Reduced Brd1 expression leads to reversible depression-like behaviors and gene-expression changes in female mice.

Translational Psychiatry
Anto P RajkumarAnders D Børglum

Abstract

The schizophrenia-associated gene, BRD1, encodes an epigenetic regulator in which chromatin interactome is enriched with genes implicated in mental health. Alterations in histone modifications and epigenetic regulation contribute to brain transcriptomic changes in affective disorders and preclinical data supports a role for BRD1 in psychopathology. However, the implication of BRD1 on affective pathology remains poorly understood. In this study, we assess affective behaviors and associated neurobiology in Brd1+/- mice along with their responses to Fluoxetine and Imipramine. This involves behavioral, neurostructural, and neurochemical characterizations along with regional cerebral gene expression profiling combined with integrative functional genomic analyses. We report behavioral changes in female Brd1+/- mice with translational value to depressive symptomatology that can be alleviated by the administration of antidepressant medications. Behavioral changes are accompanied by altered brain morphometry and imbalances in monoaminergic systems. In accordance, gene expression changes across brain tissues reveal altered neurotransmitter signaling and cluster in functional pathways associated with depression including 'Adrenergic-, GPC...Continue Reading

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Methods Mentioned

BETA
acetylation
histone acetylation
dissection
FCS

Key Resources (RRID) Mentioned

MMRRC_065563

Software Mentioned

Imaris
GraphPad Prism
edgeR3
ingenuity pathway analysis ( IPA )
Ingenuity Pathway Analysis
STATA
newCAST
HISAT2
IPA
StringTie

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