Expression of hypothalamic neuropeptides and the desensitization of pituitary-adrenal axis and hypophagia in the endotoxin tolerance
Expression of hypothalamic neuropeptides and the desensitization of pituitary-adrenal axis and hypophagia in the endotoxin tolerance
复制标题
DOI：
10.1016/j.yhbeh.2007.07.006
复制
发表时间：
2007-11-01
影响因子：
3.5
通讯作者：
Elias, L. L. K.
中科院分区：
文献类型：
--
作者：
Borges, B. C.;Antunes-Rodrigues, J.;Elias, L. L. K.
反复暴露于脂多糖（LPS）可诱导下丘脑-垂体-肾上腺轴（HPA）反应脱敏和食欲减退。我们研究了单次或多次注射LPS后，参与控制食物摄入和HPA轴活动的神经回路之间的相互作用。雄性Wistar大鼠接受单次或重复腹膜内注射LPS（100 μ g/kg）6天，并分成4组：6个盐水组、5个盐水+ 1个LPS组、5个LPS + 1个盐水组和6个LPS组。单次暴露于LPS的动物显示ACTH、CORT、PRL、TNF-α的血浆水平增加，并且下丘脑室旁核中的CRF mRNA也增加。这些动物表现出与弓状核（ARC）中CART表达增加相关的摄食量和体重减少。血浆瘦素水平没有改变。另一方面，与单次LPS或生理盐水处理相比，重复LPS给药不改变ACTH、CORT、PRL和TNF-α，但降低了瘦素水平。此外，重复LPS给药并不增加CRF或CART mRNA表达。重复注射LPS后的食物摄入量和体重增加与盐水处理的动物没有差异。单次或多次注射LPS后，ARC中NPY和POMC mRNA的表达无变化。总之，通过反复暴露于LPS诱导的脱敏涉及HPA轴激活和促凋亡反应的阻断，这两者都与下丘脑中TNF-α产生和CRF和CART表达的无反应性相关。(C)2007年爱思唯尔公司All rights reserved.
Repeated exposure to lipopolysaccharide (LPS) induces desensitization of hypothalamus-pituitary-adrenal axis (HPA) responses and hypophagia. We investigated the interplay between the neural circuitries involved in the control of food intake and HPA axis activity following single or repeated LPS injections. Male Wistar rats received a single or repeated i.p. injection of LPS (100 mu g/kg) for 6 days and were subdivided into four groups: 6 saline, 5 saline+ 1 LPS, 5 LPS + 1 saline and 6 LPS. Animals with a single exposure to LPS showed increased plasma levels of ACTH, CORT, PRL, TNF-alpha and also CRF mRNA in the paraventricular nucleus of the hypothalamus. These animals exhibited a reduced food intake and body weight associated with an increase of CART expression in the arcuate nucleus (ARC). Leptin plasma levels were not altered. On the other hand, repeated LPS administration did not alter ACTH, CORT, PRL and TNF-alpha, but it reduced leptin level, compared to single LPS or saline treatment. Furthermore, repeated LPS administration did not increase CRF or CART mRNA expression. Food intake and weight gain after repeated LPS injections were not different from saline-treated animals. There was no change in NPY and POMC mRNA expression in the ARC after single or repeated injections of LPS. In conclusion, desensitization induced by repeated exposure to LPS involves the blockade of HPA axis activation and anorexigenic response, which are both associated with an unresponsiveness of TNF-alpha production and CRF and CART expression in the hypothalamus. (C) 2007 Elsevier Inc. All rights reserved.