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

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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.