進階搜尋


 
系統識別號 U0026-0812200912091868
論文名稱(中文) 急性運動對於小鼠不同腦區中BDNF和TrkB基因表現的影響
論文名稱(英文) Effects of acute exercise on BDNF and TrkB gene expression in mice different brain areas
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 94
學期 2
出版年 95
研究生(中文) 羅世豪
研究生(英文) Shih-Hao Luo
電子信箱 s3693104@mail.ncku.edu.tw
學號 s3693104
學位類別 碩士
語文別 英文
論文頁數 75頁
口試委員 口試委員-任卓穎
召集委員-黃阿敏
指導教授-陳洵瑛
中文關鍵字 小腦  皮質額葉  海馬迴  旋轉肌凝蛋白相關蛋白質激酶B  運動訓練  急性中度運動  急性劇烈運動  大腦衍生神經滋養因子 
英文關鍵字 exercise training  hippocampus  acute severe exercise  acute moderate exercise  BDNF  TrkB  frontal cortex  cerebellum 
學科別分類
中文摘要   急性運動可對身體功能引起許多暫時性的影響,例如內分泌及心血管系統等。然而,對於腦功能的影響就目前為止尚未清楚。大腦衍生神經滋養因子(BDNF),為神經滋養因子家族的一員,透過其受體-旋轉肌凝蛋白相關蛋白質激酶B(TrkB)扮演著調控神經可塑性的重要角色。過去的研究指出,BDNF及其受體TrkB的表現受到神經元活性所調控,而在我們過去的實驗中也指出,單一次的運動可以短暫的讓大鼠腦中海馬迴(hippocampus)中的BDNF蛋白表現量上升。在本實驗中,我們主要探討的是急性運動是否可以調控不同腦區中BDNF及其受體TrkB的表現。我們使用三個月大的小鼠(品系為C57BL/6,簡稱B6)做不同的運動方式:運動訓練四週、單一次的急性中度或劇烈運動,並在運動後不同時間點犠牲,取出其海馬迴、小腦(cerebellum)及皮質額葉(frontal cortex)來作蛋白質或mRNA的分析。我們的結果顯示,急性中度運動後,海馬迴中TrkB mRNA的表現量立即有顯著的增加,而蛋白質的表現則是在二到四小時後有明顯的上升。然而BDNF並未有顯著的改變。小腦則是在運動後立即觀察到全長型的TrkB蛋白(Full-length TrkB,TrkB.FL)有顯著性的上升,然而在皮質額葉則是都沒有變化。而訓練四週小鼠的海馬迴BDNF在最後一次運動後四小時則是有顯著上升,full-length TrkB則顯示了運動的慢性效果,然而這些蛋白在小腦及皮質額葉則都沒變化。這些結果已初步排除壓力或糖皮質激素的影響。相反的,急性劇烈運動後一小時則有降低TrkB蛋白表現的趨勢,但無顯著差異。這些結果指出,不同運動模式及腦區對於B6小鼠腦中BDNF及TrkB的調控有不同的影響,而這些改變對於生理上的意義仍有待進一步證實。

英文摘要   Acute exercise induces transient changes in our body function, such as endocrine and cardiovascular systems. Whether it influences the brain function is still unclear. Brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, plays an important role in neuroplasticity via its receptor – tropomyosin-related kinase B (TrkB). The expression of BDNF and its receptor TrkB is activity-dependent. It has been shown that a single bout of exercise acutely increases rat hippocampal BDNF protein level in our previous study. In this study, we want to further clarify if acute exercise can modulate BDNF and TrkB in different brain areas. To address this issue, male C57BL/6 mice (3-month-old) were subjected to different exercise protocols. i.e. 4 weeks moderate exercise training, a single bout of moderate or severe exercise, and were sacrificed at different time course after exercise. Hippocampus, cerebellum and frontal cortex were collected for the measurement of mRNA or protein expression. The results of mice experienced acute moderate exercise showed that hippocampal TrkB mRNA expression was increased immediately after exercise, and its protein expression was elevated 2 and 4 hours later. However, BDNF was not changed. Cerebellar full-length TrkB protein was increased immediately after exercise. There was no significant change of these two proteins in the frontal cortex. The exercise-trained mice increased their hippocampal BDNF 4 hours after the last run when compared to the control group, and TrkB expression was higher than control even two days after exercise training; however, there was no change of these two proteins in cerebellum or frontal cortex. These results may be independent of stress, because of the comparable levels of serum corticosterone among all studied groups except the 0-hr one. In contrast, acute severe exercise tended to decrease hippocampal expression of TrkB 1 hour after exercise. These results indicate a differential regulation of BDNF and TrkB by either different exercise regimes or in different brain areas after exercise in the brain of C57BL/6 mouse. The physiological significance of these changes needs to be further clarified.
論文目次 Abstract in Chinese…………………………………………………………………I
Abstract……………………………………………………………………………II
Acknowledgments…………………………………………………………………III
Table ofcontents…………………………………………………………………IV
List of Table………………………………………………………………………V
List of Figures……………………………………………………………………VI
List of Appendix………………………………………………………………VII
Introduction………………………………………………………………………1
Materials and Methods……………………………………………………………7
Results……………………………………………………………………………21
Discussion………………………………………………………………………25
Conclusion………………………………………………………………………31
References………………………………………………………………………32
Table………………………………………………………………………………39
Figures……………………………………………………………………………41
Appendix…………………………………………………………………………62
About the Author ………………………………………………………………75
參考文獻 1.Alonso M., Vianna M.R., Depino A.M., Mello e Souza T., Pereira P., Szapiro G., Viola H, Pitossi F., Izquierdo I., and Medina J.H. BDNF-triggered events in the rat hippocampus are required for both short- and long-term memory formation. Hippocampus 2002; 12:551-60.
2.Armanini M.P., McMahon S.B., Sutherland J., Shelton D.L., and Phillips H.S. Truncated and catalytic isoforms of trkB are co-expressed in neurons of rat and mouse CNS. Eur J Neurosci. 1995; 7:1403-9.
3.Baxter G.T., Radeke M.J., Kuo R.C., Makrides V., Hinkle B., Hoang R., Medina-Selby A., Coit D., Valenzuela P., Feinstein S.C. Signal transduction mediated by the truncated trkB receptor isoforms, trkB.T1 and trkB.T2. J Neurosci. 1997; 17:2683-90.
4.Berchtold N.C., Chinn G., Chou M., Kesslak J.P., and Cotman C.W. Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience 2005; 133:853-61.
5.Biffo S., Offenhauser N., Carter B.D., and Barde Y.A. Selective binding and internalisation by truncated receptors restrict the availability of BDNF during development. Development 1995; 121:2461-70.
6.Blum R. and Konnerth A. Neurotrophin-mediated rapid signaling in the central nervous system: mechanisms and functions. Physiology 2005; 20:70-8.
7.Black J.E., Greenough W.T., Anderson B.J., and Isaacs K.R. Environment and the aging brain. Can J Psychol. 1987; 41:111-30.
8.Barde Y.A., Edgar D., and Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982; 1:549-53.
9.Carro E., Nunez A., Busiguina S., and Torres-Aleman I. Circulating insulin-like growth factor I mediates effects of exercise on the brain. J Neurosci. 2000; 20:2926-33.
10.Carro E., Trejo J.L., Busiguina S., and Torres-Aleman I. Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J Neurosci. 2001; 21:5678-84.
11.Chodzko-Zajko W.J. and Moore K.A. Physical fitness and cognitive functioning in aging. Exerc Sport Sci Rev. 1994; 22:195-220.
12.Cotman C.W. and Engesser-Cesar C. Exercise enhances and protects brain function. Exerc Sport Sci Rev. 2002; 30:75-9.
13.Dragunow M., Hughes P., Mason-Parker S.E., Lawlor P., and Abraham W.C. TrkB expression in dentate granule cells is associated with a late phase of long-term potentiation. Brain Res Mol Brain Res. 1997; 46:274-80.
14.Du J., Feng L., Yang F., Lu B. Activity- and Ca2+-dependent modulation of surface expression of brain-derived neurotrophic factor receptors in hippocampal neurons.J Cell Biol. 2000; 150:1423-34.
15.Dugich-Djordjevic M.M., Ohsawa F., Okazaki T., Mori N., Day J.R., Beck K.D., and Hefti F. Differential regulation of catalytic and non-catalytic trkB messenger RNAs in the rat hippocampus following seizures induced by systemic administration of kainate. Neuroscience 1995; 66:861-77.
16.Dustman R.E., Ruhling R.O., Russell E.M., Shearer D.E., Bonekat H.W., Shigeoka J.W., Wood J.S., and Bradford D.C. Aerobic exercise training and improved neuropsychological function of older individuals. Neurobiol Aging 1984; 5:35-42.
17.Dustman R.E., Emmerson R.Y., Ruhling R.O., Shearer D.E., Steinhaus L.A., Johnson S.C., Bonekat H.W., and Shigeoka J.W. Age and fitness effects on EEG, ERPs, visual sensitivity, and cognition. Neurobiol Aging 1990; 11:193-200.
18.Eide F.F., Vining E.R., Eide B.L., Zang K., Wang X.Y., and Reichardt L.F. Naturally occurring truncated trkB receptors have dominant inhibitory effects on brain-derived neurotrophic factor signaling. J Neurosci. 1996; 16:3123-9.
19.Farmer J., Zhao X., van Praag H., Wodtke K., Gage F.H., and Christie B.R. Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 2004; 124:71-9.
20.Floeter M. K. and Greenough W.T. Cerebellar plasticity: modification of Purkinje cell structure by differential rearing in monkeys. Science 1979; 206:227-9.
21.Fryer R.H., Kaplan D.R., and Kromer L.F. Truncated trkB receptors on nonneuronal cells inhibit BDNF-induced neurite outgrowth in vitro. Exp Neurol. 1997; 148:616-27.
22.Gomez-Pinilla F., Dao L., and So V. Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Res. 1997; 764:1-8.
23.Gomez-Pinilla F., So V., and Kesslak J.P. Spatial learning and physical activity contribute to the induction of fibroblast growth factor: neural substrates for increased cognition associated with exercise. Neuroscience 1998; 85:53-61.
24.Haapasalo A., Koponen E., Hoppe E., Wong G., and Castren E. Truncated trkB.T1 is dominant negative inhibitor of trkB.TK+-mediated cell survival. Biochem Biophys Res Commun. 2001; 280:1352-8.
25.Huang A.M., Jen C.J., Chen H.F., Yu L., Kuo Y.M., and Chen H.I. Compulsive exercise acutely upregulates rat hippocampal brain-derived neurotrophic factor. J Neural Transm. 2006; 113:803-811.
26.Ickes B.R., Pham T.M., Sanders L.A., Albeck D.S., Mohammed A.H., and Granholm A.C. Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain. Exp Neurol. 2000; 164:45-52.
27.Kaplan D.R. and Miller F.D. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000; 10:381-91.
28.Klein R., Conway D., Parada L.F., and Barbacid M. The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain. Cell 1990; 61:647-56.
29.Klintsova A.Y., Dickson E., Yoshida R., and Greenough W.T. Altered expression of BDNF and its high-affinity receptor TrkB in response to complex motor learning and moderate exercise. Brain Res. 2004; 1028:92-104.
30.Korte M., Carroll P., Wolf E., Brem G., Thoenen H., and Bonhoeffer T. Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci U S A. 1995; 92:8856-60.
31.Korte M., Griesbeck O., Gravel C., Carroll P., Staiger V., Thoenen H., and Bonhoeffer T. Virus-mediated gene transfer into hippocampal CA1 region restores long-term potentiation in brain-derived neurotrophic factor mutant mice. Proc Natl Acad Sci U S A. 1996; 93:12547-52.
32.Lee T.H., Jang M.H., Shin M.C., Lim B.V., Kim Y.P., Kim H., Choi H.H., Lee K.S., Kim E.H., and Kim C.J. Dependence of rat hippocampal c-Fos expression on intensity and duration of exercise. Life Sci. 2003; 72:1421-36.
33.Leibrock J., Lottspeich F., Hohn A., Hofer M., Hengerer B., Masiakowski P., Thoenen H., and Barde Y.A. Molecular cloning and expression of brain-derived neurotrophic factor. Nature 1989; 341:149-52.
34.Lu B. BDNF and activity-dependent synaptic modulation. Learn Mem. 2003; 10:86-98.
35.Ma Y.L., Wang H.L., Wu H.C., Wei C.L., and Lee E.H. Brain-derived neurotrophic factor antisense oligonucleotide impairs memory retention and inhibits long-term potentiation in rats. Neuroscience 1998; 82:957-67.
36.Martinez J.L. Jr, and Derrick B.E. Long-term potentiation and learning. Annu Rev Psychol. 1996; 47:173-203.
37.Middlemas D.S., Lindberg R.A., and Hunter T. trkB, a neural receptor protein- tyrosine kinase: evidence for a full-length and two truncated receptors. Mol Cell Biol. 1991; 11: 143–153.
38.Molteni R, Ying Z, and Gomez-Pinilla F. Differential effects of acute and chronic exercise on plasticity- related genes in the rat hippocampus revealed by microarray. Eur J Neurosci. 2002; 16:1107-16.
39.Mizuno M., Yamada K., Takei N., Tran M.H., He J., Nakajima A., Nawa H., and Nabeshima T. Phosphatidylinositol 3-kinase: a molecule mediating BDNF- dependent spatial memory formation. Mol Psychiatry 2003; 8:217-24.
40.Mu J.S., Li W.P., Yao Z.B., and Zhou X.F. Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats. Brain Res. 1999; 835: 259 -65.
41.Nagappan G. and Lu B. Activity-dependent modulation of the BDNF receptor TrkB: mechanisms and implications. Trends Neurosci. 2005; 28:464-71.
42.Neeper S.A., Gomez-Pinilla F., Choi J., and Cotman C. Exercise and brain neurotrophins. Nature 1995; 373:109.
43.Neeper S.A., Gomez-Pinilla F., Choi J., Cotman C.W. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 1996; 726:49-56.
44.Nibuya M., Takahashi M., Russell D.S., and Duman R.S. Repeated stress increases catalytic TrkB mRNA in rat hippocampus. Neurosci Lett. 1999; 267:81-4.
45.Oliff H.S., Berchtold N.C., Isackson P., and Cotman C.W. Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus. Brain Res Mol Brain Res. 1998; 61: 147-53.
46.Pysh J. J. and Weiss G.M. Exercise during development induces and increases in Purkinje cell dendritic tree size. Science 1979; 206:230-2.
47.Radak Z., Kaneko T., Tahara S., Nakamoto H., Pucsok J., Sasvari M., Nyakas C., and Goto S. Regular exercise improves cognitive function and decreases oxidative damage in rat brain. Neurochem Int. 2001; 38:17-23.
48.Rose C.R., Blum R., Pichler B., Lepier A., Kafitz K.W., and Konnerth A. Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells. Nature 2003; 426:74-8.
49.Rudge J.S., Li Y., Pasnikowski E.M., Mattsson K., Pan L., Yancopoulos G.D., Wiegand S.J., Lindsay R.M., and Ip N.Y. Neurotrophic factor receptors and their signal transduction capabilities in rat astrocytes. Eur J Neurosci. 1994; 6:693-705.
50.Schaaf M.J., Hoetelmans R.W., de Kloet E.R., and Vreugdenhil E. Corticosterone regulates expression of BDNF and trkB but not NT-3 and trkC mRNA in the rat hippocampus. J Neurosci Res. 1997; 48:334-41.
51.Srere P.A. Citrate synthase. Methods Enzymol. 1969; 13:3-5.
52.Smith M.A., Makino S., Kvetnansky R., and Post R.M. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci. 1995; 15:1768-77.
53.Soppet D., Escandon E., Maragos J., Middlemas D.S., Reid S.W., Blair J., Burton L.E., Stanton B.R., Kaplan D.R., and Hunter T. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell 1991; 65:895-903.
54.Spirduso W.W. Physical fitness, aging, and psychomotor speed: a review. J Gerontol. 1980; 35:850-65.
55.Squinto S.P., Stitt T.N., Aldrich T.H., Davis S., Bianco S.M., Radziejewski C., Glass D.J., Masiakowski P., Furth M.E., and Valenzuela D.M. trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell 1991; 65:885-93.
56.Su S.H., Chen H.I. and Jen C.J. C57BL/6 and BALB/c bronchoalveolar macrophages respond differently to exercise. J Immunol. 2001; 167:5084-91.
57.Suzuki S., Numakawa T., Shimazu K., Koshimizu H., Hara T., Hatanaka H., Mei L., Lu B., Kojima M. BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts: roles in synaptic modulation. J Cell Biol. 2004; 167:1205-15.
58.Tong L., Shen H., Perreau V.M., Balazs R., and Cotman C.W. Effects of exercise on Gene-Expression Profile in the Rat Hippocampus. Neurobiol Dis. 2001; 8:1046-56.
59.Tongiorgi E., Righi M., Cattaneo A. Activity-dependent dendritic targeting of BDNF and TrkB mRNAs in hippocampal neurons. J Neurosci. 1997; 17:9492-505.
60.van Praag H., Christie B.R., Sejnowski T.J., and Gage F.H. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999; 96:13427-31.
61.Vaynman S., Ying Z., and Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci. 2004; 20:2580-90.
62.Yacoubian T.A. and Lo D.C. Truncated and full-length TrkB receptors regulate distinct modes of dendritic growth. Nat Neurosci. 2000; 3:342-9.

論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2007-08-25起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2009-08-25起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw