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系統識別號 U0026-0802201217171300
論文名稱(中文) BDNF-TrkB訊息路徑在跑步機運動訓練對大白鼠杏仁體側核長期增益現象之增強作用中所扮演的角色
論文名稱(英文) The Role of the BDNF-TrkB Pathway in Treadmill Exercise-Induced Enhancement of Long-Term Potentiation in the Rat Lateral Amygdala
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 100
學期 1
出版年 101
研究生(中文) 劉智璿
研究生(英文) Chih-Hsuan Liu
學號 s36984042
學位類別 碩士
語文別 英文
論文頁數 52頁
口試委員 指導教授-吳豐森
召集委員-黃阿敏
口試委員-游一龍
中文關鍵字 腦源性神經滋養分子  杏仁體側核  長期增益現象  被動迴避記憶  磷酸肌醇-3激酶  磷酸激脢C  磷脂酶C  跑步機運動訓練  TrkB受體 
英文關鍵字 BDNF  Lateral amygdala  Long-term potentiaiton  Passive avoidance memory  PI3K  PKC  PLC  Treadmill exercise  TrkB receptor 
學科別分類
中文摘要 長期增益現象(LTP)是當突觸前神經纖維受到高頻電刺激(HFS)後,突觸間興奮性訊息傳導效率持續性增強的一種現象。HFS所誘發的LTP目前被認為是腦中處理學習和記憶的一種基本細胞模式。先前的研究報告指出,跑步機運動訓練會藉由抑制老鼠杏仁體與海馬迴之血清素1A(5-HT1A)受體的活化,以及增加此二腦區腦源性神經滋養因子(BDNF)及其受體TrkB的表現,來促進動物被動迴避試驗(一種與杏仁體和海馬區域密切相關之聯結性記憶測試)的學習與記憶能力。最近我們實驗室的研究進一步發現,跑步機運動可藉由降低5-HT1A受體的活化,來增強大白鼠杏仁體側核(LA)及海馬齒狀迴(DG)區域HFS所誘發的LTP。但是跑步機運動訓練是否亦可透過活化BDNF-TrkB訊息路徑,來增強LA-LTP和DG-LTP,則不得而知。因此在本研究中,我們利用胞外電生理紀錄的技術及藥理學的方法,首先探討BDNF-TrkB路徑在運動訓練增強雄性大白鼠LA-LTP的作用中所扮演的角色。我們的結果顯示,四週跑步機運動訓練可顯著增強雄性大白鼠HFS所誘發的LA-LTP。我們也發現,施予K252a (一種TrkB受體拮抗劑)可阻斷運動訓練對LA-LTP的增強作用,表示BDNF-TrkB路徑有參與運動訓練對LA-LTP的增強作用。此外,分別給予U73122(磷脂酶C抑制劑)、Bis 1(磷酸激酶C抑制劑)或wortmannin(磷酸肌醇3-激酶抑制劑),都可消除運動訓練對LA-LTP的增強作用,顯示運動訓練是藉由活化BDNF-TrkB路徑下游的這些訊息傳遞分子來增強LA-LTP。相反地,給予PD98059 (MEK抑制劑)去阻斷MAPK路徑,則不會影響運動訓練對LA-LTP的增強作用。綜合上述結果,我們的研究顯示,BDNF-TrkB訊息路徑及其下游的訊息傳遞分子包括磷脂酶C、磷酸激脢C和磷酸肌醇3-激酶皆有參與跑步機運動訓練對雄性大白鼠HFS所誘發LA-LTP的增強作用。
英文摘要 Long-term potentiation (LTP) is a phenomenon in which brief high-frequency stimulation (HFS) of a synaptic pathway results in long-term enhancement of efficacy of connections made by that pathway. LTP is considered as a possible basis for learning and memory in the brain. Previous studies have demonstrated that treadmill exercise enhances passive avoidance (PA) memory via attenuating the activation of serotonin type 1A (5-HT1A) receptors and upregulating levels of brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) in the rodent hippocampus and amygdala, brain areas highly associated with PA learning. Recent studies form our laboratory have further indicated that exercise facilitates HFS-induced LTP in the rat hippocampal detate gyrus (DG) and lateral amygdala (LA) via reducing 5-HT1A receptor activation. However, it is unclear whether the BDNF-TrkB pathway is also involved in exercise-induced enhancement of LA- and DG-LTP. In the present study, we thus initially determined the role of the BDNF-TrkB pathway in exercise-induced enhancement of LA-LTP in male rats by use of the extracellular electrophysiological recording technique and pharmacological methods. Our results revealed that four-week treadmill exercise enhanced HFS-induced LA-LTP in male rat slices. In addition, bath perfusion of the TrkB inhibitor K252a abolished exercise-induced enhancement of LA-LTP, suggesting that the BDNF-TrkB pathway was involved in the promoting effect of exercise. Moreover, exercise-induced enhancement of LA-LTP was completely reversed by the phospholipase C (PLC inhibitor U73122, the protein kinase C (PKC) inhibitor Bis I, or the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin, indicating that exercise acted through PLC, PKC, and PI3K to potentiate LA-LTP. In contrast, using the MEK inhibitor PD98059 to block the MAPK pathway has little effect on exercise-induced enhancement of LA-LTP. In summary, our studies demonstrate that the BDNF-TrkB pathway and its downstream signaling molecules incuding PLC, PKC, and PI3K are involved in treadmill exercise-induced enhancement of LA-LTP in male rats.
論文目次 Abstract in Chinese……………………………………………………...I
Abstract………………………………………………………………...III
Table of Contents……………………………………………………….V
List of Figures........................................................................................VII
Abbreviations…………………………………………………………..IX
Introduction……………………………………………………………..1
Exercise alters central nerve system functions and synaptic plasticity………….1
Role of brain-derived neurotrophic factor (BDNF) in neuronal plasticity and memory…………………………………………………………………………..2
Effect of exercise on BDNF and TrkB expression levels………………………....5
Rationale and specific aims of this study………………………………………...6
Materials and Methods…………………………………………………7
Animals………………………………………………………………………….7
Treadmill exercise protocol………………………………………………………7
Slice preparation…………………………………………………………...…….7
Extracellular electrophysiological recordings.......................................................8
Drugs and chemicals……………………………………………………………..9
Statistical analysis…………………………………………..……………………9
Experimental Design……………………………………………………………..9
Results…………………………………………………………….…….12
Four-week treadmill exercise enhances HFS-induced LA-LTP.……………..…12
Bath perfusion of K252a abolishes exercise-induced enhancement of LA-LTP……………………………………………………………………….…12
Bath perfusion of U73122 abolishes exercise-induced enhancement of LA-LTP………………………………………………………………………….13
Bath perfusion of Bis I abolishes exercise-induced enhancement of LA-LTP……………………………………………………………………...…..13
Bath perfusion of wortmannin abolishes exercise-induced enhancement of LA-LTP.................................................................................................................14
Bath perfusion of PD98059 abolishes exercise-induced enhancement of LA-LTP………………………………………………………….………………14
Discussion……………………………..………………………………..16
Four-week treadmill training potentiates LA-LTP thorough BDNF-TrkB signaling transduction…………………………………………………………..16
Role of PLC and calcium signal in treadmill exercise-induced LA-LTP enhancement…………………………………………………………………….19
Role of PI3K-Akt and MAPK pathway in treadmill exercise-induced LA-LTP enhancement…………………………………………………………………….21
Conclusion……………………………………………………...………23
References…………………………………..…………………………..36
About the Author……………………...……………………………….52
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