TY - JOUR
T1 - Neurofibromin Modulates Adult hippocampal neurogenesis and behavioral effects of antidepressants
AU - Li, Yun
AU - Li, Yanjiao
AU - McKay, Renée M.
AU - Riethmacher, Dieter
AU - Parada, Luis F.
PY - 2012/3/7
Y1 - 2012/3/7
N2 - 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 enhancedDGproliferation 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.
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 enhancedDGproliferation 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.
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U2 - 10.1523/JNEUROSCI.3469-11.2012
DO - 10.1523/JNEUROSCI.3469-11.2012
M3 - Article
C2 - 22399775
AN - SCOPUS:84863249752
SN - 0270-6474
VL - 32
SP - 3529
EP - 3539
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 10
ER -