Antidepressant drugs reverse the loss of adult neural stem cells following chronic stress
Antidepressant drugs reverse the loss of adult neural stem cells following chronic stress
复制标题
DOI：
10.1002/jnr.21455
复制
发表时间：
2007-12-01
影响因子：
4.2
通讯作者：
Ikenaka, Kazuhiro
中科院分区：
文献类型：
--
作者：
Hitoshi, Seiji;Maruta, Noriko;Ikenaka, Kazuhiro
在啮齿类动物中，成年神经发生发生在嗅球和海马齿状回。已经表明，暴露于心理社会压力会减少齿状回中的细胞增殖。然而，很少有人知道压力如何影响神经干细胞（NSCs）在脑室下区（SVZ），提供新的神经元的嗅球的增殖动力学。我们利用小鼠强迫游泳应激模型，发现慢性应激减少了SVZ中的神经干细胞数量。神经干细胞数量的减少在压力停止后持续了数周，但通过抗抑郁药物氟西汀和丙咪嗪的治疗得以逆转。我们通过体外集落形成神经球实验证明，皮质酮减弱了成体神经干细胞的神经球形成，相反，5-羟色胺增加了神经干细胞的存活。此外，当5-羟色胺被注入侧脑室时，它在体内扩大了SVZ中的NSC池的大小。这些结果表明，在慢性应激条件下，神经干细胞的数量是由糖皮质激素和5-羟色胺的作用。这些数据提供了深入了解抗抑郁药物药理作用的分子机制。(C)2007 Wiley-Liss，Inc.
In rodents, adult neurogenesis occurs in the olfactory bulb and the dentate gyrus of the hippocampus. It has been shown that exposure to psychosocial stress reduces cell proliferation in the dentate gyrus. However, little is known about how stress affects the proliferation kinetics of neural stem cells (NSCs) in the subventricular zone (SVZ), which provide new neurons to the olfactory bulb. We utilized a forced-swim model of stress in the mouse and found that chronic stress decreased the number of NSCs in the SVZ. The reduction of NSC number persisted for weeks after the cessation of stress but was reversed by treatment with the antidepressant drugs fluoxetine and imipramine. We demonstrated by in vitro colony-forming neurosphere assay that corticosterone attenuated neurosphere formation by adult NSCs and, in contrast, that serotonin increased the survival of NSCs. In addition, serotonin expanded the size of the NSC pool in the SVZ when it was infused into the lateral ventricle in vivo. These results suggest that, under chronic stress conditions, the number of NSCs is regulated by the actions of glucocorticoids and serotonin. These data provide insights into the molecular mechanisms underlying the pharmacological actions of antidepressant drugs. (C) 2007 Wiley-Liss, Inc.