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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / drug therapy
  • Anxiety / pathology*
  • Bromodeoxyuridine / metabolism
  • Corticosterone / blood
  • Corticosterone / pharmacology
  • Corticosterone / therapeutic use
  • Depression / pathology*
  • Disease Models, Animal
  • Doublecortin Domain Proteins
  • Exploratory Behavior / drug effects
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hypothalamo-Hypophyseal System / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis / drug effects
  • Neurogenesis / genetics
  • Neurogenesis / physiology*
  • Neuropeptides / metabolism
  • Pituitary-Adrenal System / drug effects
  • Tamoxifen / pharmacology
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Doublecortin Domain Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides
  • bcl-2-Associated X Protein
  • Tamoxifen
  • Bromodeoxyuridine
  • Corticosterone