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Publication : Lack of promoter IV-driven BDNF transcription results in depression-like behavior.

First Author  Sakata K Year  2010
Journal  Genes Brain Behav Volume  9
Issue  7 Pages  712-21
PubMed ID  20528954 Mgi Jnum  J:178217
Mgi Id  MGI:5297687 Doi  10.1111/j.1601-183X.2010.00605.x
Citation  Sakata K, et al. (2010) Lack of promoter IV-driven BDNF transcription results in depression-like behavior. Genes Brain Behav 9(7):712-21
abstractText  Transcription of Bdnf is controlled by multiple promoters, in which promoter IV contributes significantly to activity-dependent Bdnf transcription. We have generated promoter IV mutant mice [brain-derived neurotrophic factor (BDNF)-KIV] in which promoter IV-driven expression of BDNF is selectively disrupted by inserting a green fluorescent protein (GFP)-STOP cassette within the Bdnf exon IV locus. BDNF-KIV animals exhibited depression-like behavior as shown by the tail suspension test (TST), sucrose preference test (SPT) and learned helplessness test (LHT). In addition, BDNF-KIV mice showed reduced activity in the open field test (OFT) and reduced food intake in the novelty-suppressed feeding test (NSFT). The mutant mice did not display anxiety-like behavior in the light and dark box test and elevated plus maze tests. Interestingly, the mutant mice showed defective response inhibition in the passive avoidance test (PAT) even though their learning ability was intact when measured with the active avoidance test (AAT). These results suggest that promoter IV-dependent BDNF expression plays a critical role in the control of mood-related behaviors. This is the first study that directly addressed the effects of endogenous promoter-driven expression of BDNF in depression-like behavior.
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