RT Journal Article
SR Electronic
T1 Neurofibromin Modulates Adult Hippocampal Neurogenesis and Behavioral Effects of Antidepressants
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3529
OP 3539
DO 10.1523/JNEUROSCI.3469-11.2012
VO 32
IS 10
A1 Li, Yun
A1 Li, Yanjiao
A1 McKay, Renée M.
A1 Riethmacher, Dieter
A1 Parada, Luis F.
YR 2012
UL http://www.jneurosci.org/content/32/10/3529.abstract
AB 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.