The neuroimmune system - Where aging and excess alcohol intersect.

As the percentage of the global population over age 65 grows, and with it a subpopulation of individuals with alcohol use disorder (AUD), understanding the effect of alcohol on the aged brain is of utmost importance. Neuroinflammation is implicated in both natural aging as well as alcohol use, and its role in alterations to brain morphology and function may be exacerbated in aging individuals who drink alcohol to excess. The neuroimmune response to alcohol in aging is complex. The few studies investigating this issue have reported heightened basal activity and either hypo- or hyper-reactivity to an alcohol challenge. This review of preclinical research will first introduce key players of the immune system, then explore changes in neuroimmune function with aging or alcohol alone, with discussion of vulnerable brain regions, changes in cytokines, and varied reactions of microglia and astrocytes. We will then consider different levels of alcohol exposure, relevant animal models of AUD, and neuroimmune activation by alcohol across the lifespan. By identifying key findings, challenges, and targets for future research, we hope to bring more attention and resources to this underexplored area of inquiry.