Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain
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Date
2021-09-01
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Abstract
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.
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Funding Information: Funding: The present study was funded by Fundamental & Applied Research Projects (FLPP), Latvian Council of Science wide no. lzp-2020/2-0069 (The role of human herpesvirus-6 infection and alcohol abuse in the development of neuroinflammation). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords
Chronic alcoholism, HHV-6, Microglia, Neuroinflammation, Substantia Nigra, 3.3 Health sciences, 5.1 Psychology, 3.1 Basic medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, Medicine (miscellaneous), General Biochemistry,Genetics and Molecular Biology, SDG 3 - Good Health and Well-being
Citation
Jain, N, Smirnovs, M, Strojeva, S, Murovska, M & Skuja, S 2021, 'Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain', Biomedicines , vol. 9, no. 9, 1216. https://doi.org/10.3390/biomedicines9091216, https://doi.org/10.3390/biomedicines9091216