跳到主要內容

臺灣博碩士論文加值系統

(34.226.244.254) 您好!臺灣時間:2021/08/03 02:09
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:蘇建州
研究生(外文):Chien-ChouSu
論文名稱:壓力誘發腦中微膠細胞之活性
論文名稱(外文):Stress induces microglial activation in brain
指導教授:游一龍游一龍引用關係
指導教授(外文):Lung Yu
學位類別:碩士
校院名稱:國立成功大學
系所名稱:行為醫學研究所
學門:社會及行為科學學門
學類:心理學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:英文
論文頁數:44
中文關鍵詞:社交挫敗壓力微膠細胞中間前額葉海馬齒狀回脂多醣
外文關鍵詞:social defeat stressmicrogliamedial prefrontal cortexdentate gyruslipopolysaccharide
相關次數:
  • 被引用被引用:0
  • 點閱點閱:130
  • 評分評分:
  • 下載下載:7
  • 收藏至我的研究室書目清單書目收藏:0
長期心理壓力會造成個體在心理和生理上的負面影響。當個體遭受到壓力的時候,為了因應這些壓力源,身體會產生因應這些壓力的反應,這時大腦會活化交感神經系統和神經內分系統,刺激腎上腺分泌腎上腺素、正腎上腺素和葡萄糖皮質素,這些分泌出來的物質,會促使醣類、蛋白質和脂質,轉換成可利用的能量,並且產生戰或逃的反應。短期而言,葡萄糖皮質素對於個體因壓力是有幫助的,但長期而言,體內具有高濃度的葡萄糖皮質素對身體是具有傷害的。在臨床上,長期心理壓力是造成重鬱症的危險因子之一,而患有重鬱症的病人,其血液裡有較高濃度的介白素-1(interleukin-1)、介白素-6(interleukin-6)和腫瘤壞死因子α(tumor necrosis factor α),這些前發炎性細胞激素(proinflammatory cytokine)和大腦中微膠細胞(microglia)的活化是否有關連,目前尚未清楚。因此我們假設長期心理壓力會誘發微膠細胞的活化,以及輕微感染會加強長期心理壓力對微膠細胞的活性,尤其是對壓力較為敏感的腦區:中間前額葉和海馬齒狀回(dentate gyrus),並利用社交挫敗(social defeat)的動物模式去模擬長期心理壓力。結果顯示小鼠經歷過連續十天的社交挫敗壓力後,在社交易感性(susceptible)和社交恢復力(resilient)的小鼠,其中間前額葉海和海馬齒狀回區域,微膠細胞增加的數量並沒有組間差異。接著我們利用較低劑量的脂多醣(lipopolysaccharide, LPS) (0.125mg/kg),透過周邊給予的方式,模擬輕微感染的狀況,並且檢驗是否經歷社交挫敗壓力又伴隨輕微感染時,會加強微膠細胞的活化程度。另外我們也使用行為實驗去測量動物在經歷過不同實驗處理後,其短期記憶和工作記憶上的表現。結果指出社交易感性且施打LPS的小鼠,在海馬齒狀回區域,會顯著地增加微膠細胞的數量;但是在中間前額葉的區域,其微膠細胞增加的數量並不顯著。而行為上,社交易感性且有LPS處理的小鼠,在物體再認測驗(object recognition test)和Y迷津(Y maze)的再認測驗(recognition test)中,其表現水準皆比其他組別的小鼠來的低。因此本研究的結果顯示,長期經歷社交挫敗壓力又伴隨輕微感染時,實驗動物在認知上會造成短期記憶的受損,並且會加強在海馬齒狀回區域的微膠細胞之活性。
Chronic psychological stress has negative effects on mental and physical well-being. In response to stress, the brain activates the sympathetic nervous system and neuroendocrine system to release epinephrine, norepinephrine and glucocorticoids. These stressor-induced pathways have a profound influence on behavior and physiology in humans. In clinic, chronic psychological stress is one of the critical risk factors in the emergence of major depression. Previous studies indicated that interleukin-1, interleukin-6 and tumor necrosis factor α are increased in the peripheral blood of acutely depressed patients. It is unclear whether these changes are associated with microglial activation in the brain. Therefore, we hypothesize that chronic psychological stress induces microglial activation and slight infection facilitates effects of chronic psychological stress on microglial activation in the medial prefrontal cortex and dentate gyrus. Here, we show that chronic social defeat stress did not increase number of Iba1 positive cells on defeat susceptible and defeat resilient mice in the medial prefrontal cortex and dentate gyrus that are susceptibility to stress. We then used low dose of LPS (0.125mg/kg) as slight infection and examined whether chronic social defeat stress plus low dose of LPS potentiated microglial activation. We also investigated the effects of microglial activation on the short-term memory and the working memory. The results showed that the number of Iba1 positive cells was significantly higher in defeat susceptible group treated with LPS in dentate gyrus but there was not a significant difference between means of four groups in medial prefrontal cortex. Defeat susceptible group treated with LPS also displayed deteriorated recognition performance in object recognition test and significantly spent less time in exploring the unfamiliar arm in recognition test of Y maze. Thus, the mice treated with chronic social defeat stress plus low dose of LPS exhibited impaired short-term memory and potentiated microglial activation in the dentate gyrus.
Abstract (Chinese)……………………………………………1-2
Abstract (English)……………………………………………3-4
Introduction……………………………………………………………9-12
Material and methods………………………………………13-18
Animals………………………………………………………………13
Behavioral procedures…………………………13-15
Drugs……………………………………………………………………16
Immunohistochemistry……………………………16-17
Experimental design………………………………17
Data analysis and statistics………18
Results…………………………………………………………………………19-21
Discussion…………………………………………………………………22-23
References…………………………………………………………………24-28

Aguilera, G. (1994). Regulation of pituitary ACTH secretion during chronic stress. [Review]. Front Neuroendocrinol, 15(4), 321-350.

Barron, K. D. (1995). The microglial cell. A historical review. [Historical Article
Research Support, U.S. Gov't, Non-P.H.S.
Review]. J Neurol Sci, 134 Suppl, 57-68.

Berton, O., McClung, C. A., Dileone, R. J., Krishnan, V., Renthal, W., Russo, S. J., et al. (2006). Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. [Research Support, Non-U.S. Gov't]. Science, 311(5762), 864-868.

Carlson, N. R. (2010). Physiology of behavior (10th ed.). Boston: Allyn & Bacon.

Cherng, C. F., Chang, C. P., Su, C. C., Tzeng, W. Y., Chuang, J. Y., Chen, L. H., et al. (2012). Odors from proximal species reverse the stress-decreased neurogenesis via main olfactory processing. Behav Brain Res, 229(1), 106-112.

Cuadros, M. A., & Navascues, J. (1998). The origin and differentiation of microglial cells during development. [Research Support, Non-U.S. Gov't
Review]. Prog Neurobiol, 56(2), 173-189.

Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. [Research Support, N.I.H., Extramural
Review]. Nat Rev Neurosci, 9(1), 46-56.

de Kloet, E. R., Joels, M., & Holsboer, F. (2005). Stress and the brain: from adaptation to disease. [Research Support, Non-U.S. Gov't
Review]. Nat Rev Neurosci, 6(6), 463-475.

Fox, S. I. (2008). Human physiology (10th ed.). Dubuque, IA: McGraw-Hill.

Gould, E., Tanapat, P., McEwen, B. S., Flugge, G., & Fuchs, E. (1998). Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. [Research Support, U.S. Gov't, P.H.S.]. Proc Natl Acad Sci U S A, 95(6), 3168-3171.

Graeber, M. B. (2010). Changing face of microglia. [Review]. Science, 330(6005), 783-788.

Hammen, C. (2005). Stress and depression. [Review]. Annu Rev Clin Psychol, 1, 293-319.

Hanisch, U. K., & Kettenmann, H. (2007). Microglia: active sensor and versatile effector cells in the normal and pathologic brain. [Research Support, Non-U.S. Gov't
Review]. Nat Neurosci, 10(11), 1387-1394.

Herman, J. P., Ostrander, M. M., Mueller, N. K., & Figueiredo, H. (2005). Limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocortical axis. [Research Support, N.I.H., Extramural
Review]. Prog Neuropsychopharmacol Biol Psychiatry, 29(8), 1201-1213.

Hyman, S. E. (2007). How mice cope with stressful social situations. [Comment]. Cell, 131(2), 232-234.

Imai, Y., & Kohsaka, S. (2002). Intracellular signaling in M-CSF-induced microglia activation: role of Iba1. [Research Support, Non-U.S. Gov't
Review]. Glia, 40(2), 164-174.

Ito, D., Imai, Y., Ohsawa, K., Nakajima, K., Fukuuchi, Y., & Kohsaka, S. (1998). Microglia-specific localisation of a novel calcium binding protein, Iba1. [Research Support, Non-U.S. Gov't]. Brain Res Mol Brain Res, 57(1), 1-9.

Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1999). Causal relationship between stressful life events and the onset of major depression. [Research Support, U.S. Gov't, P.H.S.
Twin Study]. Am J Psychiatry, 156(6), 837-841.

Kitamura, Y., Yanagisawa, D., Inden, M., Takata, K., Tsuchiya, D., Kawasaki, T., et al. (2005). Recovery of focal brain ischemia-induced behavioral dysfunction by intracerebroventricular injection of microglia. [Comparative Study
Research Support, Non-U.S. Gov't]. J Pharmacol Sci, 97(2), 289-293.

Klegeris, A., McGeer, E. G., & McGeer, P. L. (2007). Therapeutic approaches to inflammation in neurodegenerative disease. [Research Support, Non-U.S. Gov't
Review]. Curr Opin Neurol, 20(3), 351-357.

Lagace, D. C., Donovan, M. H., DeCarolis, N. A., Farnbauch, L. A., Malhotra, S., Berton, O., et al. (2010). Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance. [Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.]. Proc Natl Acad Sci U S A, 107(9), 4436-4441.

Liu, B., & Hong, J. S. (2003). Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. [Review]. J Pharmacol Exp Ther, 304(1), 1-7.

McEwen, B. S. (1998). Stress, adaptation, and disease. Allostasis and allostatic load. [Review]. Ann N Y Acad Sci, 840, 33-44.

Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. [Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
Review]. Biol Psychiatry, 65(9), 732-741.

Nestler, E. J., & Hyman, S. E. (2010). Animal models of neuropsychiatric disorders. [Review]. Nat Neurosci, 13(10), 1161-1169.

Paxinos, G., & Franklin, K. B. J. (2001). The mouse brain in stereotaxic coordinates (2nd ed.). San Diego, Calif. ; London: Academic.

Qin, L., Wu, X., Block, M. L., Liu, Y., Breese, G. R., Hong, J. S., et al. (2007). Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. [Comparative Study
Research Support, N.I.H., Extramural]. Glia, 55(5), 453-462.

Radley, J. J., Rocher, A. B., Miller, M., Janssen, W. G., Liston, C., Hof, P. R., et al. (2006). Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. [Research Support, N.I.H., Extramural]. Cereb Cortex, 16(3), 313-320.

Ransohoff, R. M., & Cardona, A. E. (2010). The myeloid cells of the central nervous system parenchyma. [Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review]. Nature, 468(7321), 253-262.

Rosenkranz, J. A., Venheim, E. R., & Padival, M. (2010). Chronic stress causes amygdala hyperexcitability in rodents. [Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't]. Biol Psychiatry, 67(12), 1128-1136.

Tanaka, S., Ide, M., Shibutani, T., Ohtaki, H., Numazawa, S., Shioda, S., et al. (2006). Lipopolysaccharide-induced microglial activation induces learning and memory deficits without neuronal cell death in rats. [Research Support, Non-U.S. Gov't]. J Neurosci Res, 83(4), 557-566.

Ulrich-Lai, Y. M., & Herman, J. P. (2009). Neural regulation of endocrine and autonomic stress responses. [Research Support, N.I.H., Extramural
Review]. Nat Rev Neurosci, 10(6), 397-409.

Uno, H., Tarara, R., Else, J. G., Suleman, M. A., & Sapolsky, R. M. (1989). Hippocampal damage associated with prolonged and fatal stress in primates. [Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.]. J Neurosci, 9(5), 1705-1711.

Vyas, A., Mitra, R., Shankaranarayana Rao, B. S., & Chattarji, S. (2002). Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. [Research Support, Non-U.S. Gov't]. J Neurosci, 22(15), 6810-6818.

Wu, C. W., Chen, Y. C., Yu, L., Chen, H. I., Jen, C. J., Huang, A. M., et al. (2007). Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory. [Research Support, Non-U.S. Gov't]. J Neurochem, 103(6), 2471-2481.

Wu, S. Y., Wang, T. F., Yu, L., Jen, C. J., Chuang, J. I., Wu, F. S., et al. (2011). Running exercise protects the substantia nigra dopaminergic neurons against inflammation-induced degeneration via the activation of BDNF signaling pathway. [Research Support, Non-U.S. Gov't]. Brain Behav Immun, 25(1), 135-146.

Zorrilla, E. P., Luborsky, L., McKay, J. R., Rosenthal, R., Houldin, A., Tax, A., et al. (2001). The relationship of depression and stressors to immunological assays: a meta-analytic review. [Meta-Analysis
Research Support, U.S. Gov't, P.H.S.]. Brain Behav Immun, 15(3), 199-226.

連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊