副交感神經

• 系統編號 RN9406-0583

• 計畫中文名稱 肥胖相關 Peptides 對大鼠迷走運動神經核之神經細胞的影響(III)

• 計畫英文名稱 Effects of Obesity-Related Peptides on Neurons of Dorsal Motor Nucleus of the Vagus in Rats (III)

• 主管機關 行政院國家科學委員會 • 計畫編號 NSC92-2320-B038-014

• 執行機構 臺北醫學大學醫學系

• 本期期間 9208 ~ 9307

• 報告頁數 9 頁 • 使用語言 英文

• 研究人員 黃玲玲 --

• 中文關鍵字 肥胖; 胜; 能量衡定; 背運動核; 神經張力素; 電生理; 副交感神經; 觸感痛; 脊髓; 蜘蛛膜下腔

• 英文關鍵字 Obesity; Peptide; Energy homeostasis; Dorsal motor nucleus of vagus; Neurotensin; Electrophysiology; Parasympathetic nerve;

Allodynia; Spinal cord; Intrathecal

• 中文摘要

肥胖是危害健康的一個危險因子, 肥胖人口比例不斷增加已使得肥胖成為包括台灣 在內的世界性公共健康問題。 近年來, 許多學者致力於尋找內生性肥胖相關物質以及其所扮演的生理角色與作用機制, 迄今, 已有一系列相關分子被發現, 下視丘 被認為是重要的 中樞能量衡定中心,至於那些中樞神經結構參與這些肥胖相關分子的作用仍需進一步的研究與探討。研究證 據顯示迷走運動神經核也可能是這些肥胖相關分子在中樞神經系統的作 用位置, 本計畫主持人提出一個假說, 認為迷走運 動神經核可能做為傳遞中樞神經系統之內生性肥胖相關物質的訊息到周邊組織器官的傳訊結構, 本計畫之目的即為探討內 生性肥胖相關物質對位於迷走運動神經核之副交感神經節前神經細胞的活性調節與其作用機制, 並藉以了解內生性肥胖相 關物質的生理角色以及迷走運動神經核在能量衡定系統中所扮演的角色。研究結果發現 orexin A, orexin B 以及 neurotensin 會使迷走運動神經核之神經細胞的細胞膜去極化, orexins 的離子作用機制為降低鉀離子通透性與同時增加鈉離子通透性,至 於 neurotensin 之離子作用機制則為降低鉀離子通透性。另外，我們亦測試 neuropeptide Y 在此核區的作用,但未測得任何 活性。這些結果提供證據支持本計畫的主要假說，並進一步了解這些受測之內生性肥胖相關物質在迷走運動神經核神經細 胞之作用機轉。已知的解剖及功能研究令我們相信 orexins 可能參與調節在脊髓層面的痛覺傳遞機制，因此我們亦在此計 畫中測試這個想法，我們發現 orexins 具有降低手術後之觸感痛現象 (allodynia)，且證實內生性 orexin A 可能在手術後被 釋放並作用於脊髓背根之 orexin 1receptor 產生降低觸感痛現象之作用。

• 英文摘要

Obesity is a serious threat to health and is now one of the major public health problems in the world and an emerging health problem in Taiwan. Extensive research efforts have focused on the discovery of obesity-related endogenous molecules, their physiological roles and underlying mechanism of actions. A panel of relevant molecules has been discovered. Although the hypothalamus seems to be an important target of many obesity-related molecules to exert their effects in regulating energy homeostasis, their subsequent central neuronal circuits still remain to be verified. Functional and anatomical studies imply the dorsal motor nucleus of the vagus (DMNV) and spinal dorsal horn as relay structures to transmit messages from the central nervous system to the peripheral organs for several energy balance-related molecules, such as orexins, leptin and neurotensin. Therefore, the principal investigator hereby

examined the effects of orexins, neuropeptide Y, leptin and neurotensin in these hypothesized relay structures. The physiological roles of obesity-related signaling molecules in regulation of the activities of parasympathetic preganglionic neurons in the rat DMNV and the underlying mechanisms were explored by means of electrophysiological approaches. In the present study, we found that orexin A, orexin B and neurotensin exhibited an excitatory effect, membrane depolarization, on DMNV neurons including the parasympathetic preganglionic neurons in the nucleus while no detectable effects of neuropeptide Y was found. The ionic mechanisms of orexins-induced depolarization were a combined non-selective cation conductance increase and potassium conductance decrease, whereas a decrease of potassium conductance is the major ionic mechanism of neurotensin-induced

membrane depolarization. These findings support the hypothesis that DMNV may serve as a relay structure for the obesity-related signaling molecules to transmit messages from the central nervous system to the peripheral organs as proposed by the principal investigator. They also provide a direct evidence for the cellular mechanism of these obesity-related neuropeptides in DMNV neurons. The involvement of orexins in the nociceptive sensory transmission at the spinal level is implicated by anatomical and electrophysiological studies. We, therefore, examined the anti-allodynic effect of orexins applied intrathecally in a rat model of postoperative pain. Intrathecal orexins were found to attenuate incision-induced allodynic response through orexin 1 receptors (OX1R). Orexin A antibody and OX1R antagonist SB-334867, but not orexin B antibody, intensified the incision-induced allodynic response, implicating that endogenous orexin A released after paw incision activates the OX1R in the spinal cord as an

anti-nociceptive protector.