Stress-induced cardiac stimulation and fever: Common hypothalamic origins and brainstem mechanisms
Stress-induced cardiac stimulation and fever: Common hypothalamic origins and brainstem mechanisms
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DOI：
10.1016/j.autneu.2006.02.010
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发表时间：
2006-06-30
影响因子：
2.7
通讯作者：
Zaretsky, Dmitry V.
中科院分区：
文献类型：
--
作者：
DiMicco, Joseph A.;Sarkar, Sumit;Zaretsky, Dmitry V.
我们过去的结果提供了相当多的证据表明，下丘脑背内侧(DMH)区域神经元的激活在大鼠“情绪”应激的许多典型效应的产生中起关键作用，包括激活下丘脑-垂体-肾上腺(HPA)轴，这是应激反应的神经内分泌标志，以及交感介导的心动过速。最近，我们证明：(1)向延髓中缝大核(RP)微量注射GABA(A)受体激动剂Muscimol，显著减弱由DMH化学刺激或实验性应激引起的心动过速；DMH介导刺激性心动过速的特定亚区对应于投射到RP的神经元密集集中的下丘脑背侧区(DHA)。因此，从DHA中的神经元到RP中的交感运动前神经元的通路可能构成了调节情绪应激中的心率增加的关键继电器--这一作用以前从未被提出过。相反，已知交感前运动神经元存在于RP中，但与交感温度调节机制关系最密切，包括激活棕色脂肪，这是大鼠非颤抖发热的主要手段，以及尾部皮肤血管收缩，这是该物种保存体温的重要方法。这些交感神经效应有助于在寒冷的环境中保持体温，或者在发烧时增加体温--通常伴随着心动过速。有趣的是，我们和其他人现在已经证明：(1)DMH中神经元的解除抑制也会增加体温，至少部分是通过激活棕色脂肪，(2)向DMH中微量注射神经元抑制剂蝇草酚可以减少实验性发热和相关的大鼠心动过速。我们假设，DMH中神经元的激活既介导了实验性“情绪”应激和发热所产生的体温升高和心脏刺激，而且这些影响在很大程度上是通过直接投射到RR的交感运动前神经元来介导的，因此，这一途径可能构成了一个共同的效应电路，各种前脑输入在该回路上汇聚，以响应不同的环境挑战。(C)2006爱思唯尔B.V.保留所有权利。
Our past results provide considerable evidence that activation of neurons somewhere in the region of the dorsomedial hypothalamus (DMH) plays a key role in the generation of many of the effects typically seen in "emotional" stress in rats, including activation of the hypothalamic-pituitary-adrenal (HPA) axis, the neuroendocrine hallmark of the generalized response to stress, and sympathetically mediated tachycardia, More recently, we demonstrated that (1) the tachycardia resulting either from chemical stimulation of the DMH or from experimental stress is markedly attenuated by microinjection of the GABA(A) receptor agonist muscimol, a neuronal inhibitor, into the medullary raphe pallidus (RP); and (2) the specific subregion of the DMH mediating stimulation-induced tachycardia corresponds to the dorsal hypothalamic area (DHA), a site where neurons projecting to the RP are densely concentrated. Thus, the pathway from neurons in the DHA to sympathetic premotor neurons in the RP may constitute a key relay mediating the increases in heart rate seen in emotional stress - a role that had never been proposed previously for either of these regions. Instead, sympathetic premotor neurons were known to exist in the RP but had been most closely associated with sympathetic thermoregulatory mechanisms, including activation of brown fat, the principal means for nonshivering thermogenesis in rats, and cutaneous vasioconstriction in the tail, an important method of conserving body heat in this species. These sympathetic effects serve to maintain body temperature in a cold environment or to increase it in fever - and are typically accompanied by tachycardia. Interestingly, we and others have now shown that (1) disinhibition of neurons in the DMH also increases body temperature, at least in part through activation of brown fat, (2) microinjection of the neuronal inhibitor muscimol into the DMH reduces experimental fever and the associated tachycardia in rats. We hypothesize that activation of neurons in the DMH mediates both the increased body temperature and cardiac stimulation produced in rats by experimental "emotional" stress and fever, and that these effects are mediated in large part through direct projections to sympathetic premotor neurons in the RR Thus, this pathway may constitute a common effector circuit upon which a variety of forebrain inputs converge in response to diverse environmental challenges. (c) 2006 Elsevier B.V. All rights reserved.