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PMID: 18701066 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment.

Neuron ·Vol. 59 ·No. 3 ·2008-08-14 ·Pages 399-412

Li Y, Luikart BW, Birnbaum S, Chen J, Kwon CH, Kernie SG, Bassel-Duby R, Parada LF

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.

MeSH Terms
Adult Stem Cells Animals Animals, Newborn Antidepressive Agents/pharmacology Behavior, Animal Brain-Derived Neurotrophic Factor/metabolism Cell Differentiation/drug effects Cell Proliferation/drug effects Enzyme-Linked Immunosorbent Assay/methods Estrogen Antagonists/pharmacology Flow Cytometry/methods Green Fluorescent Proteins/biosynthesis,genetics Hippocampus/cytology Intermediate Filament Proteins/genetics,metabolism Mice Mice, Transgenic Motor Activity/drug effects,genetics Nerve Tissue Proteins/genetics,metabolism Nestin Neurons/drug effects Receptor, trkB/deficiency,physiology Tamoxifen/pharmacology
Chemicals
Antidepressive Agents Brain-Derived Neurotrophic Factor Estrogen Antagonists Intermediate Filament Proteins Nerve Tissue Proteins Nes protein, mouse Nestin Tamoxifen Green Fluorescent Proteins Receptor, trkB
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Li Yun
Department of Developmental Biology, Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
Luikart Bryan W
Birnbaum Shari
Chen Jian
Kwon Chang-Hyuk
Kernie Steven G
Bassel-Duby Rhonda
Parada Luis F
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2008.06.023
Published
2008-08-14
Pages
399-412
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2655199
Subset
IM
Grants
NIMH NIH HHS · P50 MH066172 · United States
NINDS NIH HHS · R37 NS033199-08 · United States
NINDS NIH HHS · R37 NS033199-10 · United States
NINDS NIH HHS · R37 NS033199 · United States
NINDS NIH HHS · R37NS033199 · United States
NIMH NIH HHS · P50 MH066172-070002 · United States
NIMH NIH HHS · P50MH66172 · United States
NINDS NIH HHS · R37 NS033199-11 · United States
NICHD NIH HHS · K08 HD001470 · United States
NINDS NIH HHS · R37 NS033199-09 · United States
NIMH NIH HHS · P50 MH066172-060002 · United States
Corrections
ErratumIn
-
CommentIn
PMID: 18701059
External Links
PubMed source DOI: 10.1016/j.neuron.2008.06.023 PMC Full Text View journal details
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