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Effects of Exercise Preconditioning on the Expression of NGF, Synapsin I, and ChAT in the Hippocampus of Socially Isolated Rats

사회적으로 고립된 쥐의 해마에서 NGF와 Synapsin I, ChAT의 단백질 수준에 미치는 사전운동효과

  • Hong, Young-Pyo (Department of Health and Exercise Science, Korea National Sport University) ;
  • Kim, Hyun-Tae (Department of Health and Exercise Science, Korea National Sport University)
  • 홍영표 (한국체육대학교 한국체육대학교) ;
  • 김현태 (한국체육대학교 한국체육대학교)
  • Received : 2012.05.23
  • Accepted : 2012.08.29
  • Published : 2012.09.30

Abstract

The purpose of this study was to investigate the effect of exercise preconditioning (EPC) on nerve growth factor (NGF), synapsin I, and choline acetyltransferase (ChAT) in the hippocampus of rats subjected to social isolation (SI). We randomly assigned four groups of male Sprague-Dawley (SD) rats (n=32) to the following treatments: GC: group housing control; IC: isolation control; GE: group housing exercise; IE: isolation exercise (n=8 each group). The rats underwent EPC 5 days a week for 8 weeks, and the speed of the treadmill was gradually increased (grade $0^{\circ}C$). After EPC, they were immediately subjected to SI for 8 weeks. The results showed that the protein levels of NGF, synapsin I, and ChAT in the hippocampus were significantly decreased in the IC group (p<0.05) compared with the GC group. However, these protein levels were significantly higher in the IE group (p<0.05). These results show that EPC may buffer the decline of function in the hippocampus by ameliorating the reduction in NGF, synapsin I, and ChAT induced by SI.

본 연구는 사회적 고립 스트레스로 인한 해마에서의 nerve growth factor (NGF), Synapsin I 및 choline acetyltranferase (ChAT) 감소에 있어서 사전운동경험(exercise preconditioning: EPC)이 미치는 영향을 규명하고자 실시되었다. 목적을 위해 Sprague-Dawley (SD) 쥐(수컷, 22주령, $500.1{\pm}48.41$ g)를 이용해 크게 통제집단(Con)과 운동(Ex)집단으로 구분하여 운동(트레드밀, 5일/주, 최대 18-20 m/min; 50분까지 점진적 증가, 경사 없음, 8주)을 적용하였으며, 이후 각각 사회적 고립(Isolation, 8주)을 적용하여 분석하였다(Group/Con: GC, Group/Ex: GE, Isolation/Con: IC, Isolation/Ex: IE, 각 집단별 n=8). 실험결과, IC집단에서 GC집단에 비해 해마에서 NGF, Synapsin I 및 ChAT가 유의하게 감소한 것으로 나타났다. 반면 IE집단에서 IC집단에 비해 NGF, Synapsin I 및 ChAT의 감소가 유의하게 개선된 것으로 나타났다. 이상의 결과 사회적 고립에 의한 해마에서의 NGF, Synapsin I 및 ChAT 단백질 감소는 EPC에 의해 개선되며, 이를 통해 해마의 기능 저하를 일부 완충 시킬 수 있을 것으로 판단된다.

Keywords

References

  1. Ang, E. T., Wong, P. T., Moochhala, S. and Ng, Y. K. 2003. Neuroprotection associated with running: Is it a result of increased endogenous neurotrophic factors? Neuroscience 118, 335-345. https://doi.org/10.1016/S0306-4522(02)00989-2
  2. Belarbi, K., Schindowski, K., Burnouf, S., Caillierez, R., Grosjean, M. E., Demeyer, D., Hamdane, M., Sergeant, N., Blum, D. and Buée, L. 2009. Early Tau pathology involving the septo-hippocampal pathway in a Tau transgenic model: relevance to Alzheimer's disease. Curr. Alzheimer. Res. 6, 152-157. https://doi.org/10.2174/156720509787602843
  3. Belarbi, K., Burnouf, S., Fernandez-Gomez, F. J., Laurent, C., Lestavel, S., Figeac, M., Sultan, A., Troquier, L., Leboucher, A., Caillierez, R., Grosjean, M. E., Demeyer, D., Obriot, H., Brion, I., Barbot, B., Galas, M. C., Staels, B., Humez, S., Sergeant, N., Schraen-Maschke, S., Muhr-Tailleux, A., Hamdane, M., Buée, L. and Blum, D. 2011. Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology. Neurobiol. Dis. 43, 486-494. https://doi.org/10.1016/j.nbd.2011.04.022
  4. Belarbi, K., Burnouf, S., Fernandez-Gomez, F. J., Desmercières, J., Troquier, L., Brouillette, J., Tsambou, L., Grosjean, M. E., Caillierez, R., Demeyer, D., Hamdane, M., Schindowski, K., Blum, D. and Buee, L. 2011. Loss of medial septum cholinergic neurons in THY-Tau22 mouse model: what links with tau pathology? Curr. Alzheimer. Res. 8, 633-638. https://doi.org/10.2174/156720511796717230
  5. Bogen, I. L., Haug, K. H., Roberg, B., Fonnum, F. and Walaas, S. I. 2009. The importance of synapsin I and II for neurotransmitter levels and vesicular storage in cholinergic, glutamatergic and GABAergic nerve terminals. Neurochem. Int. 55, 13-21. https://doi.org/10.1016/j.neuint.2009.02.006
  6. Caspi, A., Harrington, H., Moffitt, T. E., Milne, B. J. and Poulton, R. 2006. Socially isolated children 20 years later. Arch. Pediatr. Adolesc. Med. 160, 805-811. https://doi.org/10.1001/archpedi.160.8.805
  7. Chae, C. H. and Kim, H. T. 2009. Forced, moderate- intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3- kinase signaling in the hippocampus of induced aging rats. Neurochem. Int. 55, 208-213. https://doi.org/10.1016/j.neuint.2009.02.024
  8. Corradi, A., Zanardi, A., Giacomini, C., Onofri, F., Valtorta, F., Zoli, M. and Benfenati, F. 2008. Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment. J. Cell Sci. 121, 3042-3051. https://doi.org/10.1242/jcs.035063
  9. Cotman, C. W. and Berchtold, N. C. 2002. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 25, 295-301. https://doi.org/10.1016/S0166-2236(02)02143-4
  10. Fabel, K. and Kempermann, G. 2008. Physical activity and the regulation of neurogenesis in the adult and aging brain. Neuromolecular Med. 10, 59-66. https://doi.org/10.1007/s12017-008-8031-4
  11. Filipovic, D., Gavrilovic, L., Dronjak, S. and Radojcic, M. B. 2007. The effect of repeated physical exercise on hippocampus and brain cortex in stressed rats. Ann. NY Acad. Sci. 1096, 207-219. https://doi.org/10.1196/annals.1397.087
  12. Fone, K. C. and Porkess, M. V. 2008. Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders. Neurosci. Biobehav. Rev. 32, 1087-1102. https://doi.org/10.1016/j.neubiorev.2008.03.003
  13. Frielingsdorf, H., Simpson, D. R., Thal, L. J. and Pizzo, D. P. 2007. Nerve growth factor promotes survival of new neurons in the adult hippocampus. Neurobiol. Dis. 26, 47-55. https://doi.org/10.1016/j.nbd.2006.11.015
  14. Grippo, A. J., Gerena, D., Huang, J., Kumar, N., Shah, M., Ughreja, R. and Carter, C. S. 2007. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles. Psychoneuroendocrinology 32, 966-980. https://doi.org/10.1016/j.psyneuen.2007.07.004
  15. Hermes, G., Li, N., Duman, C. and Duman, R. 2010. Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats. Physiol. Behav. 104, 354-359.
  16. Ibi, D., Takuma, K., Koike, H., Mizoguchi, H., Tsuritani, K., Kuwahara, Y., Kamei, H., Nagai, T., Yoneda, Y., Nabeshima, T. and Yamada, K. 2008. Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice. J. Neurochem. 105, 921-932. https://doi.org/10.1111/j.1471-4159.2007.05207.x
  17. Kempermann, G., Fabel, K., Ehninger, D., Babu, H., Leal-Galicia, P., Garthe, A. and Wolf, S. A. 2010. Why and how physical activity promotes experience-induced brain plasticity. Front Neurosci. 4, 189.
  18. Leasure, J. L. and Decker, L. 2009. Social isolation prevents exercise-induced proliferation of hippocampal progenitor cells in female rats. Hippocampus 19, 907-912. https://doi.org/10.1002/hipo.20563
  19. Liebelt, B., Papapetrou, P., Ali, A., Guo, M., Ji, X., Peng, C., Rogers, R., Curry, A., Jimenez, D., and Ding, Y. 2010. Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated-kinase 1/2. Neuroscience 166, 1091-1100. https://doi.org/10.1016/j.neuroscience.2009.12.067
  20. Lim, A. L., Taylor, D. A. and Malone, D. T. 2011. Isolation rearing in rats: Effect on expression of synaptic, myelin and GABA-related immunoreactivity and its utility for drug screening via the subchronic parenteral route. Brain Res. 1381, 52-65. https://doi.org/10.1016/j.brainres.2011.01.017
  21. Lu, L., Bao, G., Chen, H., Xia, P., Fan, X., Zhang, J., Pei, G. and Ma, L. 2003. Modification of hippocampal neurogenesis and neuroplasticity by social environments. Exp. Neurol. 183, 600-609. https://doi.org/10.1016/S0014-4886(03)00248-6
  22. McEwen, B. S. 1999. Stress and hippocampal plasticity. Annu. Rev. Neurosci. 22, 105-122. https://doi.org/10.1146/annurev.neuro.22.1.105
  23. Mitra, R., Sundlass, K., Parker, K. J., Schatzberg, A. F. and Lyons, D. M. 2006. Social stress-related behavior affects hippocampal cell proliferation in mice. Physiol. Behav. 89, 123-127. https://doi.org/10.1016/j.physbeh.2006.05.047
  24. Neeper, S. A., Gomez-Pinilla, F., Choi, J. and Cotman, C. W. 1996. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 726, 49-56. https://doi.org/10.1016/0006-8993(96)00273-9
  25. Park, H. J., Han, S. M., Yoon, W. J., Kim, K. S. and Shim, I. 2009. The effects of puerariae flos on stress-induced deficits of learning and memory in ovariectomized female rats. Kor. J. Physiol. Pharmacol. 13, 85-89. https://doi.org/10.4196/kjpp.2009.13.2.85
  26. Pizzo, D. P. and Thal, L. J. 2004. Intraparenchymal nerve growth factor improves behavioral deficits while minimizing the adverse effects of intracerebroventricular delivery. Neuroscience 123, 743-755. https://doi.org/10.1016/j.neuroscience.2003.10.020
  27. Ploughman, M. 2008. Exercise is brain food: the effects of physical activity on cognitive function. Dev. Neurorehabil. 11, 236-240. https://doi.org/10.1080/17518420801997007
  28. Rozanski, A., Blumenthal, J. A. and Kaplan, J. 1999. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 99, 2192-2217. https://doi.org/10.1161/01.CIR.99.16.2192
  29. Scaccianoce, S., Bianco, P. D., Paolone, G., Caprioli, D., Modafferi, A. M. E., Nencini, P. and Badiani, A. 2006. Social isolation selectively reduces hippocampal brain-derived neurotrophic factor without altering plasma corticosterone. Behav. Brain Res. 168, 323-325. https://doi.org/10.1016/j.bbr.2005.04.024
  30. Stranahan, A. M., Khalil, D. and Gould, E. 2006. Social isolation delays the positive effects of running on adult neurogenesis. Nat. Neurosci. 9, 526-533. https://doi.org/10.1038/nn1668
  31. Takei, Y., Harada, A., Takeda, S., Kobayashi, K., Terada, S., Noda, T., Takahashi, T. and Hirokawa, N. 1995. Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system. J. Cell Biol. 131, 1789-1800. https://doi.org/10.1083/jcb.131.6.1789
  32. van Praag, H. 2009. Exercise and the brain: something to chew on. Trends Neurosci. 32, 283-290. https://doi.org/10.1016/j.tins.2008.12.007
  33. White, L. J. and Castellano, V. 2008. Exercise and brain health-implications for multiple sclerosis: Part 1-- neuronal growth factors. Sports Med. 38, 91-100. https://doi.org/10.2165/00007256-200838020-00001
  34. Zhang, F., Wu, Y. and Jia, J. 2011. Exercise preconditioning and brain ischemic tolerance. Neuroscience 177, 170-176. https://doi.org/10.1016/j.neuroscience.2011.01.018
  35. Zhu, S. W., Pham, T. M., Aberg, E., Brené, S., Winblad, B., Mohammed, A. H. and Baumans, V. 2006. Neurotrophin levels and behaviour in BALB/c mice: Impact of intermittent exposure to individual housing and wheel running. Behav. Brain Res. 167, 1-8. https://doi.org/10.1016/j.bbr.2005.02.038

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