Exploring the role of omega-3/omega-6 balance in long-lasting changes in microglia caused by intermittent alcohol consumption during adolescence

Alcohol raises concerns due to the episodic and intense alcohol intake observed in adolescents. Recent studies reveal a correlation between escalated EtOH intake and neuroinflammation, emphasizing the endocannabinoid (eCB) system´s engagement. Our previous data in mice revealed that intermittent EtOH-exposure during adolescence leads to elevated levels of the ω-6 arachidonic acid (AA) in adulthood. AA is intricately linked to the neuroinflammatory response as a precursor of proinflammatory prostaglandins, and its brain levels are intertwined with balance between the synthesis and hydrolysis of eCBs. Therefore, this study delves into the multifaceted neuroprotective potential of the ω-3 eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids, specifically focusing on their anti-inflammatory properties to mitigate brain damage induced by binge drinking. To this end, we used a 4-week drinking-in-the-dark procedure in male C57BL/6J mice, which were randomly assigned to H2O or EtOH groups, half of which received a ω-3 enriched diet (H2OΩ3 and EtOHΩ3) during a 2-week withdrawal period. Here, we further explored microglia as a critical component of the brain's innate immune response, showing that excessive alcohol consumption resulted in a poorer pattern of arborization. Semi-quantitative antibody array analysis of cytokine levels revealed a decrease in CX3CL1, with known key roles in synaptic plasticity and microglial responses to proinflammatory stimuli, through its interaction with the microglial receptor CX3CR1. Interestingly, the effects of binge drinking on microglial arborization and CX3CL1 expression were reversed by a ω-3 enriched diet, which may provide a non-pharmacological strategy to counteract deleterious effects caused by binge drinking.