Differential Effect of Prenatal Stress on the Expression of Cortiocotrophin-Releasing Hormone and its Receptors in the Hypothalamus and Amygdala in Male and Female Rats
Differential Effect of Prenatal Stress on the Expression of Cortiocotrophin-Releasing Hormone and its Receptors in the Hypothalamus and Amygdala in Male and Female Rats
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DOI：
10.1111/j.1365-2826.2011.02117.x
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发表时间：
2011-04-01
影响因子：
3.2
通讯作者：
Weinstock, M.
中科院分区：
文献类型：
--
作者：
Zohar, I.;Weinstock, M.
本研究检测了妊娠第 13-20 天的大鼠产前应激对高架十字迷宫 (EPM) 中焦虑行为的影响，以及雄性和雌性后代的促肾上腺皮质激素释放激素 (CRH)、其受体 CRHR1 和 CRHR2，以及室旁核 (PVN) 和杏仁核中 CRH 结合蛋白 (CRH-BP) 的基因表达变化。产前应激 (PS) 的男性和女性在 EPM 中都表现出高度的焦虑。产前应激不会改变雄性 PVN 中 CRH 或其受体的基因表达，尽管它会降低 CRH-BP mRNA，从而增强游离 CRH 的活性。在PS雌性的PVN中，CRH的表达增加，同时CRHR2和CRH-BP的表达减少。这些变化与女性下丘脑垂体肾上腺轴对压力的更大激活相一致。 PS大鼠的焦虑行为与雄性杏仁核中CRHR2 mRNA和CRH-BP mRNA的减少以及雌性CRH mRNA的增加和CRHR2 mRNA的减少有关。在暴露于高架十字迷宫的急性应激后两小时，其中表现出高度的焦虑，仅在女性杏仁核中观察到 CRH 和 CRHR1 信号传导增加，而 CRHR2 mRNA 在两性中均减少。数据显示，产前应激和成年期急性应激对大鼠PVN和杏仁核中CRH及其受体和结合蛋白的表达具有不同的性别依赖性影响。
The present study examined the effect of prenatal stress in rats from days 13-20 of gestation on anxiogenic behaviour in the elevated plus maze (EPM) together with changes in the gene expression of corticotrophin-releasing hormone (CRH), its receptors, CRHR1 and CRHR2, as well as CRH binding protein (CRH-BP) in the paraventricular nucleus (PVN) and amygdala of their male and female offspring. Both prenatally-stressed (PS) males and females showed heightened anxiety in the EPM. Prenatal stress did not alter the gene expression of CRH or its receptors in the male PVN, although it decreased CRH-BP mRNA, which could augment the activity of free CRH. In the PVN of PS females, there was an increase in the expression of CRH, coupled with a decrease in that of CRHR2 and CRH-BP. These changes are compatible with the greater activation of the hypothalamic pituitary adrenal axis to stress in females. Anxiogenic behaviour of PS rats was associated with a reduction of CRHR2 mRNA and of CRH-BP mRNA in the amygdala of males and an increase in CRH mRNA and decrease in CRHR2 mRNA in females. Two hours after acute stress of exposure to the elevated plus maze in which heightened anxiety was manifested, increases were seen only in the amygdala of females in CRH and CRHR1 signalling, whereas CRHR2 mRNA was reduced in both sexes. The data show that both prenatal stress and acute stress in adulthood have a differential sex-dependent effect on the expression of CRH its receptors and binding protein in the PVN and amygdala of rats.