Functional activation of CRH neurons and expression of the genes encoding CRH and its receptors in food-deprived lean (Fa/?) and obese (fa/fa) Zucker rats.
Functional activation of CRH neurons and expression of the genes encoding CRH and its receptors in food-deprived lean (Fa/?) and obese (fa/fa) Zucker rats.
复制标题
食物剥夺的瘦 (Fa/?) 和肥胖 (fa/fa) Zucker 大鼠中 CRH 神经元的功能激活以及编码 CRH 及其受体的基因的表达。
DOI：
10.1159/000127256
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发表时间：
1997
影响因子：
4.1
通讯作者：
D. Richard
中科院分区：
文献类型：
--
作者：
E. Timofeeva;D. Richard
研究了食物剥夺对瘦（Fa/?）和肥（Fa/ Fa） Zucker大鼠脑促肾上腺皮质激素释放激素（CRH）神经元功能激活和编码CRH及其受体1型（CRH1-R）和2 α (CRH2-R)基因表达的时间过程。Fa / ?将fa/fa大鼠分别给予0、3、6、12和24小时的食物剥夺期。在相同的脑切片上进行Fos免疫反应性和CRH mRNA的测量，以评估CRH神经元的激活状态。采用原位杂交组织化学方法检测编码CRH及其受体的mrna。在fa/fa大鼠中，食物剥夺诱导多个脑区CRH细胞快速表达Fos，包括室旁下丘脑核（PVN）、终纹床核（BNST）、前背视前核、内侧视前核、突起物质和巴林顿核。Fos免疫反应性和CRH mRNA的共定位在fa/fa大鼠的PVN中尤为明显，在禁食开始12小时后，细胞核旁细胞分裂的大多数CRH细胞显示Fos阳性细胞核。在肥胖大鼠中，食物剥夺还导致BNST中CRH mRNA水平升高，以及PVN和垂体前叶中CRH1-R的高表达和低表达。肥胖大鼠PVN中CRH1-R的表达发生在剥夺开始12 h后。在Fa / ?在大鼠中，食物剥夺没有引起CRH细胞的明显激活，BNST和杏仁核中央核CRH mRNA水平缓慢下降，下丘脑腹内侧核CRH2-R基因表达逐渐下降。这些结果表明，食物剥夺能够在肥胖的Zucker大鼠中产生一种类似压力的反应，这种反应转化为下丘脑-垂体-肾上腺轴的特别显著的激活。这种反应与Fa/？在大鼠中，食物剥夺对CRH系统的作用似乎与CRH在调节能量平衡方面的已知作用更相容。
The time course of the action of food deprivation on the functional activation of corticotropin-releasing hormone (CRH) neurons and on the expression of the genes encoding CRH and its receptors of type 1 (CRH1-R) and 2alpha (CRH2-R) in the brain were assessed in lean (Fa/?) and obese (fa/fa) Zucker rats. Fa/? and fa/fa rats were assigned to food deprivation periods of 0, 3, 6, 12, and 24 h. Measurements of Fos immunoreactivity and CRH mRNA were carried out on the same brain sections to assess the state of activation of CRH neurons. In situ hybridization histochemistry was employed to measure the mRNAs encoding CRH and its receptors. In fa/fa rats, food deprivation induced a rapid expression of Fos in CRH cells of several brain regions that include the paraventricular hypothalamic nucleus (PVN), the bed nucleus of the stria terminalis (BNST), the anterodorsal preoptic nucleus, the medial preoptic nucleus, the substantia innominata and Barrington's nucleus. The colocalization of Fos immunoreactivity and CRH mRNA was particularly noticeable in the PVN of fa/fa rats, where the majority of the CRH cells of the parvocellular division of the nucleus displayed Fos-positive nuclei, 12 h after the onset of fasting. In obese rats, food deprivation also produced an increase in the CRH mRNA levels in the BNST as well as high and low expressions of the CRH1-R in, respectively, the PVN and the anterior lobe of the pituitary. The expression of CRH1-R in the PVN of obese rats occurred 12 h after the onset of the deprivation. In Fa/? rats, food deprivation induced no marked activation of the CRH cells, a slow decrease in the CRH mRNA levels in the BNST and the central nucleus of the amygdala, and a gradual decrease in the expression of CRH2-R gene in the ventromedial hypothalamic nucleus. These results demonstrate that food deprivation is capable of generating in obese Zucker rats a stress-like response that translates into a particularly striking activation of the hypothalamic-pituitary-adrenal axis. This response contrasts with that observed in Fa/? rats, in which the action of food deprivation on the CRH system seems more compatible with the known effects of CRH in the regulation of energy balance.