5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response.
5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response.
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DOI：
10.1038/nn.4116
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发表时间：
2015-11
影响因子：
25
通讯作者：
Hen R
中科院分区：
文献类型：
--
作者：
Samuels BA;Anacker C;Hu A;Levinstein MR;Pickenhagen A;Tsetsenis T;Madroñal N;Donaldson ZR;Drew LJ;Dranovsky A;Gross CT;Tanaka KF;Hen R
选择性5-羟色胺再摄取抑制剂(SSRI)是广泛使用的抗抑郁药，但它们影响行为的机制只有部分得到解决。成年海马神经发生对于SSRIs的某些反应是必需的，但尚不清楚成熟的齿状回颗粒细胞(成熟的DG GC)是否也起作用。我们从DG GC中特异性地删除了5-羟色胺1A受体(5HT1AR；一种SSRI反应所需的受体)，发现SSRI氟西汀对行为和下丘脑-垂体-肾上腺轴(HPA)的影响被取消。相比之下，只在幼年出生颗粒细胞(AbGC)中缺乏5HT1ARs的小鼠表现出正常的氟西汀反应。重要的是，被设计为仅在DG GC中表达功能性5HT1AR的5HT1AR缺陷小鼠对氟西汀有反应，表明DG GC中的5HT1AR足以介导抗抑郁反应。综上所述，这些数据表明，成熟的DG GC和年轻的abGC都必须参与抗抑郁反应。
Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants, but the mechanisms by which they influence behavior are only partially resolved. Adult hippocampal neurogenesis is necessary for some of the responses to SSRIs, but it is unknown whether the mature dentate gyrus granule cells (mature DG GCs) also contribute. We deleted Serotonin 1A receptor (5HT1AR; a receptor required for the SSRI response) specifically from DG GCs and found that the effects of the SSRI fluoxetine on behavior and the Hypothalamic-Pituitary-Adrenal (HPA) axis were abolished. By contrast, mice lacking 5HT1ARs only in young adult born granule cells (abGCs) showed normal fluoxetine responses. Importantly, 5HT1AR deficient mice engineered to express functional 5HT1ARs only in DG GCs responded to fluoxetine, indicating that 5HT1ARs in DG GCs are sufficient to mediate an antidepressant response. Taken together, these data indicate that both mature DG GCs and young abGCs must be engaged for an antidepressant response.