Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors
Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors
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DOI：
10.1038/npp.2015.85
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发表时间：
2015-09-01
影响因子：
7.6
通讯作者：
Hen, Rene
中科院分区：
文献类型：
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作者：
Hill, Alexis S.;Sahay, Amar;Hen, Rene
成人海马神经发生增加抗抑郁药，并需要他们的一些行为的影响。然而，目前尚不清楚扩大成年出生的神经元数量是否足以影响焦虑和抑郁相关的行为。在这里，我们使用一个诱导型转基因小鼠模型，其中促凋亡基因Bax被删除的神经干细胞和他们的后代在成年大脑，从而增加成年神经发生。我们发现对基线焦虑和抑郁相关行为没有影响;然而，我们发现增加成年神经发生足以减少长期用皮质酮（CORT）治疗的小鼠的焦虑和抑郁相关行为，这是一种小鼠应激模型。因此，在基线条件下和慢性应激模型中，神经发生对行为的影响不同。此外，我们发现，无论是在基线或慢性CORT给药后，成人海马神经发生增加对下丘脑-垂体-肾上腺（HPA）轴调节没有影响，这表明成人海马神经发生增加可以通过独立于HPA轴的机制影响焦虑和抑郁相关行为。使用未来的技术来特异性地抑制海马中的BAX可以用于增强成年神经发生，因此可能代表了一种促进抗抑郁样行为效应的新策略。
Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects.