Expression and dendritic trafficking of BDNF-6 splice variant are impaired in knock-in mice carrying human BDNF Val66Met polymorphism (original) (raw)

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2015

Abstract

The human Val66Met polymorphism in brain-derived neurotrophic factor (BDNF), a key factor in neuroplasticity, synaptic function and cognition, has been implicated in pathophysiology of neuropsychiatric and neurodegenerative disorders. BDNF is encoded by multiple transcripts with distinct regulation and localization, but the impact of the Val66Met polymorphism on BDNF regulation remains unclear. In BDNF Val66Met knock-in mice, which recapitulate the phenotypic hallmarks of individuals carrying the BDNF(Met) allele, we measured expression levels, epigenetic changes at promoters, and dendritic trafficking of distinct BDNF transcripts, using quantitative PCR, chromatin immunoprecipitation (ChIP), and in situ hybridization. BDNF-4 and BDNF-6 transcripts were reduced in BDNF(Met/Met) mice, compared with BDNF(Val/Val) mice. Chromatin immunoprecipitations for acetyl-histone H3 (acH3), a marker of active gene transcription, and trimethyl-histone-H3-Lys27 (H3K27me3), a marker of gene repressi...

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