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Neuropsychopharmacology. 2015 Sep;40(10):2368-78. doi: 10.1038/npp.2015.85. Epub 2015 Apr 2.

Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.

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Department of Neuroscience, Columbia University, New York, NY, USA.
1] Center for Regenerative Medicine, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA [2] Harvard Stem Cell Institute, Boston, MA, USA [3] Harvard Medical School, Boston, MA, USA.
1] Department of Neuroscience, Columbia University, New York, NY, USA [2] Department of Psychiatry, Columbia University, New York, NY, USA [3] Department of Pharmacology, Columbia University, New York, NY, USA [4] Division of Integrative Neuroscience, The New York State Psychiatric Institute, New York, NY, USA.


Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects.

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