Microglia are the primary immune cell in the central nervous system and are known as the “resident” macrophages in the central nervous system (CNS). While microglia are classically known as the immune cells of the CNS, their role has more recently been shown to extend far beyond immunity. The effects of ethanol on the brain are closely linked to neuroimmune responses mediated by microglia that are present in the healthy brain from the time of development. Though microglia have been classified as the “resident” immune cells of the CNS, new research suggests that other immune cells may be implicated in the immune response. Normally, the blood-brain barrier (BBB) prevents the infiltration of cells and foreign pathogens from crossing from the periphery into the CNS. However, peripheral monocytes are known to infiltrate the CNS in response to seizures, traumatic brain injury, infection, and multiple sclerosis. Whether or not these cells engraft and become microglia is still a topic of debate. The aim of this study was to determine the effect of acute ethanol on microglia activation and monocyte infiltration into the CNS. We hypothesized that acute EtOH would lead to an increase in neuroinflammation by activating “resident” microglia to an inflammatory polarization and induce the infiltration of macrophages across the BBB. Using the Macrophage FAS-Induced Apoptosis (MaFIA) mouse model (GFP+ on Csf1r promoter), fluorescent microscopy, and flow cytometry we assessed the presence and phenotype of microglia and infiltrating macrophages following 1, 2, and 4 g/kg ethanol at .5, 1, and 2 hours post-injection. By measuring volume/surface area of microglia in the VTA and NAc following EtOH, we found that EtOH caused microglia activation in these areas, and that the microglia are shifting toward an M1 polarization. However, some of our findings were counter to our hypothesis. We found that EtOH, decreases the number of infiltrating monocytes in the VTA and NAc. It is possible that other cells like T and B cells are recruited across the BBB. These findings suggest a neuroimmune connection for acute ethanol use and challenge the dogma that ethanol has exclusively central effects on DA neuronal activity and release. Further research is being performed to examine the implications of this effect, and what effects a conditional knockdown of monocytes has on ethanol intoxication and reward.
College and Department
BYU ScholarsArchive Citation
Clarke, Travis Jonathan, "Neuroimmune-Mediated Alcohol Effects on Ventral Tegmental Area Microglia and Infiltrating Leukocytes" (2018). Theses and Dissertations. 7566.
alcohol, microglia, macrophage, inflammation, cytokines, neuroimmune