title: Prior Binge Ethanol Exposure Potentiates the Microglial Response in a Model of Alcohol-Induced Neurodegeneration.
abstract: Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced neurodegeneration results in anti-inflammatory microglia, while intermittent exposure models with lower doses and blood alcohol levels produce microglia with a pro-inflammatory phenotype. To determine the effect of a repeated binge alcohol exposure, rats received two cycles of the four-day Majchrowicz model. One hemisphere was then used to assess microglia via immunohistochemistry and while the other was used for ELISAs of cytokines and growth factors. A single binge ethanol exposure resulted in low-level of microglial activation; however, a second binge potentiated the microglial response. Specifically, double binge rats had greater OX-42 immunoreactivity, increased ionized calcium-binding adapter molecule 1 (Iba-1+) cells, and upregulated tumor necrosis factor-α (TNF-α) compared with the single binge ethanol group. These data indicate that prior ethanol exposure potentiates a subsequent microglia response, which suggests that the initial exposure to alcohol primes microglia. In summary, repeated ethanol exposure, independent of other immune modulatory events, potentiates microglial activity.
authors.affiliation: Department of Psychology &amp; Neuroscience; University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA. simon.alexm@unc.edu.
authors.forename: Simon Alex
authors.initials: SA
authors.lastname: Marshall
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. chelsea.geil@uky.edu.
authors.forename: Chelsea Rhea
authors.initials: CR
authors.lastname: Geil
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. kim-nixon@uky.edu.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Nixon
keywords: TNF-alpha; alcohol; alcoholism; cytokines; ethanol; microglia; microglial priming; neurodegeneration