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The Journal of Neuroscience, March 14, 2007, 27(11):2734-2743; doi:10.1523/JNEUROSCI.3849-06.2007

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Development/Plasticity/Repair
Acute Psychosocial Stress Reduces Cell Survival in Adult Hippocampal Neurogenesis without Altering Proliferation

Rosanne M. Thomas, Gregory Hotsenpiller, and Daniel A. Peterson

Neural Repair and Neurogenesis Laboratory, Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064

Correspondence should be addressed to Daniel A. Peterson, Neural Repair and Neurogenesis Laboratory, Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064. Email: daniel.peterson{at}rosalindfranklin.edu

Factors modulating neurogenesis may contribute to the pathophysiology of affective disorders such as major depression. Environmental stressors in animal models have been proposed to alter neurogenesis, suggesting a mechanism for this contribution. The effect of an acute psychosocial stressor on either proliferation or survival (immediate, short term, and long term) was examined along with subsequent neuronal differentiation in the hippocampus of adult male Sprague Dawley rats. Subjects were exposed to a widely used social dominance paradigm that elicits behavioral and physiological responses to an acute psychosocial stressor. This social dominance paradigm may mimic human relational stress more realistically than laboratory stressors and provides a socially relevant model. We found that exposure to an acute psychosocial stressor at the time of cell generation resulted in a decreased number of newly generated cells in the hippocampus. By using sequential thymidine analog administration to provide temporal discrimination of DNA replication, we showed that short-term survival but not initial proliferation or immediate survival was altered in response to stress. Furthermore, we determined that stress experienced subsequent to proliferation also diminished long-term survival of cells. Thus, an acute episode of a social stress produces long-lasting effects on the incorporation of new hippocampal neurons by reducing their survival.

Key words: depression; dentate gyrus; cell cycle; confocal stereology; IdU; CldU


Received Sept. 5, 2006; revised Jan. 10, 2007; accepted Jan. 29, 2007.

Correspondence should be addressed to Daniel A. Peterson, Neural Repair and Neurogenesis Laboratory, Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064. Email: daniel.peterson{at}rosalindfranklin.edu


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