MicroRNA-206 regulates stress-provoked aggressive behaviors in post-weaning social isolation mice

Abstract

When encountered acute stress the emotion state of socially isolated (SI) mice will culminate in aberrant expressions of defensive behaviors and induced outburst of attack behavior which was reminiscent of reactive-impulsive aggression in humans We have previously shown that brain derived neurotrophic factor (BDNF) within the ventral hippocampus (VHip) was critical for stress-provoked aggressive behaviors in the post-weaning social isolation mice However the causes and underlying mechanism of stress-provoked aggression remain elusive Here we investigated the epigenetic regulation of BDNF in the VH At postnatal day 21–28 mice were randomly assigned to a group or isolated cages for 5 weeks We found that the isolated (SI) mice exhibited a higher level of microRNA 206 (miR-206) compared to group housing (GH) mice Previous study has shown that miR-206 can regulate BDNF in transgenic mice of Alzheimer disease that was antagonized by AM206 in a dose-dependent manner Quantitative real-time PCR (qPCR) showed that intra-hippocampal injection of AM206 decreased SI-induced increase in miR-206 and attack numbers without affecting locomotion activity In parallel AM206 increased both mRNA and protein levels of BDNF Furthermore the results also demonstrated that after knockdown BDNF reversed the effects of AM206 in the SI mice but did not affect the GH mice Besides that by using lentivirus mimic miR-206 in the GH mice the results showed that overexpression miR-206 in the GH mice significantly increased the number of attacks compared with the control group Therefore our results suggest a potential therapeutic effect of AM206 against stress exacerbation of aggressive behaviors

Date of Award	2019
Original language	English
Supervisor	Po-Wu Gean (Supervisor)