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Mol Psychiatry. 2020 Jan 6. doi: 10.1038/s41380-019-0637-4. [Epub ahead of print]

Regulation of impulsive and aggressive behaviours by a novel lncRNA.

Author information

1
Centre de Recherche CERVO, Department of Neuroscience and Psychiatry, Laval University, 2601, Chemin de la Canardière, Québec, QC, G1J 2G3, Canada. benoit.labonte@fmed.ulaval.ca.
2
Centre de Recherche CERVO, Department of Neuroscience and Psychiatry, Laval University, 2601, Chemin de la Canardière, Québec, QC, G1J 2G3, Canada.
3
McGill Group for Suicide Studies, Douglas Research Centre, Department of Psychiatry, McGill University, Frank B. Common Pavilion, 6875 LaSalle Blvd., Montreal, QC, H4H 1R3, Canada.
4
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5
Unitat de Genètica Molecular Institut de Biomedicina de València, Valencia, Spain.
6
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
7
Research Unit on Children's Psychosocial Maladjustment, Université de Montréal, Montreal, QC, Canada.
8
Philippe-Pinel Institute of Montreal, University of Montreal, Montreal, QC, Canada.
9
Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montreal, QC, Canada.
10
McGill Group for Suicide Studies, Douglas Research Centre, Department of Psychiatry, McGill University, Frank B. Common Pavilion, 6875 LaSalle Blvd., Montreal, QC, H4H 1R3, Canada. gustavo.turecki@mcgill.ca.

Abstract

High impulsive and aggressive traits associate with poor behavioural self-control. Despite their importance in predicting behavioural negative outcomes including suicide, the molecular mechanisms underlying the expression of impulsive and aggressive traits remain poorly understood. Here, we identified and characterized a novel long noncoding RNA (lncRNA), acting as a regulator of the monoamine oxidase A (MAOA) gene in the brain, and named it MAOA-associated lncRNA (MAALIN). Our results show that in the brain of suicide completers, MAALIN is regulated by a combination of epigenetic mechanisms including DNA methylation and chromatin modifications. Elevated MAALIN in the dentate gyrus of impulsive-aggressive suicides was associated with lower MAOA expression. Viral overexpression of MAALIN in neuroprogenitor cells decreased MAOA expression while CRISPR-mediated knock out resulted in elevated MAOA expression. Using viral-mediated gene transfer, we confirmed that MAALIN in the hippocampus significantly decreases MAOA expression and exacerbates the expression of impulsive-aggressive behavioural traits in CD1 aggressive mice. Overall, our findings suggest that variations in DNA methylation mediate the differential expression of a novel lncRNA that acts on MAOA expression to regulate impulsive-aggressive behaviours.

PMID:
31907380
DOI:
10.1038/s41380-019-0637-4

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