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TitleRegulation of impulsive and aggressive behaviours by a novel lncRNA.
Publication TypeJournal Article
Year of Publication2020
AuthorsLabonté, Benoit, Khaled Abdallah, Gilles Maussion, Volodymyr Yerko, Jennie Yang, Thibault Bittar, Francis Quessy, Sam A. Golden, Luis Navarro, Dave Checknita, Carolina Gigek, Juan Pablo Lopez, Rachael L. Neve, Scott J. Russo, Richard E. Tremblay, Gilles Côté, Michael J. Meaney, Naguib Mechawar, Eric J. Nestler, and Gustavo Turecki
JournalMol Psychiatry
Date Published2020 Jan 06
ISSN1476-5578
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.

DOI10.1038/s41380-019-0637-4
Alternate JournalMol Psychiatry
PubMed ID31907380
PubMed Central IDPMC7436429
Grant List268065 / / Fonds de Recherche du Québec - Santé (Fonds de la recherche en sante du Quebec) /
R00 DA045662 / DA / NIDA NIH HHS / United States
FDN148374 / / Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) /
ENP161427 / / Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) /
EGM141899 / / Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) /
P50 MH096890 / MH / NIMH NIH HHS / United States
R01 MH051399 / MH / NIMH NIH HHS / United States