权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

EFFERENT MECHANISMS OF DEFENSE RESPONSE FROM THE HYPOTHALAMUS

下丘脑防御反应的传出机制

基本信息

批准号：
14570037
负责人：
KUWAKI Tomoyuki
金额：
$ 1.73万
依托单位：
CHIBA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570037/
关键词：
HYPOTHALAMUS DEFENSE RESPONSE OREXIN STRESS KNOCKOUT MICE SYMPATHETIC NERVOUS SYSTEM USA INTERNATIONAL INFORMATION EXCHANGE 防衛反射

项目摘要

The perifornical area of the hypothalamus has been known as the center for defense response, or "fight or flight" response, which is characterized by concomitant rise in arterial blood pressure (AP), heart rate (HR), and respiratory frequency (Rf). We examined whether orexin, a recently identified hypothalamic neuropeptide, contributes to the defense response and basal cardiovascular regulation using orexin knockout mice. Microinjection of a GABA-A receptor antagonist, bicuculline methiodide, to the perifornical area in urethane-anesthetized wild-type mice elicited dose-dependent increases in AP, HR, and Rf. Although similar changes were observed in orexin knockout mice, intensities were smaller and duration was shorter than those in wild-type mice.Moreover, in an awake and freely moving condition, telemeter-indwelling orexin knockout mice showed diminished cardiovascular and behavioral responses to emotional stress in the resident-intruder test. We also found that basal AP in orexin knockout mice was significantly lower by 〜20 mmHg in both anesthetized and awake conditions. Alpha-adrenergic blockade with prazosin or ganglion blockade with hexamethonium cancelled the difference in basal AP. HR and cardiac contractile parameters by echocardiography did not differ between the two strains of mice. These results indicate lower sympathetic vasoconstrictor tone in knockout mice. The present study suggests that orexin-containing neurons in the perifornical area play a crucial role as one of the efferent pathways of defense response and also operate as a regulator of AP at basal condition by activating sympathetic outflow.

下丘脑的穹窿周围区域被称为防御反应中心，或“战斗或逃跑”反应，其特征在于伴随动脉血压（AP），心率（HR）和呼吸频率（Rf）的升高。我们研究食欲素，最近发现的下丘脑神经肽，是否有助于防御反应和基础心血管调节使用食欲素基因敲除小鼠。将GABA-A受体拮抗剂甲碘荷包牡丹碱（bicuculline methiodide）微量注射到麻醉的野生型小鼠穹窿周围区，引起AP、HR和Rf的剂量依赖性增加。尽管在食欲素基因敲除小鼠中观察到类似的变化，但强度较小，持续时间较短，而且，在清醒和自由活动的条件下，遥测仪留置食欲素基因敲除小鼠在居民入侵者测试中显示出对情绪应激的心血管和行为反应减少。我们还发现，在麻醉和清醒条件下，食欲素敲除小鼠的基础AP显著降低了1020 mmHg。α-肾上腺素能阻滞与哌唑嗪或神经节阻滞与六甲双铵取消了基础AP的差异。通过超声心动图测量的心率和心脏收缩参数在两种小鼠之间没有差异。这些结果表明基因敲除小鼠的交感血管收缩张力较低。目前的研究表明，含食欲素的神经元在穹窿周围区起着至关重要的作用，作为防御反应的传出通路之一，也作为AP的调节器在基础条件下通过激活交感神经流出。