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Neural mechanisms and transmitters of the defense response against stress

应激防御反应的神经机制和递质

基本信息

批准号：
16590162
负责人：
KUWAKI Tomoyuki
金额：
$ 2.11万
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：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Stressor induces not only cognitive, emotional and behavioral changes but also autonomic changes. Although research on the neural circuits underlying such autonomic changes has implicated the hypothalamus in the defense response against stressors, neurotransmitters in this multifaceted and coordinated response have not been revealed. We have previously shown that some features of the defense response, such as increases in arterial blood pressure (AP), heart rate (HR), and ventilation were attenuated in prepro-orexin knockout mice (ORX-KO). Here we examined whether the same was true in orexin neuron-ablated mice (ORX/ATX-Tg). In addition, we examined the other features of the defense response ; skeletal muscular vasodilation and shift of baroreceptor reflex. Both in anesthetized and conscious conditions, basal AP in ORX/ATX-Tg was significantly lower by 〜20 mmHg than that in WT, as was the case in ORX-KO. The difference in AP was disappeared after treatment with an α-blacker but not with β-blocker, indicating lower sympathetic vasoconstrictor outflow. Stimulation of the perifomical area (PFA) in urethane-anesthetized ORX/ATX-Tg elicited smaller and shorter-lasting increases in AP, HR, and ventilation and skeletal muscle vasodilation than those in the wild-type controls (WT). In addition, air jet stress-induced elevations of AP and HR were attenuated in conscious ORX/ATX-Tg. After pretreatment with a β-blocker, atenolol, stimulation of PFA suppressed phenylephrine induced bradycardia in WT. This demonstrated the resetting of the baroreflex. In ORX/ATX-Tg, however, no significant suppression was observed. The present study provided further support for our hypothesis that orexin-containing neurons in PFA play a role as a master switch to activate multiple efferent pathways of the defense response and also operate as a regulator of basal AP.

应激不仅引起认知、情绪和行为的变化，而且引起自主神经的变化。尽管对这种自主神经变化背后的神经回路的研究表明，下丘脑参与了对压力源的防御反应，但这种多方面和协调反应中的神经递质尚未被揭示。我们先前已经表明，防御反应的一些特征，如动脉血压（AP），心率（HR）和通气量的增加在prepro-orexin敲除小鼠（ORX-KO）中减弱。在这里，我们研究了食欲素神经元消融小鼠（ORX/ATX-Tg）是否也是如此。此外，我们还研究了防御反应的其他特征：骨骼肌血管舒张和压力感受性反射的变化。在麻醉和清醒状态下，ORX/ATX-Tg中的基础AP比WT中的基础AP显著降低1020 mmHg，与ORX-KO中的情况相同。用α-blacker治疗后AP的差异消失，但用β-受体阻滞剂治疗后没有消失，表明交感血管收缩剂流出量较低。与野生型对照组（WT）相比，在麻醉的ORX/ATX-Tg中刺激骨周区（PFA）引起AP、HR、通气和骨骼肌血管舒张的增加更小且持续时间更短。此外，在清醒的ORX/ATX-Tg中，空气喷射应力诱导的AP和HR升高减弱。用β-受体阻滞剂阿替洛尔预处理后，刺激PFA可抑制苯肾上腺素诱发的WT心动过缓。这证明了压力反射的重置。然而，在ORX/ATX-Tg中，未观察到显著抑制。本研究为我们的假设提供了进一步的支持，即含食欲素的神经元在PFA中起着主开关的作用，激活防御反应的多个传出通路，也作为基础AP的调节器。