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

Kazuko Sakata, L. Jin, S. Jha

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)712-721
Number of pages10
JournalGenes, Brain and Behavior
Volume9
Issue number7
DOIs
StatePublished - Oct 1 2010

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Brain-Derived Neurotrophic Factor
Depression
Learned Helplessness
Hindlimb Suspension
Aptitude
Green Fluorescent Proteins
Sucrose
Exons
Anxiety
Eating
Learning
Light

All Science Journal Classification (ASJC) codes

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Lack of promoter IV-driven BDNF transcription results in depression-like behavior. / Sakata, Kazuko; Jin, L.; Jha, S.

In: Genes, Brain and Behavior, Vol. 9, No. 7, 01.10.2010, p. 712-721.

Research output: Contribution to journalArticle

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