Inhibitory Function of the Dorsomedial Hypothalamic Nucleus on the Hypothalamic-Pituitary-Adrenal Axis Response to an Emotional Stressor but not Immune Challenge
Inhibitory Function of the Dorsomedial Hypothalamic Nucleus on the Hypothalamic-Pituitary-Adrenal Axis Response to an Emotional Stressor but not Immune Challenge
复制标题
DOI：
10.1111/j.1365-2826.2012.02369.x
复制
发表时间：
2013-01-01
影响因子：
3.2
通讯作者：
Singewald, N.
中科院分区：
文献类型：
--
作者：
Ebner, K.;Muigg, P.;Singewald, N.
越来越多的证据表明下丘脑背内侧核（DMH）参与自主神经和神经内分泌应激反应的调节。然而，尽管已经描述了从 DMH 到室旁下丘脑核 (PVN)（神经内分泌应激轴的关键部位）的投射，但 DMH 神经元在应激期间调节下丘脑-垂体-肾上腺 (HPA) 轴激活的影响尚不完全清楚。本研究旨在探讨 DMH 在 HPA 轴对不同类型刺激的反应中的作用。装有慢性颈静脉导管的雄性 Sprague-Dawley 大鼠暴露于情绪应激源（升高的平台暴露）或免疫挑战（全身白细胞介素 1 β 给药）。 DMH 的双侧电解损伤抑制了 HPA 轴对情绪应激源的反应，与假损伤对照相比，损伤动物在升高的平台暴露期间和之后血浆促肾上腺皮质激素水平较高，表明这一点。此外，DMH 损伤的动物在 PVN 中表现出神经元激活增加，与对照组相比，在升高的平台暴露后 c-Fos 表达更高。相比之下，DMH 损伤对 HPA 轴对免疫攻击的反应没有影响。总而言之，我们的数据表明 DMH 神经元对压力诱导的 HPA 轴激活的抑制作用取决于刺激的性质，该刺激对于情绪压力源的反应很重要，但对于免疫挑战则不重要。
Accumulating evidence implicates the dorsomedial hypothalamic nucleus (DMH) in the regulation of autonomic and neuroendocrine stress responses. However, although projections from the DMH to the paraventricular hypothalamic nucleus (PVN), which is the critical site of the neuroendocrine stress axis, have been described, the impact of DMH neurones in the modulation of hypothalamic-pituitary-adrenal (HPA) axis activation during stress is not fully understood. The present study aimed to investigate the role of the DMH in HPA axis responses to different types of stimuli. Male Sprague-Dawley rats fitted with a chronic jugular venous catheter were exposed to either an emotional stressor (elevated platform-exposure) or immune challenge (systemic interleukin-1 beta administration). Bilateral electrolytic lesions of the DMH disinhibited HPA axis responses to the emotional stressor, as indicated by higher plasma adrenocorticotrophic hormone levels during and after elevated platform exposure in lesioned animals compared to sham-lesioned controls. Moreover, DMH-lesioned animals showed increased neuronal activation in the PVN, as indicated by a higher c-Fos expression after elevated-platform exposure compared to controls. By contrast, DMH-lesions had no effects on HPA axis responses to immune challenge. Taken together, our data suggest an inhibitory role of DMH neurones on stress-induced HPA axis activation that is dependent upon the nature of the stimulus being important in response to an emotional stressor but not to immune challenge.