Orexins/Hypocretins Act in the Posterior Paraventricular Thalamic Nucleus During Repeated Stress to Regulate Facilitation to Novel Stress
Orexins/Hypocretins Act in the Posterior Paraventricular Thalamic Nucleus During Repeated Stress to Regulate Facilitation to Novel Stress
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DOI：
10.1210/en.2011-1652
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发表时间：
2011-12-01
期刊：
影响因子：
4.8
通讯作者：
Bhatnagar, Seema
中科院分区：
文献类型：
--
作者：
Heydendael, Willem;Sharma, Kanika;Bhatnagar, Seema
食欲素/下丘脑分泌素大量支配丘脑室旁核 (pPVT) 的后部，表达两种食欲素受体类型。 pPVT 对于适应重复压力很重要，特别是在重复压力暴露后促进新压力的能力。在这里，我们研究了 pPVT 中的食欲素如何调节 4 天重复游泳应激后下丘脑 - 垂体 - 肾上腺 (HPA) 对新约束的反应。在新的抑制之前用 SB334867 阻断 pPVT 中的食欲素受体不会改变促进的 HPA 反应。然而，每天四次游泳之前阻断食欲素受体可以阻止促进的ACTH并促进下丘脑c-Fos对约束的反应以及反复游泳应激引起的室旁下丘脑中CRH mRNA的增加。这些结果表明，在游泳的 4 d 期间，pPVT 中的食欲素作用对于促进 HPA 对异型约束的反应是必要的，但在约束期间则不然。第四次游泳导致食欲素1受体从膜部分转移到胞质部分。 OrexinA 还改变了 pPVT 细胞的放电模式，使反复游泳应激的大鼠比未应激的大鼠反应更灵敏。总之，结果表明 pPVT 中由 orexin1 受体介导的 orexin 作用对于适应重复应激的能力非常重要。 （内分泌学152：4738-4752，2011）
Orexins/hypocretins heavily innervate the posterior division of the paraventricular nucleus of the thalamus (pPVT), which expresses both orexin receptor types. The pPVT is important for adaptations to repeated stress, particularly the ability to facilitate to novel stress after repeated stress exposure. Here, we examined how orexins acting in the pPVT regulate facilitation of hypothalamic-pituitary-adrenal (HPA) responses to novel restraint after 4 d of repeated swim stress. Blockade of orexin receptors in the pPVT with SB334867 before novel restraint did not change the facilitated HPA response. However, blockade of orexin receptors before each of four daily swim exposures prevented the facilitated ACTH and facilitated hypothalamic c-Fos response to restraint as well as the repeated swim stress-induced increase in CRH mRNA in the paraventricular hypothalamus. These results suggest that orexin actions in the pPVT during the 4 d of swim, but not during restraint, are necessary for the facilitated HPA response to heterotypic restraint. Exposure to the fourth swim produced a shift in orexin1 receptors from membrane to cytosolic fractions. OrexinA also changed the firing patterns of pPVT cells to be more responsive in repeatedly swim stressed rats compared with nonstressed rats. Together, the results suggest that orexin actions in the pPVT, mediated by orexin1 receptors, are important for the ability to adapt to repeated stress. (Endocrinology 152: 4738-4752, 2011)