Evidence map›Paper›PMID 25023144›Full record

ArticleMolecular psychiatry2014

Epigenetic reprogramming of cortical neurons through alteration of dopaminergic circuits.

K Brami-Cherrier, A Anzalone, M Ramos, I Forne, F Macciardi, A Imhof, E Borrelli

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

K Brami-Cherrier1] Department of Microbiology and Molecular Genetics and INSERM/UCI U904, University of California Irvine, Irvine, CA, USA [2] Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, USA.ORCID 0000000230093821
A Anzalone1] Department of Microbiology and Molecular Genetics and INSERM/UCI U904, University of California Irvine, Irvine, CA, USA [2] Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, USA.
M Ramos1] Department of Microbiology and Molecular Genetics and INSERM/UCI U904, University of California Irvine, Irvine, CA, USA [2] Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, USA.
I ForneMunich Cluster for Systems Neurology (SyNergy) and Adolf-Butenandt Institute, Ludwig Maximilians University of Munich, Munich, Germany.
F Macciardi1] Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, USA [2] Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
A Imhof1] Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, USA [2] Munich Cluster for Systems Neurology (SyNergy) and Adolf-Butenandt Institute, Ludwig Maximilians University of Munich, Munich, Germany.
E Borrelli1] Department of Microbiology and Molecular Genetics and INSERM/UCI U904, University of California Irvine, Irvine, CA, USA [2] Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, USA.
University of California, Irvine · USMunich Cluster for Systems Neurology · DE

Funding

Presynaptic versus postsynaptic functions of dopamine D2 receptors in the responsR01DA024689 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BORRELLI, EMILIANA · 2008 to 2012
$1.7M
NIDA NIH HHS DA024689NIDA NIH HHS R01 DA024689
6 · The paper itself

Abstract

Alterations of the dopaminergic system are associated with the cognitive and functional dysfunctions that characterize complex neuropsychiatric disorders. We modeled a dysfunctional dopaminergic system using mice with targeted ablation of dopamine (DA) D2 autoreceptors in mesencephalic dopaminergic neurons. Loss of D2 autoreceptors abolishes D2-mediated control of DA synthesis and release. Here, we show that this mutation leads to a profound alteration of the genomic landscape of neurons receiving dopaminergic afferents at distal sites, specifically in the prefrontal cortex. Indeed, we observed a remarkable downregulation of gene expression in this area of ~2000 genes, which involves a widespread increase in the histone repressive mark H3K9me2/3. This reprogramming process is coupled to psychotic-like behaviors in the mutant mice. Importantly, chronic treatment with a DA agonist can revert the genomic phenotype. Thus, cortical neurons undergo a profound epigenetic reprogramming in response to dysfunctional D2 autoreceptor signaling leading to altered DA levels, a process that may underlie a number of neuropsychiatric disorders.

Indexed as

Epigenesis, GeneticAnimalsAutoreceptorsCorpus StriatumDopamineDopamine AgonistsDopaminergic NeuronsDown-RegulationGene ExpressionHistonesMice, TransgenicPrefrontal CortexPsychotic DisordersQuinpiroleReceptors, Dopamine D2AutoreceptorsDopamineDopamine AgonistsHistonesQuinpiroleReceptors, Dopamine D2

Identifiers

PMID25023144
PMCPMC4211954
OpenAlexW2043368060

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.