The first two authors contributed equally to this study.
Antidepressant drugs reverse the loss of adult neural stem cells following chronic stress
Version of Record online: 1 AUG 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 85, Issue 16, pages 3574–3585, December 2007
How to Cite
Hitoshi, S., Maruta, N., Higashi, M., Kumar, A., Kato, N. and Ikenaka, K. (2007), Antidepressant drugs reverse the loss of adult neural stem cells following chronic stress. J. Neurosci. Res., 85: 3574–3585. doi: 10.1002/jnr.21455
- Issue online: 20 NOV 2007
- Version of Record online: 1 AUG 2007
- Manuscript Accepted: 6 JUN 2007
- Manuscript Received: 22 MAR 2007
- Ministry of Education, Culture, Sports, Science and Technology of Japan. Grant Numbers: 16500251 (to S.H.), 17025041 (to S.H.)
- subventricular zone
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. © 2007 Wiley-Liss, Inc.