大鼠血壓胺神經網路異常對自主神經功能及延腦心臟迷走神經元活性之影響

2009-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/692919摘要：本計畫將以三年時間，採用SSRI (citalopram)處理大鼠(SSRI-treated rats)為血壓胺(5-HT)神經網路異常模式動物，探討血壓胺神經網路異常，對調控心肺自主神經功能及延腦心臟迷走神經元活性之影響。第一年將檢測SSRI 處理動物的5-HT 系統，並進行SSRI處理時機與劑量-反應實驗：將以免疫組織化學技術，進行5-HT 系統之免疫標定(如：TPH, 5-HT, 5-HTT)，比較各個SSRI 處理組與控制組的5-HT 系統。並決定藥物處理的關鍵期與適當劑量。第二年將探討SSRI 處理動物自主神經功能與運動活性的變化：在大鼠神經發育的關鍵期(第一年的實驗結果)以SSRI 處理動物後，在P20-28 或成鼠時期，進行實驗組與控制組動物的自主神經功能與運動活性評估。注意清醒與睡眠時期自主神經功能的差異。隨後犧牲動物，進行5-HT 系統之免疫組織化學染色與分析，將注意有無性別差異存在。第三年將探討SSRI 處理動物心臟迷走神經元之抑制性及興奮性突觸傳導(IPSCs or EPSCs)是否發生改變。將以螢光逆向追蹤劑標定延腦疑核處的心臟迷走神經元後，以腦薄片(brain slice)電生理記錄方式，對大鼠之CVN 進行GABAergic IPSCs 與glutamatergic EPSCs 特徵之記錄與分析。將注意SSRI 動物是否產生長期GABA突觸傳導減弱之現象，並評估是否與5-HT2 接受器有關。實驗結果可為嬰兒猝死症(sudden infant death syndrome)提供一可能的神經化學機制。<br> Abstract: In the present three-year project, we use SSRI (selective serotonin reuptake inhibitors)-treated rats as animal model to investigate the effects of serotonergic abnormalities on the autonomic function and medullary cardiac vagal neuronal activity. In the first year, we will examine the serotonin circuitry of SSRI-treated animals to determine whether there exists a dose- and time- dependency in the effects of early SSRI exposure. We will evaluate the expression of TPH (tryptophan hydroxylase) or 5-HT (serotonin) in various raphe nuclei and the expression of 5-HT or 5-HTT (serotonin transporter) in axon terminals in cortex and brainstem with fluorescence immunohistochemistry. In the second year, we will evaluate the autonomic functions and the locomotor activity of the SSRI-treated animals. We will determine the relationship of early SSRI exposure on the physiological functions to that for TPH, 5-HT and 5-HTT expressions. In the third year, we will evaluate the inhibitory and excitatory neurotransmissions on the retrogradely rhodamine-labeled cardiac vagal neurons with whole cell patch recording in medullary brain slice of the SSRI-treated and control animals. We will determine whether there exist a long-lasting withdrawal of GABAergic neurotransmission and facilitation of glutamatergic excitatory input in SSRI-treated rats. We will also investigate the relative contribution of different 5-HT2 receptor subtypes. The results may provide a potential neurochemical mechanism that may be important in sudden infant death syndrome.血壓胺自主神經功能心臟迷走神經元大鼠SSRIserotoninautonomic functioncardiac vagal neuronrat大鼠血壓胺神經網路異常對自主神經功能及延腦心臟迷走神經元活性之影響