Neurofibromin modulates adult hippocampal neurogenesis and behavioral effects of antidepressants
Li, Yun, Li, Yanjiao, McKay, Renée M., Riethmacher, Dieter and Parada, Luis F. (2012) Neurofibromin modulates adult hippocampal neurogenesis and behavioral effects of antidepressants. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 32, (10), 3529-3539. (doi:10.1523/JNEUROSCI.3469-11.2012). (PMID:22399775).
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Neurogenesis persists in the rodent dentate gyrus (DG) throughout adulthood but declines with age and stress. Neural progenitor cells (NPCs) residing in the subgranular zone of the DG are regulated by an array of growth factors and respond to the microenvironment, adjusting their proliferation level to determine the rate of neurogenesis. Here we report that genetic deletion of neurofibromin (Nf1), a tumor suppressor with RAS-GAP activity, in adult NPCs enhanced DG proliferation and increased generation of new neurons in mice. Nf1 loss-associated neurogenesis had the functional effect of enhancing behavioral responses to subchronic antidepressants and, over time, led to spontaneous antidepressive-like behaviors. Thus, our findings establish an important role for the Nf1-Ras pathway in regulating adult hippocampal neurogenesis, and demonstrate that activation of adult NPCs is sufficient to modulate depression- and anxiety-like behaviors.
|Digital Object Identifier (DOI):||doi:10.1523/JNEUROSCI.3469-11.2012|
|Subjects:||Q Science > QH Natural history > QH426 Genetics|
|Divisions:||Faculty of Medicine > Human Development and Health
|Date Deposited:||20 Apr 2012 08:50|
|Last Modified:||27 Mar 2014 20:20|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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