An ADAR1 inducer attenuated the effects of social isolation on depressive-like behavior and ADAR1 (p110) in BALB/c mice

Introduction: Social isolation induces depressive-like behavior in animals and humans by impacting RNA editing, but the detailed mechanisms are still unknown. The purpose of this study was to explore how an ADAR1 (RNA-editing enzyme) inducer and inhibitor may impact the isolation-induced depressive-like behavior of mice and to identify new therapeutic targets for the development of an effective solution for the recovery from depressive-like behavior in socially isolated animals and humans. Methods: Twenty-one-day-old BALB/c mice with and without isolation treatment were evaluated for depressive-like behavior by open-field tests, tail suspension tests, and forced swimming tests. Immunohistochemistry and Western blots were used to measure the immunoreactivity and protein expression of ADAR1 (p110). In addition, the isolated mice were treated with an ADAR1 inducer (IFN-γ) or inhibitor (EHNA). The performance of both treatments on the behavior of and ADAR1 (p110) expression in isolated mice was examined. Results: Both the immunoreactivity and protein expression of ADAR1 (p110) in the prefrontal cortex decreased in isolated BALB/c mice with depressive-like behavior compared to those of the age-matched, gregarious BALB/c mice. Additionally, the treatments with ADAR1 inducer or inhibitor improved or aggravated depressive-like behavior in isolated mice, respectively. Furthermore, the ADAR1 inducer returned the immunoreactivity and protein expression of ADAR1 (p110) back to the normal level. Conclusion: The ADAR1 inducer attenuated the effects of social isolation on depressive-like behavior and ADAR1 (p110) in BALB/c mice.