Myelin Transcription Factor 1 (MyT1) overexpression mitigates social isolation-induced behavioral deficits: Insights into cortical synaptotagmin 1 regulation and antidepressant-like effects.

Abstract

Social isolation (SI) stress is increasingly recognized as a concern, associated with detrimental effects on mood and emotional well-being. Myelin Transcription Factor 1 (MyT1) is known for its pivotal role in nervous system development and mood regulation. This study delves into the potential of MyT1 to mitigate SI-induced behavioral abnormalities in mice. Utilizing a chronic SI model involving neonatal and post-weaning SI, male and female mice were subjected to lentiviral overexpression of MyT1 specifically in the medial prefrontal cortex (mPFC). A battery of behavioral assessments, including novelty-suppressed feeding, sucrose preference, sucrose splash, tape grooming, tail suspension, and forced swim tests, revealed notable antidepressant-like effects in both sexes upon MyT1 overexpression. Enhanced MyT1 expression corresponded with increased feeding initiation, sucrose preference, and self-grooming, alongside decreased immobility time. Importantly, the upregulation of MyT1 was accompanied by a significant reduction in cortical synaptotagmin 1 (Syt1) level. These findings underscore the involvement of MyT1 in mitigating SI-induced depression-like behavior. Moreover, the observed alterations in behavior are closely associated with changes in cortical Syt1 expression, suggesting its potential role as a target for unraveling the molecular mechanisms underlying mood disorders induced by SI. This study sheds light on the intricate interplay between MyT1 and cortical function in modulating responses to SI, paving the way for potential therapeutic interventions targeting these pathways.