Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus

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Sairanen , M , Lucas , G , Ernfors , P , Castrén , M & Castren , E 2005 , ' Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus ' , Journal of Neuroscience , vol. 25 , no. 5 , pp. 1089-1094 . https://doi.org/10.1523/JNEUROSCI.3741-04.2005

Title: Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus
Author: Sairanen, Mikko; Lucas, Guilherme; Ernfors, Patrik; Castrén, Maija; Castren, Eero
Other contributor: University of Helsinki, Neuroscience center (-2009)
University of Helsinki, Neuroscience center (-2009)
University of Helsinki, Neuroscience center (-2009)
Date: 2005
Language: eng
Number of pages: 6
Belongs to series: Journal of Neuroscience
ISSN: 0270-6474
DOI: https://doi.org/10.1523/JNEUROSCI.3741-04.2005
URI: http://hdl.handle.net/10138/253842
Abstract: Antidepressants increase proliferation of neuronal progenitor cells and expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. We investigated the role of BDNF signaling in antidepressant-induced neurogenesis by using transgenic mice with either reduced BDNF levels (BDNF+/-) or impaired trkB activation (trkB.T1-overexpressing mice). In both transgenic strains, chronic (21 d) imipramine treatment increased the number of bromodeoxyuridine (BrdU)-positive cells to degree similar to that seen in wild-type mice 24 h after BrdU administration, although the basal proliferation rate was increased in both transgenic strains. Three weeks after BrdU administration and the last antidepressant injection, the amount of newborn (BrdU- or TUC-4-positive) cells was significantly reduced in both BDNF+/- and trkB.T1-overexpressing mice, which suggests that normal BDNF signaling is required for the long-term survival of newborn hippocampal neurons. Moreover, the antidepressant-induced increase in the surviving BrdU- positive neurons seen in wild-type mice 3 weeks after treatment was essentially lost in mice with reduced BDNF signaling. Furthermore, we observed that chronic treatment with imipramine or fluoxetine produced a temporally similar increase in both BrdU- positive and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeled neurons in the dentate gyrus, indicating that these drugs simultaneously increase both neurogenesis and neuronal elimination. These data suggest that antidepressants increase turnover of hippocampal neurons rather than neurogenesis per se and that BDNF signaling is required for the long-term survival of newborn neurons in mouse hippocampus.
Subject: 311 Basic medicine
118 Biological sciences
515 Psychology
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