Transcriptome and chromatin alterations in social fear indicate association of MEG3 with successful extinction of fear.
Melanie RoyerBalagopal PaiRohit MenonAnna BludauKatharina GryksaRotem Ben-Tov PerryIgor UlitskyGunter MeisterInga D NeumannPublished in: Molecular psychiatry (2022)
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.
Keyphrases
- gene expression
- healthcare
- mental health
- long non coding rna
- pi k akt
- signaling pathway
- genome wide
- prefrontal cortex
- cell proliferation
- transcription factor
- dna damage
- primary care
- adipose tissue
- type diabetes
- multiple sclerosis
- resting state
- cell death
- oxidative stress
- ejection fraction
- chronic kidney disease
- cancer therapy
- long noncoding rna
- insulin resistance