Astrocyte alterations and dysfunction in alcohol use disorder: A comprehensive scoping review of clinical postmortem and preclinical evidence.

Abstract

Alcohol use disorder (AUD) is a prevalent mental health condition associated with numerous comorbidities and health complications. Astrocytes are vital glial cells that are essential in maintaining homeostasis and responding to injury. Dysregulation of astrocytic function has been implicated in various disorders, including AUD, but the specific effects of alcohol and AUD on astrocytes remain unclear. This scoping review synthesizes evidence on alterations in astrocyte morphology and astrocytic protein expression in AUD and preclinical models. Post-mortem investigations are limited to a few brain regions and report no overall changes in the astrocyte protein, glial fibrillary acidic protein (GFAP) in AUD. In preclinical models, GFAP levels are elevated, particularly following periods of alcohol abstinence. In contrast, morphological changes in astrocytes are minimal following periods of alcohol abstinence and most notable with continuous ethanol exposure. Overall, convincing evidence of classically reactive astrocytes is lacking across paradigms. This review also highlights the lack of clinical research and sex-based analyses in the field. Future work should focus on in vivo PET imaging and employ more comprehensive measures of astrocyte function in multiple brain regions. A better understanding of astrocytic involvement in AUD could inform future research and therapeutic interventions, ultimately alleviating the disorder's burden.