Royer, Melanie and Pai, Balagopal and Menon, Rohit and Bludau, Anna and Gryksa, Katharina and Perry, Rotem Ben-Tov and Ulitsky, Igor and Meister, Gunter and Neumann, Inga D. (2022) Transcriptome and chromatin alterations in social fear indicate association of MEG3 with successful extinction of fear. MOLECULAR PSYCHIATRY, 27 (10). pp. 4064-4076. ISSN 1359-4184, 1476-5578
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LONG NONCODING RNAS; PHOSPHATIDYLINOSITOL 3-KINASE; SYNAPTIC PLASTICITY; GENE-EXPRESSION; LATERAL SEPTUM; ANXIETY; OXYTOCIN; ACTIVATION; KINASE; PHARMACOTHERAPY; |
| Subjects: | 500 Science > 570 Life sciences 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann) Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Nov 2023 13:18 |
| Last Modified: | 14 Nov 2023 13:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56735 |
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