ADOLESCENT BINGE DRINKING INDUCES BEHAVIORAL ABNORMALITIES IN ADULTHOOD CAUSED BY MYELIN ABNORMALITIES

Abstract Background Adolescent binge drinking represents a major public health challenge and lead to persistent psychiatric disorders. However, the underlying pathogenic mechanisms remain poorly understood. Myelin abnormalities were observed in human subjects with alcohol abuse. Aims & Objectives In the present study, we investigated whether myelin abnormalities are involved in behavioral abnormalities induced by adolescent binge ethanol treatment (ABET). Method To produce ABET, C57BL/6J mouse was given EtOH (3.0g/kg, i.g. 25% ethanol w/v) once a day during adolescence (P28-46) in an intermittent fashion. Results ABET persistently developed behavioral abnormalities such as anxiety-like behaviors in the marble burying test and the novelty suppressed feeding test, impaired memory function in the novel object recognition test, and impairment of social interaction. ABET decreased myelin-related protein and mature oligodendrocytes through impaired oligodendrogenesis in the prefrontal cortex and hippocampus. Inhibiting adolescent myelination by deletion of myelin regulatory factor (Myrf) in oligodendrocyte precursor cells increased susceptibility to behavioral abnormalities induced by a subthreshold ABET, while promoting oligodendrogenesis and myelination via clemastine treatment rescues the ABET-induced behavioral abnormalities. Discussion & Conclusion These findings suggest that myelin abnormalities caused by ABET may be involved in the behavioral abnormalities in adulthood.