TrKB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment (Neuron, 2008, 59:399-412)

報告日期: 2008/11/28
報告時間: 15:10/16:00
報告學生: 蕭雅心
講評老師: 黃阿敏

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 and Luis F. Parada 


 Neuron 59: 399-412 (2008)


Speaker: Hsiao, Ya-Hsin 

Commentator: Dr. Huang, A-Min

Time: 2008/11/28 15:10~16:00

Place: Room 602



Depression is a significant public health problem. Depressed patients usually require chronic antidepressant (AD) administration for weeks to months to achieve the goal. Previous reports indicate that delayed response to ADs is the increased production of new neurons in the dentate gyrus (DG). Exercise such as running also induces increased production of neurons. ADs or exercise enhances proliferation of neuronal progenitor cells (NPCs) in the subgranular zone (SGZ) of the DG. Brain-derived neurotrophic factor (BDNF) level in the hippocampus is increased by chronic, but not acute, AD exposure. Therefore, this study unveils whether BDNF acts directly on NPCs in vivo, and whether its effects on NPCs contribute to the overall influence of BDNF on AD response. Using in situ hybridization analysis and fluorescent-activated cell sorting (FACS), the authors demonstrated that TrkB, the high-affinity receptor for BDNF, is expressed in hippocampal NPCs. The authors generated trkB gene knockout in a cell-specific manner by crossing mice harboring the trkB floxed allele with transgenic mice expressing Cre recombinase under the human GFAP (hGFAP) promoter, or Synapsin I (Syn). The TrkBhGFAP, but not the TrkBSyn, ablation of TrkB in NPCs impairs DG morphogenesis, proliferation and neurogenesis. The authors found that TrkB expression in NPCs was required for ADs- and voluntary exercise-induced proliferation and neurogenesis. Next they indicated that TrkBhGFAP mice were insensitive to chronic-AD- and exercise-induced improvement in depression- and anxiety-like behaviors. The authors utilized tamoxifen inducible system to specific ablation of TrkB in adult NPCs and found that is sufficient to block sensitivity to ADs. These findings highlight the presence of TrkB in hippocampal neural progenitor cells is required for the neurogenic and behavioral actions of antidepressant treatments.



1. B.W. Luikart, S. Nef, T. Virmani, M.E. Lush, Y. Liu, E.T. Kavalali and L.F. Parada, TrkB has a cell-autonomous role in the establishment of hippocampal Schaffer collateral synapses, J. Neurosci. 25 : 3774-3786 (2005).