Transcriptome and Chromatin Alterations in Social Fear Indicate Association of MEG3 with Successful Extinction of Fear

Overview

Journal Mol Psychiatry

Specialties Molecular Biology
Psychiatry

Date 2022 Mar 26

PMID 35338311

Authors

Melanie Royer

Balagopal Pai

Rohit Menon

Anna Bludau

Katharina Gryksa

Rotem Ben-Tov Perry

Igor Ulitsky

Gunter Meister

Inga D Neumann

Affiliations

Soon will be listed here.

Abstract

Social anxiety disorder is characterized by a persistent fear and avoidance of social situations, but available treatment options are rather unspecific. Using an established mouse social fear conditioning (SFC) paradigm, we profiled gene expression and chromatin alterations after the acquisition and extinction of social fear within the septum, a brain region important for social fear and social behaviors. Here, we particularly focused on the successful versus unsuccessful outcome of social fear extinction training, which corresponds to treatment responsive versus resistant patients in the clinics. Validation of coding and non-coding RNAs revealed specific isoforms of the long non-coding RNA (lncRNA) Meg3 regulated, depending on the success of social fear extinction. Moreover, PI3K/AKT was differentially activated with extinction success in SFC-mice. In vivo knockdown of specific Meg3 isoforms increased baseline activity of PI3K/AKT signaling, and mildly delayed social fear extinction. Using ATAC-Seq and CUT&RUN, we found alterations in the chromatin structure of specific genes, which might be direct targets of lncRNA Meg3.

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