Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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The Effects of Treadmill Training on Neurotrophins and Immediately Early Protein in Obese Rats

트레드밀 트레이닝이 비만 쥐의 neurotrophins와 초기발현 단백질에 미치는 영향

  • Woo, Jin-Hee (Department of Physical Education, Dong-A University) ;
  • Shin, Ki-Ok (Department of Physical Education, Dong-A University) ;
  • Yeo, Nam-Heoh (Department of Physical Education, Dong-A University) ;
  • Park, So-Young (Department of Pharmacology, Dong-A University) ;
  • Kang, Sung-Hwun (Department of Physical Education, Dong-A University)
  • Received : 2011.04.05
  • Accepted : 2011.07.15
  • Published : 2011.07.30
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Abstract

The purpose of this study was to investigate the biological effect of obesity-induced oxidative damage on neurogenesis and early protein expression. Obesity was induced I thirty 4-week old male Sprague-Dawley rats through a high fat diet for 15 weeks. After one week of environmental adaptation, the rats were divided into 2 groups: high fat diet sedentary group (HDS, n=15) and high fat diet training group (HDT, n=15). Exercise training was performed 5 times a week for 8 weeks, with mild-intensity treadmill running for weeks 1-4 and moderate-intensity treadmill running for weeks 5-8. After the 8 week training period, we analyzed lipid profiles, serum 8-hydroxyguanosine (8-OHdG), liver tissue malondialdehyde (MDA) related to oxidative damage factors, nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), c-fos, c-jun, and extracellular signal regulated kinase (Erk) in the hippocampus. The results of this study are as follows. There were differences between HDS and HDT in triglyceride (TG) and total cholesterol (TC) (p<0.05). In high density lipoprotein (HDL-c), the HDT was higher than HDS after treadmill training (p<0.05). In 8-OHdG, the HDT was lower than HDS after treadmill training (p<0.05). Genetic expressions of c-jun, BDNF and MDA in the HDT were higher than in the HDS after treadmill training in hippocampus (p<0.05). Therefore, we conclude that 8 weeks of treadmill training can improve imbalanced lipid profiles, reduce oxidative damage, and activate neurogenesis in obese rats.

본 연구는 고지방식이로 인한 비만으로 불균형된 지질구성과 산화적 손상이 신경세포형성과 초기발현단백질에 미치는 생물학적 영향을 알아보고, 규칙적인 운동의 효과를 알아보기 위하여 실시하였다. 실험동물은 4주령 SD rat 수컷 30마리를 1주간의 적응기간을 둔 뒤, 15주간 고지방식이를 통해 비만으로 유도하였으며, high fat diet sedentary (HDS, n=15)와 high fat diet and training (HDT, n=15)으로 분류하여 연구하였다. 운동강도는 1~4주는 저강도, 5~8주는 중강도로 주5회 실시하였다. 8주 트레이닝 후 혈청지질, 8-OHdG, MDA, neurotrophic factor, 그리고 IEG를 분석하였다. 그 결과 TC와 TG에서 HDS와 HDT 사이 유의한 차이가 나타났다(p<0.05). 8-OHdG에서 HDT는 트레드밀 트레이닝 후에 HDS보다 낮게 나타났다(p<0.05). 해마에서 c-jun, BDNF 그리고 간에서 MDA의 단백질 발현은 HDT가 트레드밀 트레이닝 후 HDS보다 높게 나타났다(p<0.05). 결론적으로 8주간 트레드밀 훈련은 고지방식이 비만 유도 쥐의 혈청지질 성분의 불균형을 개선시키고, 조직과 혈청의 산화적 손상과 DNA 손상을 완화시켜 주어, 비만으로 인한 합병증 예방에 도움을 줄 수 있을 것으로 사료된다. 또한 NT의 발현을 증가시킴으로써 손상된 뇌기능과 신경세포의 생성 기전 활동에 긍정적 영향을 나타냄으로써 공간적 학습기능의 향상을 가져온 것으로 판단된다.

Keywords

References

  1. Angel, P. and M. Karin. 1991. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim. Biophys. Acta. 1072, 129-157.
  2. Bogani, P., C. Galli, M. Villa, and F. Visioli. 2007. Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil. Atherosclerosis 190, 181-186. https://doi.org/10.1016/j.atherosclerosis.2006.01.011
  3. Bullo, M., M. R. Peeraully, P. Trayhum, J. Folch, and J. Salas-Salvado. 2007. Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women. Eur. J. Endocrinol. 157, 303-310. https://doi.org/10.1530/EJE-06-0716
  4. Chae, C. H., S. L. Jung, S. H. An, B. Y. Park, S. W. Wang, I. H. Cho, J. Y. Cho, and H. T. Kim. 2009. Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 in the streptozotocin-induced diabetic rat hippocampus. Neuroscience 164, 1665-1673. https://doi.org/10.1016/j.neuroscience.2009.09.075
  5. Chen, L., L. Liu, Y. Luo, and S. Huang. 2008. MAPK and mTOR pathways are involved in cadmium-induced neuronal apoptosis. J. Neurochem. 105, 251-261. https://doi.org/10.1111/j.1471-4159.2007.05133.x
  6. Cotman, C. W. and C. Engesser-Cesar. 2002. Exercise enhances and protects brain function. Exerc. Sport. Sci. Rev. 30, 75-79. https://doi.org/10.1097/00003677-200204000-00006
  7. Derijard, B., M. Hibi, I. H. Wu, T. Barrett, B. Su, T. Deng, M. Karin, and R. J. Davis. 1994. JNK1: a protein kinase stimulated by UV light and Ha-Ras thst bind and phosphorylates the c-jun activation domain. Cell 76, 1025-1037. https://doi.org/10.1016/0092-8674(94)90380-8
  8. Furukawa, S., T. Fujita, M. Shimabukuro, M. Iwaki, Y. Yamada, Y. Nakajima, O. Nakayama, M. Makishima, M. Matsuda, and I. Shimomura. 2004. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 114, 1752-1761. https://doi.org/10.1172/JCI21625
  9. Hebben, N., S. Corkin, H. Eichenbaum, and K. Shedlack. 1985. Diminished ability to interpret and report internal states after bilateral medial temporal resection: case H.M. Behav. Neurosci. 99, 1031-1039. https://doi.org/10.1037/0735-7044.99.6.1031
  10. Heled, Y., Y. Shapiro, Y. Shani, D. S. Moran, L. Langzam, L. Braiman, S. R. Sampson, and J. Meyerovitch. 2002. Physical exercise prevents the development of type 2 diabetes mellitus in Psammomys obesus. Am. J. Physiol. Endocrinol. Metab. 282, E370-E375.
  11. Hempstead, B. L. 2006. Dissecting the diverse actions of proand mature neurotrophins. Curr. Alzheimer. Res. 3, 19-24. https://doi.org/10.2174/156720506775697061
  12. Huang, E. J. and L. F. Reichardt. 2003. Trk receptors: roles in neuronal signal transduction. Annu. Rev. Biochem. 72, 609-642. https://doi.org/10.1146/annurev.biochem.72.121801.161629
  13. Iemitsu, M., S. Maeda, S. Jesmin, T. Otsuki, Y. Kasuya, and T. Miyauchi. 2006. Activation pattern of MAPK signaling in the hearts of trained and untrained rats following a single bout of exercise. J. Appl. Physiol. 101, 151-163. https://doi.org/10.1152/japplphysiol.00392.2005
  14. Kakar, M., H. Nystrom, L. R. Aarup, T. J. Nottrup, and D. R. Olsen. 2005. Respiratory motion prediction by using the adaptive neuro fuzzy inference system (ANFIS). Phys. Med. Biol. 50, 4721-4728. https://doi.org/10.1088/0031-9155/50/19/020
  15. Kanoski, S. E., R. L. Meisel, A. J. Mullins, and T. L. Davidson. 2007. The effects of energy-rich diets on discrimination reversal learning and on BDNF in the hippocampus and prefrontal cortex of the rat. Behav. Brain Res. 182, 57-66. https://doi.org/10.1016/j.bbr.2007.05.004
  16. Kornhauser, J. M., D. E. Nelson, K. E. Mayo, and J. S. Takahashi. 1992. Regulation of jun-B messenger RNA and AP-1 activity by light and a circadian clock. Science 255, 1581-1584. https://doi.org/10.1126/science.1549784
  17. Levinger, I., C. Goodman, V. Matthews, D. L. Hare, G. Jerums, A. Garnham, and S. Selig. 2008. BDNF, metabolic risk factors, and resistance training in middle-aged individuals. Med. Sci. Sports Exerc. 40, 535-541. https://doi.org/10.1249/MSS.0b013e31815dd057
  18. Molteni, R., R. J. Barnard, Z. Yinq, C. K. Roberts, and F. Gómez-Pinilla. 2002. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 112, 803-814. https://doi.org/10.1016/S0306-4522(02)00123-9
  19. Neeper, S. A., F. Gomez-Pinilla, J. Choi, and C. W. Cotman 1995. Exercise and brain neurotrophins. Nature 373, 109. https://doi.org/10.1038/373109a0
  20. Nisoli, E., C. Tonello, M. Benarese, P. Liberini, and M. O. Carruba. 1996. Expression of nerve growth factor in brown adipose tissue: implications for thermogenesis and obesity. Endocrinology 137, 495-503. https://doi.org/10.1210/en.137.2.495
  21. Oladehin, A. and R. S. Waters. 2001. Location and distribution of Fos protein expression in rat hippocampus followting acute moderate aerobic exercise. Exp. Brain. Res. 137, 26-35. https://doi.org/10.1007/s002210000634
  22. Radak, Z., T. Kaneko, S. Tahara, H. Nakamoto, J. Pucsok, M. Sasvari, C. Nyakas, and S. Goto. 2001. Regular exercise imporves cognitive function and decreases oxidative damage in rat brain. Neurochem. Int. 38, 17-23. https://doi.org/10.1016/S0197-0186(00)00063-2
  23. Radak, Z., A.W. Taylor, H. Ohno, and S. Goto. 2001b. Adaptation to exercise induced oxidative stress: from muscle to brain. Exerc. Immunol. Rev. 7, 90-107.
  24. Radak, Z., A. Toldy, Z. Szabo, S. Siamilis, C. Nyakas, G. Silye, J. Jakus, and S. Goto. 2006. The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain. Neurochem. Int. 49, 387-392. https://doi.org/10.1016/j.neuint.2006.02.004
  25. Rajala, M. W. and P. E. Scherer. 2003. Minireview: The adipocyte- at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144, 3765-3773. https://doi.org/10.1210/en.2003-0580
  26. Ruwhof, C. and A. van der Laarse. 2000. Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc. Res. 47, 23-37. https://doi.org/10.1016/S0008-6363(00)00076-6
  27. Schulz, K. H., S. M. Gold, J. Witte, K. Bartsch, U. E. Lang, R. Hellweg, R. Reer, K. M. Braumann, and C. Heesen. 2004. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J. Neurol. Sci. 225, 11-18. https://doi.org/10.1016/j.jns.2004.06.009
  28. Seger, R. and E. G. Krebs. 1995. The MAPK signaling cascade. FASEB. J. 9, 726-735.
  29. Siamilis, S., J. Jakus, C. Nyakas, A. Costa, B. Mihalik, A. Falus, and Z. Radak. 2009. The effect of exercise and oxidant- antioxidant intervention on the levels of neurotrophins and free radicals in spinal cord of rats. Spinal Cord 47, 453-457. https://doi.org/10.1038/sc.2008.125
  30. Sim, K. J., H. Kim, M. S. Shin, H. K. Chang, M. C. Shin, I. G. Ko, K. J. Kim, T. S. Kim, B. K. Kim, Y. T. Rhim, S. Kim, H. Y. Park, J. W. Yi, S. J. Lee, and C. J. Kim 2008. Effect of postnatal treadmill exercise on c-Fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers. Brain Dev. 30, 118-125. https://doi.org/10.1016/j.braindev.2007.07.003
  31. Steers, W. D. and J. B. Tuttle. 2006 Mechanisms of Disease: the role of nerve growth factor in the pathophysiology of bladder disorders. Nat. Clin. Pract. Urol. 3, 101-110. https://doi.org/10.1038/ncpuro0408
  32. Suzuki, K., Y. Ito, J. Ochiai, Y. Kusuhara, S. Hashimoto, S. Tokudome, M. Kojima, K. Wakai, H. Toyoshima, K. Tamakoshi, Y. Watanabe, N. Hayakawa, M. Maruta, M. Watanabe, K. Kato, Y. Ohta, and A. Tamakoshi. 2003. Relationship between obesity and serum markers of oxidative stress and inflammation in Japanese. Asian Pac. J. Cancer Prev. 4, 259-266.
  33. Sweatt, J. D. 2004. Mitogen-activated protein kinases in synaptic plasticity and memory. Curr. Opin. Neurobiol. 14, 311-317. https://doi.org/10.1016/j.conb.2004.04.001
  34. Thoenen, H. 2000. Neurotrophins and activity-dependent plasticity. Prog. Brain Res. 128, 183-191. https://doi.org/10.1016/S0079-6123(00)28016-3
  35. Toldy, A., K. Stadler, M. Sasvári, J. Jakus, K. J. Jung, H. Y. Chung, I. Berkes, C. Nyakas, and Z. Radák. 2005. The effect of exercise and nettle supplementation on oxidative stress markers in the rat brain. Brain Res. Bull. 65, 487-493. https://doi.org/10.1016/j.brainresbull.2005.02.028
  36. Wirth, M. J., A. Brun, J. Grabert, S. Patz, and P. Wahle. 2003. Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5. Development 130, 5827-5838. https://doi.org/10.1242/dev.00826
  37. Yanagita, S., S. Amemiya, S. Suzuki, and I. Kita. 2007. Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats. Life Sci. 80, 356-363. https://doi.org/10.1016/j.lfs.2006.09.027
  38. Yu, Y., Q. Wang, and X. F. Huang. 2009. Energy-restricted pair-feeding normalizes low levels of brain-derived neurotrophic factor/tyrosine kinase B mRNA expression in the hippocampus, but not ventromedial hypothalamic nucleus, in diet-induced obese mice. Neuroscience 160, 295-306. https://doi.org/10.1016/j.neuroscience.2009.01.078
  39. Zheng, H., Y. F. Li, K. G. Cornish, I. H. Zucker, and K. P. Patel. 2005. Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure. Am. J. Physiol. Heart Circ. Physiol. 288, 2332-2341. https://doi.org/10.1152/ajpheart.00473.2004

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