Neuroimmune signaling in alcohol use disorder.

Microglia-specific consequences of alcohol-induced neuroinflammation. Alcohol exposure generates a proinflammatory environment in brain, resulting in up-regulation of immune ligands such as cytokines and chemokines. This results in activation of immune receptors on microglia, persistent transcriptome changes, structural plasticity, and the production of several inflammatory mediators that can alter neuronal function.

Astrocyte-specific consequences of alcohol-induced neuroinflammation. Alcohol exposure generates a proinflammatory environment in brain, resulting in up-regulation of immune ligands such as cytokines and chemokines. This results in activation of immune receptors on astrocytes, leading to transcriptome changes which contribute to the modulation of several astrocyte functions, including glutamate homeostasis, calcium signaling, gap junction communication, structural plasticity, and the production of inflammatory mediators, which can alter neuronal function in various ways.

Potential neuroimmune-mediated mechanisms that underlie associations between psychiatric diseases including alcohol use disorder (AUD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). AUD, MDD, and PTSD are frequently comorbid. Environmental and biological factors that can influence and lead to neuroinflammation are associated with all three disorders. Sustained neuroimmune imbalance can lead to physiological consequences that drive behavioural phenotypes associated with psychiatric disease. Altered behavior may enhance further risk for neuroinflammation, resulting in a persistent cycle that leaves patients vulnerable to additional psychiatric disorders. Pharmacotherapies that target neuroinflammation are possible treatment options for comorbid psychiatric diseases with common neuroimmune elements.