Neonatal maternal separation in the rat impacts on the stress responsivity of central corticotropin-releasing factor receptors in adulthood
Neonatal maternal separation in the rat impacts on the stress responsivity of central corticotropin-releasing factor receptors in adulthood
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DOI：
10.1007/s00213-010-1885-9
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发表时间：
2011-03-01
影响因子：
3.4
通讯作者：
Cryan, John F.
中科院分区：
文献类型：
--
作者：
O'Malley, Dervla;Dinan, Timothy G.;Cryan, John F.
早期发育阶段的不良事件可诱导中枢应激回路的持续变化，导致成年后应激敏感性增加，这在母分离（MS）大鼠模型中很明显。人们普遍认为，应激肽促肾上腺皮质激素释放因子（CRF）通过结合CRF1和2受体（CRFR1和CRFR2）是这些表型变化的关键。这些研究旨在探讨母体分离对基础条件下和成年期急性心理应激源后CRFR1和CRFR2中枢表达的影响。采用Western blotting技术检测MS大鼠下丘脑、前额叶和额叶皮质、杏仁核和海马中受体表达与对照组相比的变化。此外，还评估了急性心理应激源（野外暴露）对这些变化的影响。在基础条件下，MS大鼠下丘脑中CRFR1水平升高。暴露于急性应激对未分离动物的影响有限，但会引起MS大鼠下丘脑、前额叶皮层和海马中CRFR1的显著变化。此外，在MS大鼠的杏仁核中观察到应激诱导的CRFR2升高。这些数据表明，在母亲分离后，大脑CRF系统对急性应激的反应发生了离散而显著的变化。这些研究表明，早期生活扰动诱导中枢CRF受体表达的持续变化和对压力的敏感性增加，这可能有助于在这些动物中观察到的与压力相关的行为变化。
Adverse events during early developmental stages can induce persistent changes in central stress circuits, leading to increased stress sensitivity in adulthood, as is apparent in the maternally separated (MS) rat model. It is widely accepted that the stress peptide corticotropin-releasing factor (CRF) by binding to CRF1 and 2 receptors (CRFR1 and CRFR2) is key to these phenotypic changes.These studies aim to investigate the effects of maternal separation on central expression of CRFR1 and CRFR2 under basal conditions and following an acute psychological stressor in adulthood.Western blotting techniques were employed to examine changes in receptor expression in the hypothalamus, pre-frontal and frontal cortices, amygdala and hippocampus of MS rats as compared to controls. Additionally, the effects of an acute psychological stressor (open field exposure) on these changes were assessed.Under basal conditions, CRFR1 was elevated in the hypothalamus of MS rats. Exposure to an acute stress had limited effects in non-separated animals but induced significant changes in CRFR1 in the hypothalamus, pre-frontal cortex and hippocampus of MS rats. Additionally, stress-induced increases in CRFR2 were observed in the amygdala of MS rats.These data demonstrate the discrete and significant alterations in how the brain CRF system responds to acute stress following maternal separation. These studies illustrate that early life perturbations induce persistent changes in central CRF receptor expression and increased sensitivity to stress, which may contribute to the stress-related behavioural changes observed in these animals.