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

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Reduced Brd1 expression leads to reversible depression-like behaviors and gene-expression changes in female mice. / Rajkumar, Anto P; Qvist, Per; Donskov, Julie G; Lazarus, Ross; Pallesen, Jonatan; Nava, Nicoletta; Winther, Gudrun; Liebenberg, Nico; Cour, Sanne H la; Paternoster, Veerle; Fryland, Tue; Palmfeldt, Johan; Fejgin, Kim; Mørk, Arne; Nyegaard, Mette; Pakkenberg, Bente; Didriksen, Michael; Nyengaard, Jens R; Wegener, Gregers; Mors, Ole; Christensen, Jane H; Børglum, Anders D.

I: Translational Psychiatry, Bind 10, 239, 07.2020.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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Rajkumar, Anto P ; Qvist, Per ; Donskov, Julie G ; Lazarus, Ross ; Pallesen, Jonatan ; Nava, Nicoletta ; Winther, Gudrun ; Liebenberg, Nico ; Cour, Sanne H la ; Paternoster, Veerle ; Fryland, Tue ; Palmfeldt, Johan ; Fejgin, Kim ; Mørk, Arne ; Nyegaard, Mette ; Pakkenberg, Bente ; Didriksen, Michael ; Nyengaard, Jens R ; Wegener, Gregers ; Mors, Ole ; Christensen, Jane H ; Børglum, Anders D. / Reduced Brd1 expression leads to reversible depression-like behaviors and gene-expression changes in female mice. I: Translational Psychiatry. 2020 ; Bind 10.

Bibtex

@article{e0cee56868ad49fbac68498def17680d,
title = "Reduced Brd1 expression leads to reversible depression-like behaviors and gene-expression changes in female mice",
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-, GPCR-, cAMP-, and CREB/CREM-signaling'. Integrative gene expression analysis specifically links changes in amygdaloid intracellular signaling activity to the behavioral treatment response in Brd1+/- mice. Collectively, our study highlights the importance of BRD1 as a modulator of affective pathology and adds to our understanding of the molecular mechanisms underlying affective disorders and their treatment response.",
author = "Rajkumar, {Anto P} and Per Qvist and Donskov, {Julie G} and Ross Lazarus and Jonatan Pallesen and Nicoletta Nava and Gudrun Winther and Nico Liebenberg and Cour, {Sanne H la} and Veerle Paternoster and Tue Fryland and Johan Palmfeldt and Kim Fejgin and Arne M{\o}rk and Mette Nyegaard and Bente Pakkenberg and Michael Didriksen and Nyengaard, {Jens R} and Gregers Wegener and Ole Mors and Christensen, {Jane H} and B{\o}rglum, {Anders D}",
year = "2020",
month = jul,
doi = "10.1038/s41398-020-00914-2",
language = "English",
volume = "10",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Reduced Brd1 expression leads to reversible depression-like behaviors and gene-expression changes in female mice

AU - Rajkumar, Anto P

AU - Qvist, Per

AU - Donskov, Julie G

AU - Lazarus, Ross

AU - Pallesen, Jonatan

AU - Nava, Nicoletta

AU - Winther, Gudrun

AU - Liebenberg, Nico

AU - Cour, Sanne H la

AU - Paternoster, Veerle

AU - Fryland, Tue

AU - Palmfeldt, Johan

AU - Fejgin, Kim

AU - Mørk, Arne

AU - Nyegaard, Mette

AU - Pakkenberg, Bente

AU - Didriksen, Michael

AU - Nyengaard, Jens R

AU - Wegener, Gregers

AU - Mors, Ole

AU - Christensen, Jane H

AU - Børglum, Anders D

PY - 2020/7

Y1 - 2020/7

N2 - 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-, GPCR-, cAMP-, and CREB/CREM-signaling'. Integrative gene expression analysis specifically links changes in amygdaloid intracellular signaling activity to the behavioral treatment response in Brd1+/- mice. Collectively, our study highlights the importance of BRD1 as a modulator of affective pathology and adds to our understanding of the molecular mechanisms underlying affective disorders and their treatment response.

AB - 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-, GPCR-, cAMP-, and CREB/CREM-signaling'. Integrative gene expression analysis specifically links changes in amygdaloid intracellular signaling activity to the behavioral treatment response in Brd1+/- mice. Collectively, our study highlights the importance of BRD1 as a modulator of affective pathology and adds to our understanding of the molecular mechanisms underlying affective disorders and their treatment response.

U2 - 10.1038/s41398-020-00914-2

DO - 10.1038/s41398-020-00914-2

M3 - Journal article

C2 - 32681022

VL - 10

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

M1 - 239

ER -