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Central orexin-A inhibits reflex swallowing via caudal brainstem

中枢食欲素-A 通过尾部脑干抑制反射性吞咽

基本信息

批准号：
22592064
负责人：
KOBASHI Motoi
金额：
$ 2.91万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

We examined the effects of orexins on the reflex swallowing using anaesthetized rats. Orexins were administered into the fourth ventricle. Swallowing was induced by repeated electrical stimulation of the central cut end of the superior laryngeal nerve (SLN) and was identified by the electromyogram lead penetrated the mylohyoide muscle through bipolar electrodes. The frequency of swallowing during the electrical stimulation of the SLN decreased after the administration of orexin-A in a dose-dependent manner. The latency of the first swallowing tended to be extended after the administration of orexin-A. The administration of orexin-B did not affect swallowing frequency. Pre-administration of SB334867, an orexin1 receptor antagonist, attenuated the degree of inhibition of swallowing frequency induced by the administration of orexin-A. To identify the effective site of orexin-A, the effect of a microinjection of orexin-A into the dorsal vagal complex (DVC) was evaluated. Orexin-A was injected into one of the lateral DVC, the intermediate DVC, or the medial DVC. Microinjection of orexin-A into the medial DVC but not the other two sites decreased swallowing frequency. Pre-injection of SB334867 into the medial DVC disrupted the inhibitory response induced by fourth ventricular administration of orexin-A. The electrical lesion of the commissural part of the NTS, but not ablation of the AP, abolished the inhibition of reflex swallowing induced by fourth ventricular administration of orexin-A. These results suggest that orexin-A inhibits reflex swallowing via orexin1 receptors situated in the commissural part of the NTS and/or its vicinity.

我们利用麻醉大鼠观察了食欲素对反射性吞咽的影响。将食欲素注入第四脑室。反复电刺激喉上神经中央切断端(SLN)诱发吞咽，并通过双极电极引导肌电导联穿透肌舌肌识别吞咽。给予食欲素-A后，电刺激SLN时吞咽次数减少，且呈剂量依赖关系。首次吞咽潜伏期在给予食欲素-A后有延长的趋势。给予食欲素-B并不影响吞咽频率。预先给予食欲素-1受体拮抗剂SB334867可减轻食欲素-A对吞咽频率的抑制程度。为了确定食欲素-A的作用部位，我们观察了迷走神经背侧复合体(DVC)微量注射食欲素-A的作用。将增食欲素-A注射到DVC的外侧、中间或内侧。DVC内侧区微量注射食欲素-A，但不注射其他两个部位，可减少吞咽频率。内侧DVC预先注射SB334867可阻断第四脑室注射食欲素-A所引起的抑制反应。电损毁NTS的连合部，但不能消融AP，可取消第四脑室注射食欲素A对反射性吞咽的抑制作用。这些结果表明，食欲素-A通过位于NTS连合部和/或其附近的食欲素1受体抑制反射性吞咽。