Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling
Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling
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DOI：
10.1073/pnas.1003825107
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发表时间：
2010-07-20
影响因子：
11.1
通讯作者：
Baram, Tallie Z.
中科院分区：
文献类型：
--
作者：
Chen, Yuncai;Rex, Christopher S.;Baram, Tallie Z.
压力会影响海马体，这是大脑中对记忆至关重要的区域。在啮齿类动物中，急性应激可降低树突棘的密度、兴奋性突触的突触后元件的位置，并损害长时程增强和记忆。类固醇应激激素和神经递质与潜在机制有关，但促肾上腺皮质激素释放激素（CRH）的作用尚未阐明，CRH是一种下丘脑激素，在海马内应激时也会释放。此外，急性应激后脊柱丧失和记忆缺陷的因果关系尚不清楚。我们使用在海马神经元中表达YFP的转基因小鼠，发现5小时的应激导致学习和记忆的严重丧失。这种缺陷与海马CA 3区连合/联合通路中长时程增强和树突棘完整性的选择性破坏有关。个别小鼠的记忆缺陷程度与同一小鼠CA 3区顶端树突棘密度降低显著相关。此外，将CRH受体1型（CRFR 1）阻断剂NBI 30775直接注入大脑可预防应激诱导的脊柱丢失，并恢复应激受损的认知功能。我们的结论是，急性，长时间的压力损害学习和记忆的机制，破坏海马树突棘的完整性。此外，建立海马CRH-CRFR 1信号传导对这些过程的贡献突出了应激影响海马结构和功能的协调机制的复杂性。
Stress affects the hippocampus, a brain region crucial for memory. In rodents, acute stress may reduce density of dendritic spines, the location of postsynaptic elements of excitatory synapses, and impair long-term potentiation and memory. Steroid stress hormones and neurotransmitters have been implicated in the underlying mechanisms, but the role of corticotropin-releasing hormone (CRH), a hypothalamic hormone also released during stress within hippocampus, has not been elucidated. In addition, the causal relationship of spine loss and memory defects after acute stress is unclear. We used transgenic mice that expressed YFP in hippocampal neurons and found that a 5-h stress resulted in profound loss of learning and memory. This deficit was associated with selective disruption of long-term potentiation and of dendritic spine integrity in commissural/associational pathways of hippocampal area CA3. The degree of memory deficit in individual mice correlated significantly with the reduced density of area CA3 apical dendritic spines in the same mice. Moreover, administration of the CRH receptor type 1 (CRFR1) blocker NBI 30775 directly into the brain prevented the stress-induced spine loss and restored the stress-impaired cognitive functions. We conclude that acute, hours-long stress impairs learning and memory via mechanisms that disrupt the integrity of hippocampal dendritic spines. In addition, establishing the contribution of hippocampal CRH-CRFR1 signaling to these processes highlights the complexity of the orchestrated mechanisms by which stress impacts hippocampal structure and function.