MicroRNA-206 Regulates Stress-Provoked Aggressive Behaviors in Post-weaning Social Isolation Mice

• Published in: Molecular therapy. Nucleic acids Vol. 20; pp. 812 - 822
• Main Authors: Chang, Chih-Hua, Kuek, Elizabeth Joo Wen, Su, Chun-Lin, Gean, Po-Wu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.06.2020; American Society of Gene & Cell Therapy; Elsevier
• Subjects: aggression; AM206; antagomir; BDNF; epigenetics; intranasal; microRNA; miR-206; social isolation; ventral hippocampus; social isolation; antagomir; ventral hippocampus; BDNF; microRNA; intranasal; aggression; AM206; miR-206; epigenetics
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2020.05.001

When facing stressful conditions, some people tend to be impulsively aggressive whereas others are not. However, the causes and underlying mechanisms remain elusive. It has been reported that acute stress induces outbursts of aggression in post-weaning social isolation (SI) mice but not in group housing (GH) mice. Here we report epigenetic regulation of impulsive aggression in SI mice. At post-natal day 21, mice were randomly assigned to GH or SI groups. We found that SI mice exhibited a higher level of microRNA 206 (miR-206) compared with GH mice. Intra-hippocampal injection of AM206, an antagomir of miR-206, decreased stress-induced attack behavior in SI mice and increased BDNF expression. Moreover, BDNF expression was required for AM206 effects on the reduction of aggression. On the other hand, miR-206 overexpression in GH mice induced attack behavior. Intranasal administration of AM206 rather than a scramble control significantly reduced attack behavior and depression-like behavior in SI mice. Our results suggest that miR-206 mediates development of maladaptive impulsive aggression in early life adversity and that its antagomir could potentially be a therapeutic target against stress-exacerbated aggressive behavior. [Display omitted] miR-206 is known to regulate skeletal muscle development. Chang et al. showed that socially isolated mice exhibited higher levels of miR-206 and aggressive behavior. Intranasal administration of miR-206 antagomir significantly reduced attack behavior in social isolation mice. miR-206 is a potential therapeutic target for impulsive aggression.