Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain

Both chronic alcoholism and human herpesvirus-6 (HHV-6) infection have been identified as promoters of neuroinflammation and known to cause movement-related disorders. Substantia Nigra (SN), the dopaminergic neuron-rich region of the basal ganglia, is involved in regulating motor function and the reward system. Hence, we hypothesize the presence of possible synergism between alcoholism and HHV-6 infection in the SN region and report a comprehensive quantification and characterization of microglial functions and morphology in postmortem brain tissue from 44 healthy, age-matched alcoholics and chronic alcoholics. A decrease in the perivascular CD68+ microglia in alcoholics was noted in both the gray and white matter. Additionally, the CD68+/Iba1- microglial subpopulation was found to be the dominant type in the controls. Conversely, in alcoholics, dystrophic changes in microglia were seen with a significant increase in Iba1 expression and perivascular to diffuse migration. An increase in CD11b expression was noted in alcoholics, with the Iba1+/CD11b- subtype promoting inflammation. All the controls were found to be negative for HHV-6 whilst the alcoholics demonstrated HHV-6 positivity in both gray and white matter. Amongst HHV-6 positive alcoholics, all the above-mentioned changes were found to be heightened when compared with HHV-6 negative alcoholics, thereby highlighting the compounding relationship between alcoholism and HHV-6 infection that promotes microglia-mediated neuroinflammation.

Automated summary

Chronic alcoholism and HHV-6 infection have been shown to promote neuroinflammation, especially in the Substantia Nigra (SN) region, resulting in significant changes in microglial functions and morphology. Alcoholics exhibit more inflammatory microglial changes and an increase in Iba1 expression, while HHV-6 infection exacerbates these effects. This highlights the compounding relationship between alcoholism and HHV-6 infection in promoting microglia-mediated neuroinflammation.