Dynamics of neural stem cells in the adult mammalian brain under stress conditions.

成年神经发生发生在啮齿动物的嗅球和海马齿状回（DG），可能在脑功能中起重要作用。暴露于社会心理压力后，DG中的细胞增殖减少，但这种减少的分子和细胞机制仍有待阐明。在本研究中，我们利用小鼠应激的强迫游泳模型来确定慢性应激对脑室下区（SVZ）神经干细胞（NSCs）的影响。慢性应激降低了SVZ中NSCs的数量，这种减少在应激停止后持续数周，但通过抗抑郁药物治疗被逆转。体内双侧肾上腺切除术可阻断慢性应激对NSCs的影响，体外实验中皮质酮可减弱成人NSCs形成的神经球。相比之下，血清素在体外暴露时增加了NSCs的存活率，在体内侧脑室注入血清素时扩大了SVZ中NSC池的大小。这些结果表明，慢性应激条件下NSCs的数量受糖皮质激素和血清素作用之间的平衡调节，并为抗抑郁药物药理作用的分子机制提供了新的见解。

Adult neurogenesis, which occurs in the olfactory bulb and dentate gyrus (DG) of the hippocampus in rodents, may play significant roles in brain function. Cell proliferation in the DG is reduced after exposure to psychosocial stress, yet the molecular and cellular mechanisms underlying this reduction remain to be elucidated. In the present study, we utilize the forced swim model of stress in the mouse to determine the effects of chronic stress on neural stem cells (NSCs) in the subventricular zone (SVZ). Chronic stress decreased the number of NSCs in the SVZ, the decrease persisted for weeks after the cessation of stress, but was reversed by treatment with antidepressant drugs. The effects of chronic stress on NSCs are blocked by bilateral adrenalectomy in vivo, and corticosterone attenuates neurosphere formation by adult NSCs in vitro. In contrast, serotonin increased survival of the NSCs when exposure was in vitro and expanded the size of NSC pool in the SVZ when serotonin was infused to the lateral ventricle in vivo. These results suggest that the number of NSCs under chronic stress conditions are regulated by the balance between the action of glucocorticoids and serotonin and provide an insight to the molecular mechanisms underlying pharmacological action of antidepressant drugs.