title: Neurofibromin modulates adult hippocampal neurogenesis and behavioral effects of antidepressants.
abstract: 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.
authors.affiliation: Department of Developmental Biology and Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Yanjiao
authors.initials: Y
authors.lastname: Li
authors.forename: Renée M
authors.initials: RM
authors.lastname: McKay
authors.forename: Dieter
authors.initials: D
authors.lastname: Riethmacher
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
mesh_terms: D000367:Age Factors; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000473:pathology; D002478:Cells, Cultured; D003863:Depression / Q000188:drug therapy* / Q000473:pathology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D025542:Neurofibromin 1 / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D025542:Neurofibromin 1