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Publication : TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment.

First Author  Li Y Year  2008
Journal  Neuron Volume  59
Issue  3 Pages  399-412
PubMed ID  18701066 Mgi Jnum  J:147252
Mgi Id  MGI:3839739 Doi  10.1016/j.neuron.2008.06.023
Citation  Li Y, et al. (2008) TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59(3):399-412
abstractText  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.
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