TrkB Regulates Hippocampal Neurogenesis and Governs Sensitivity to Antidepressive Treatment

Yun Li, Bryan W. Luikart, Shari Birnbaum, Jian Chen, Chang Hyuk Kwon, Steven G. Kernie, Rhonda Bassel-Duby, Luis F. Parada

Research output: Contribution to journalArticle

413 Scopus citations

Abstract

Adult hippocampal neurogenesis is stimulated by chronic administration of antidepressants (ADs) and by voluntary exercise. Neural progenitor cells (NPCs) in the dentate gyrus (DG) that are capable of continuous proliferation and neuronal differentiation are the source of such structural plasticity. Here we report that mice lacking the receptor tyrosine kinase TrkB in hippocampal NPCs have impaired proliferation and neurogenesis. When exposed to chronic ADs or wheel-running, no increase in proliferation or neurogenesis is observed. Ablation of TrkB also renders these mice behaviorally insensitive to antidepressive treatment in depression- and anxiety-like paradigms. In contrast, mice lacking TrkB only in differentiated DG neurons display typical neurogenesis and respond normally to chronic ADs. Thus, our data establish an essential cell-autonomous role for TrkB in regulating hippocampal neurogenesis and behavioral sensitivity to antidepressive treatments, and support the notion that impairment of the neurogenic niche is an etiological factor for refractory responses to an antidepressive regimen.

Original languageEnglish (US)
Pages (from-to)399-412
Number of pages14
JournalNeuron
Volume59
Issue number3
DOIs
StatePublished - Aug 14 2008

Keywords

  • DEVBIO
  • MOLNEURO
  • STEMCELL

ASJC Scopus subject areas

  • Neuroscience(all)

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