C-U RNA editing in the mouse brain under chronic social defeat stress

Abstract

Existing studies suggest that RNA editing is associated with stress, neurological diseases and psychiatric disorders. However, the role of C-U RNA editing in chronic social defeat stress (CSDS) remains unclear. The current study herein analyzed mRNA C-U editing in the brain ventral tegmental area (VTA), a key brain reward region, and its changes in mouse models of CSDS under emotional stress (ES) or physiological stress (PS) conditions compared to controls. Our results discovered and validated C-U editing at 16 198 high confidence editing sites in adult male mouse VTA. Among them, 48 sites showed differential RNA editing levels among the three groups. Principal component analysis revealed 51.78% contribution from principle component 1 (PC1) to the variance. In addition, there were 307, 223, and 301 sites repeatedly observed in intra-group samples in ES, PS and control groups, respectively, and which were enriched in different gene functions. Moreover, a key factor previously reported to be involved in stress, serum/glucocorticoid regulated kinase 1 (Sgk1) gene was specifically upregulated and its mRNA was also specifically edited in ES. These results demonstrate dynamic C-U RNA editing in the brain VTA of mouse models of CSDS, which further suggests that C-U RNA editing is a potential molecular mechanism related to CSDS.