Its complicated: The relationship between alcohol and microglia in the search for novel pharmacotherapeutic targets for alcohol use disorders

Abstract

Alcohol use disorder (AUD) is a chronic relapsing disorder with wide-ranging health consequences. Alcohol targets the central nervous system producing neurodegeneration and subsequent cognitive and behavioral deficits, but the mechanisms behind these effects remain unclear. Recently, evidence has been mounting for the role of neuroimmune activation in the pathogenesis of AUDs, but our nascent state of knowledge about the interaction of alcohol with the neuroimmune system supports that the relationship is complicated. As the resident macrophage of the central nervous system, microglia are a central focus. Human and animal research on the interplay between microglia and alcohol in AUDs has proven to be complex, and though early research focused on a pro-inflammatory phenotype of microglia, the anti-inflammatory and homeostatic roles of microglia must be considered. How these new roles for microglia should be incorporated into our thinking about the neuroimmune system in AUDs is discussed in the context of developing novel pharmacotherapies for AUDs.

Keywords: Alcohol; Alcoholism; Drug discovery; Ethanol; Microglia; Neurodegeneration; Neuroimmune; Neuroinflammation.