Early maternal separation followed by later stressors leads to dysregulation of the HPA-axis and increases in hippocampal NGF and NT-3 levels in a rat model
Early maternal separation followed by later stressors leads to dysregulation of the HPA-axis and increases in hippocampal NGF and NT-3 levels in a rat model
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DOI：
10.1007/s11011-006-9013-6
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发表时间：
2006-09-01
影响因子：
3.6
通讯作者：
Daniels, Willie M. U.
中科院分区：
文献类型：
--
作者：
Faure, Jacqueline;Uys, Joachim D. K.;Daniels, Willie M. U.
早期不良生活事件，随后的压力源，似乎增加了人类随后发病的精神疾病的易感性。这种现象背后的分子机制尚不清楚，但HPA轴的失调和神经营养因子的改变已被牵连。本研究研究了啮齿动物早期母亲分离，随后在青春期和成年期的压力对后期hpa轴活性和海马神经营养因子（脑源性神经营养因子、神经生长因子和神经营养因子-3）水平的影响。与对照组相比，反复应激大鼠基底ACTH （p < 0.05）和CORT （p < 0.05）水平显著降低，海马背侧和腹侧NGF （p < 0.001）和海马背侧NT-3水平显著升高（p < 0.01）。多重应激后下丘脑轴的失调与以往的临床前和临床研究一致。鉴于神经营养因子在神经元存活和可塑性中起重要作用，有可能推测它们的升高反映了一种代偿机制。
Early adverse life events, followed by subsequent stressors, appear to increase susceptibility for subsequent onset of psychiatric disorders in humans. The molecular mechanisms that underlie this phenomenon remain unclear, but dysregulation of the HPA axis and alterations in neurotrophic factors have been implicated. The present study investigated the effects in rodents of early maternal separation, followed by stress in adolescence and adulthood on later HPA-axis activity and hippocampal neurotrophin levels (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3). Animals subjected to repeated stressors showed a significant decrease in basal ACTH (p < 0.05) and CORT (p < 0.05) levels when compared to controls, as well as significantly increased levels of NGF in the dorsal (p < 0.001) and ventral hippocampus (p < 0.01), and of NT-3 in the dorsal hippocampus (p < 0.01). Dysregulation of the HPA axis after multiple stressors is consistent with previous preclinical and clinical work. Given that neurotrophins are important in neuronal survival and plasticity, it is possible to speculate that their elevation reflects a compensatory mechanism.