THE CONTRIBUTION OF CEREBRAL VASCULATURE AND METABOLIC REGULATION TO MYELIN ALTERATIONS ASSOCIATED WITH ADOLESCENT ALCOHOL ABUSE

Alcohol addiction frequently begins during adolescence, a critical period for brain maturation, leading to persistent neurobiological and behavioral alterations that promote addiction. Chronic alcohol consumption is associated with reduced cerebral blood flow and metabolic activity, processes essential for myelination, yet the relationship between alcohol-induced vascular and myelin alterations and subsequent functional impairments remains poorly understood. This study aimed to investigate the effects of adolescent alcohol exposure on myelin integrity and cerebrovascular markers in key brain regions. Male Wistar rats were subjected to intermittent ethanol administration during adolescence. Brain tissue from the hippocampus and medial prefrontal cortex was collected 24 hours and 2 weeks after the last exposure. Immunohistochemistry for myelin basic protein, oligodendrocytes, and endothelial markers was combined with fluorescent imaging, molecular analyses of protein and RNA expression, and magnetic resonance approaches to assess metabolic and white matter changes. In the hippocampus, alcohol exposure increased myelinated fiber density while reducing myelin basic protein immunoreactivity at 24 hours, effects that normalized after 2 weeks; vascular density was unchanged, but reduced Glut-1 intensity suggested metabolic dysregulation. In contrast, the medial prefrontal cortex showed delayed effects, with reduced oligodendrocyte density at 2 weeks despite preserved myelin organization, indicating compensatory mechanisms. Overall, adolescent alcohol exposure induces region- and time-dependent alterations in myelin and vascular function, providing insight into mechanisms that may underlie alcohol-related cognitive and behavioral deficits.

This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project "PI22-01141" and co-funded by the European Union.