Antidepressants recruit new neurons to improve stress response regulation.
Antidepressants recruit new neurons to improve stress response regulation.
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抗抑郁药募集新的神经元以改善压力反应调节。
DOI：
10.1038/mp.2011.48
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发表时间：
2011-12
影响因子：
11
通讯作者：
Belzung C
中科院分区：
文献类型：
--
作者：
Surget A;Tanti A;Leonardo ED;Laugeray A;Rainer Q;Touma C;Palme R;Griebel G;Ibarguen-Vargas Y;Hen R;Belzung C
最近的研究表明海马神经发生参与抗抑郁药的行为效应。然而，新生颗粒神经元可能影响抗抑郁反应的确切机制仍然难以捉摸。在这里，我们证明了不可预测的慢性轻度应激小鼠不仅减少海马神经发生，但也抑制海马和主要的应激激素系统，下丘脑-垂体-肾上腺（HPA）轴之间的关系。此外，这种关系通过抗抑郁药氟西汀治疗以神经发生依赖性方式恢复。具体而言，慢性应激严重损害HPA轴的活动，海马体的能力，以调节下游脑区参与应激反应，海马颗粒细胞网络的敏感性，新奇/糖皮质激素的影响和HPA轴的海马依赖性负反馈。值得注意的是，我们发现，虽然消融海马神经发生单独不损害HPA轴的活动，氟西汀恢复海马调节HPA轴在慢性应激条件下的能力，只发生在一个完整的神经原生态位的存在。这些发现为理解成人产生的新神经元如何影响抗抑郁药的反应提供了一个机制框架。我们认为，新产生的神经元可能有助于压力的整合，在慢性压力或抑郁症，增强神经发生使功能失调的海马恢复对压力反应系统的中央控制，然后允许恢复。
Recent research suggests an involvement of hippocampal neurogenesis in behavioral effects of antidepressants. However, the precise mechanisms through which newborn granule neurons might influence the antidepressant response remain elusive. Here, we demonstrate that unpredictable chronic mild stress in mice not only reduces hippocampal neurogenesis, but also dampens the relationship between hippocampus and the main stress hormone system, the hypothalamo-pituitary-adrenal (HPA) axis. Moreover, this relationship is restored by treatment with the antidepressant fluoxetine, in a neurogenesis-dependent manner. Specifically, chronic stress severely impairs HPA axis activity, the ability of hippocampus to modulate downstream brain areas involved in the stress response, the sensitivity of the hippocampal granule cell network to novelty/glucocorticoid effects and the hippocampus-dependent negative feedback of the HPA axis. Remarkably, we revealed that, although ablation of hippocampal neurogenesis alone does not impair HPA axis activity, the ability of fluoxetine to restore hippocampal regulation of the HPA axis under chronic stress conditions, occurs only in the presence of an intact neurogenic niche. These findings provide a mechanistic framework for understanding how adult-generated new neurons influence the response to antidepressants. We suggest that newly generated neurons may facilitate stress integration and that, during chronic stress or depression, enhancing neurogenesis enables a dysfunctional hippocampus to restore the central control on stress response systems, then allowing recovery.
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影响因子：
82.9
作者：
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