury group, the sciatic nerve injury and 3-day-exercise, the sciatic nerve injury and 7-days-exercise, and the sciatic nerve injury and 14-days-exercise groups. Sciatic nerve injury was caused by crushing the right sciatic nerve for 30 s using a surgical clip. A the light-exercise was applied to each of the exercise group over the respective number of days. In the present results, we identified enhanced axonal re-growth in the distal stump of the sciatic nerve 3-14 days after crush injury with treadmill training. Dorsal root ganglion (DRG) neuron when cultured from animals with nerve injury and treadmill training showed more enhanced neurite outgrowth than that of sedentary animals. Nerve growth factor (NGF) protein levels in low-intensity treadmill training group were highly induced in the injured sciatic nerves 3, 7 and 14 days after injury compared with sedentary group, and brain-derived neurotrophin factor (BDNF) protein levels in treadmill exercise group were highly induced in the injured sciatic nerve 3 days after injury compared with sedentary group. Then, treadmill exercise increased neurotrophic factors induced in the regenerating nerves. We further demonstrate that motor functional recovery after sciatic nerve injury was promoted by treadmill exercise. Thus, the present data provide a new evidence that treadmill exercise enhanced neurotrophins expression and axonal regeneration after sciatic nerve injury in rats.

본 연구에서는 흰쥐의 좌골신경을 손상시킨 후 트레드밀 운동을 적용하여 신경돌기 성장과 좌골신경의 축삭 재생 및 신경성장 인자 발현 그리고 신경기능지수의 변화를 연구했다. 본 연구결과 좌골손상 후 트레드밀 운동을 실시한 그룹이 비운동군에 비해 축삭재생이 촉진되었고, 원위부의 좌골신경에서도 NGF, BDNF단백질 발현이 상당히 증가된 것으로 나타났다. 또한 좌골신경지수를 검사한 결과에서도 운동을 실시한 흰쥐가 비운동 흰쥐에 비해 기능적 회복이 상당히 빠른 것으로 나타났다. 이러한 결과는 좌골손상 후 운동의 실시가 좌골신경의 축삭재생 촉진과 신경영양인자의 발현증가를 통해 기능적 회복에 도움이 될 수 있음을 보여주는 것이다.

Keywords

References

  1. Akassoglou, K., W. M. Yu, P. Akpinar and S. Strickland. 2002. Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation. Neuron 33, 861-875 https://doi.org/10.1016/S0896-6273(02)00617-7
  2. Bain, J. R., S. E. Mackinnon and D. A. Hunter. 1989. Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plastic and Reconstructive Surgery 83, 129-138 https://doi.org/10.1097/00006534-198901000-00024
  3. Barde, Y. A., D. Edgar and H. Thoenen. 1982. Purification of a new neurotrophic factor from mammalian brain. EMBO Journal 1, 549-553
  4. Barres, B. A., M. C. Raff, F. Gaese, I. Bartke, G. Dechant and Y. A. Barde. 1994. A crucial role for neurotrophin-3 in oligodendrocyte development. Nature 367, 371-375 https://doi.org/10.1038/367371a0
  5. Bentley, C. A. & K. F. Lee. 2000. p75 is important for axon growth and schwann cell migration during development. Journal of Neuroscience 20, 7706-7715 https://doi.org/10.1523/JNEUROSCI.20-20-07706.2000
  6. Canossa, M., A. Gartner, G. Campana, N. Inagaki and H. Thoenen. 2001. Regulated secretion of neurotrophins by metabotropic glutamate troup I (mGluRI) and TRK receptor activation is mediated via phospholipase C signaling pathways. EMBO Journal 20, 1640-1650 https://doi.org/10.1093/emboj/20.7.1640
  7. Fawcett, J. W. and R. J. Keynes. 1990. Peripheral nerve regeneration. Annual Review of Neuroscience 13, 43-60 https://doi.org/10.1146/annurev.ne.13.030190.000355
  8. Funakoshi, H., J. Frisen, G. Barbany, T. Timmusk, O. Zachrisson, V. M. Verge and H. Persson. 1993. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. Journal of Cell Biology 123, 455-465 https://doi.org/10.1083/jcb.123.2.455
  9. Gillen, C., C. Korfhage and H. W. Muller. 1997. Gene expression in nerve regeneration. Neuroscientist 3, 112-122 https://doi.org/10.1177/107385849700300210
  10. Gold, B. G., W. C. Mobley and S. F. Matheson. 1991. Regulation of axonal caliber, neurofilament content, and nuclear localization in mature sensory neurons by nerve growth factor. Journal of Neuroscience 11, 943-955 https://doi.org/10.1523/JNEUROSCI.11-04-00943.1991
  11. Gomez-Pinilla, F., Z. Ying, P. Opazo, R. R. Roy and V. R. Edgerton. 2001. Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. European Journal of Neuroscience 13, 1078-1084 https://doi.org/10.1046/j.0953-816x.2001.01484.x
  12. Gomez-Pinilla, F., Z. Ying, R. Roy, R. Molteni and V. Edgerton. 2002. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. Journal of Neurophysiology 88, 2187-2195 https://doi.org/10.1152/jn.00152.2002
  13. Heumann, R., S. Korsching, C. Bandtlow and H. Thoenen. 1987. Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection. Journal of Cell Biology 104, 1623-1631 https://doi.org/10.1083/jcb.104.6.1623
  14. Klintsova, A. Y. and W. T. Greenough. 1999. Synaptic plasticity in cortical systems. Current Opinion in Neurobiology 9, 203-208 https://doi.org/10.1016/S0959-4388(99)80028-2
  15. Lefcort, F., K. Venstrom, J. A. McDonald and L. F. Reichardt. 1992. Regulation of expression of fibronectin and its receptor, 51, during development and generation of peripheral nerve. Development 116, 767-782
  16. Lemke, G. 2001 Glial control of neuronal development. Annual Review of Neuroscience 24, 87-105 https://doi.org/10.1146/annurev.neuro.24.1.87
  17. Lewin, G. R. and Y. A. Barde. 1996. Physiology of the neurotrophins. Annual Review of Neuroscience 19, 289-317 https://doi.org/10.1146/annurev.ne.19.030196.001445
  18. Martini, R. 2001. The effectof myelinating Schwann cells on axons. Muscle Nerve 24, 456-466 https://doi.org/10.1002/mus.1027
  19. McAllister, A., L. C. Katz and D. Lo. 1999. Neurotrophins andsynaptic plasticity. Annual Review of Neuroscience 22, 295-318 https://doi.org/10.1146/annurev.neuro.22.1.295
  20. Mirsky, R. and K. R. Jessen. 1996. Schwann cell development, differentiation and myelination. Current Opinion in Neurobiology 6, 89-96 https://doi.org/10.1016/S0959-4388(96)80013-4
  21. Miyata, H. and H. Itoh. 1986. CNS changes in the meconium aspiration syndrome. Kobe Journal of Medical Sciences 32, 179-195
  22. Molteni, R., J. Q. Zheng, Z. Ying, F. Gomez-Pinilla and J. L. Twiss. 2004. Voluntary exercise increases axonal regeneration from sensory neurons. Proceedings of the National Academy of Sciences of the United States of America 101, 8473-8478
  23. Nico. L. U., P. T. van Meeteren, B. S. Brakkee, P. J. Hamers & W. H. Gispen. 1997. Exercise Training improves functional recovery and motor nerve conduction velocity after sciatic nervecrush lesion in the rat. Archives of Physical Medicine and Rehabilitation 78, 70-77 https://doi.org/10.1016/S0003-9993(97)90013-7
  24. Nieke, J. and M. Schachner. 1985. Expression of the neural cell adhesion molecules L1 and N-CAM and their common carbohydrate epitope L2/HNK-1 during development and after transection of the mouse sciatic nerve. Differentitation 30, 141-151 https://doi.org/10.1111/j.1432-0436.1985.tb00525.x
  25. Raffaella, R., D. Gioia, M. De Andrea, P. Cappello, M. Giovarelli, P. Marconi, R. Manservigi, M. Gariglio and S. Landolfo. 2004. The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells. Experimental Cell Research 293, 331-345 https://doi.org/10.1016/j.yexcr.2003.10.014
  26. Schwab, M. E. 2000. Neurobiology. Finding the lost target. Nature 257, 259-260
  27. Sendtner, M., B. Holtmann, R. Kolbeck, H. Thoenen and Y. A. Barde. 1992. Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature 360, 757-759 https://doi.org/10.1038/360757a0
  28. Tetzlaff, W., N. R. Kobayashi, K. M. Giehl, B. J. Tsui, S. L. Cassar and A. M. Bedard. 1994. Response of rubrospinal and corticospinal neurons to injury and neurotrophins. Progress in Brain Research 103, 271-286 https://doi.org/10.1016/S0079-6123(08)61142-5
  29. Thompson, S. W. N., D. L. H. Bennet, B. J. Kerr, E. J. Bradbury and S. B. McMahon. 1999. Brain-derived neurotrophic factor is an endogenous modulator of nociceptive responses in the spinal cord. Proceedings of the National Academy of Sciences of the United States of America 96, 7714-7718
  30. van Meeteren N. L., J. H. Brakkee, P. J. Helders and W. H. Gispen. 1998. The effect of exercise training on functional recovery after sciatic nerve crush in the rat. Journal of the Peripheral Nervous System 3, 277-282
  31. van Meeteren, N. L., J. H. Brakkee, P. J. Helders, G. Croiset, W. H. Gispen, and V. M. Wiegant. 1997. Recovery of function after sciatic nerve crush lesion in rats selected for diverging locomotor activity in the open field. Neuroscience Letters 238, 131-134 https://doi.org/10.1016/S0304-3940(97)00870-7
  32. Ying, Z., R. R. Roy, V. R. Edgerton and F. Gomez-Pinilla. 2003. Voluntary exercise increases neurotrophin-3 and its receptor TrkC in the spinal cord. Brain Resource 987, 93-99 https://doi.org/10.1016/S0006-8993(03)03258-X
  33. Zhang,J. Y., X. G. Luo, C. J. Xian, Z. H. Liu and X. F. Ahou. 2000. Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents. European Journal of Neuroscience 12, 4171-4180