Abstract
Adolescent binge drinking represents a major public health challenge and can lead to persistent neurological and mental conditions, but the underlying pathogenic mechanisms remain poorly understood. Using a mouse model of adolescent binge ethanol treatment (ABET), we found that this treatment induced behavioral changes associated with demyelination in different brain regions. After ABET, adolescent mice exhibited anxiogenic behaviors with no change in locomotion on the elevated plus maze, and impaired spatial memory indicated by a significant reduction in spontaneous alternation in the Y maze test. Both effects persisted into adulthood. Anatomical studies further showed that ABET induced a significant reduction of parvalbumin-positive (PV+) GABAergic interneurons and myelin density in the hippocampus and medial prefrontal cortex (mPFC). While these deficits in PV+ interneurons and myelin persisted into early adulthood in the hippocampus, the myelin density recovered in the mPFC. Moreover, whereas ABET mainly damaged myelin of PV+ axons in the hippocampus, it primarily damaged myelin of PV-negative axons in the mPFC. Thus, our findings reveal that an adolescent binge alcohol treatment regimen disrupts spatial working memory, increases anxiety-like behaviors, and exerts unique temporal and spatial patterns of gray matter demyelination in the hippocampus and mPFC.
Highlights
Binge drinking is defined by the National Institute on Alcohol Abuse and Alcoholism as “a pattern of drinking that brings blood alcohol concentration levels to 0.08 g/ dL”
adolescent binge ethanol treatment (ABET) induced anxiety-like behaviors that persisted into adulthood To determine behavioral and brain structural changes associated with adolescent alcohol binge drinking, we used an established mouse model of ABET [9] with some modifications (Fig. 1)
These findings reveal that ABET has no effect on locomotor activity in three distinct assays, and it does not change the center/parameter time ratio in the open field test, which differs from the Elevated plus maze (EPM) results
Summary
Binge drinking is defined by the National Institute on Alcohol Abuse and Alcoholism as “a pattern of drinking that brings blood alcohol concentration levels to 0.08 g/ dL”. Large population studies have found that, across the Alcohol binge drinking can be especially harmful in adolescents, since adolescence is a critical developmental period associated with maturation of cognitive ability, personality, and frontal cortical executive functions. This coincides with gray matter (GM) myelination in different brain regions, including the hippocampus and medial prefrontal cortex (mPFC). Different from white matter (WM) myelin that has been extensively studied, Rice et al Acta Neuropathologica Communications (2019) 7:173
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