Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system (CNS). A research project investigated the effects of acute and chronic ethanol exposure and withdrawal from chronic ethanol exposure on glymphatic function, a macroscopic waste clearance system that promotes efficient elimination of soluble proteins and metabolites from the central nervous system, including the proteins beta amyloid and tau that are associated with Alzheimer’s disease and other forms of dementia. Besides waste elimination, the glymphatic system also facilitates brain-wide distribution of several compounds, including glucose, lipids, amino acids, growth factors, and neuromodulators.
The research found that acute and chronic exposure to 1.5 g/kg (binge level) ethanol dramatically suppressed glymphatic function in awake mice. A significant increase in Glial fibrillary acidic protein (GFAP) expression, a molecular marker for inflammation was observed, particularly in cells called astrocytes which are key regulators of the glymphatic system. The levels of several cytokines also decreased. In contrast, glymphatic function increased in mice treated with 0.5 g/kg (low dose) ethanol following acute exposure, as well as after one month of chronic exposure. Low doses of chronic ethanol intake were associated with a significant decrease in GFAP expression, with little change in the cytokine profile compared with the saline group.
These observations suggest that ethanol has a J-shaped effect on the glymphatic system whereby low doses of ethanol increase glymphatic function. Conversely, chronic heavy intake induced reactive gliosis and perturbed glymphatic function, which possibly may contribute to the higher risk of dementia observed in heavy drinkers. “Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system,” said Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study. “However, in this study we have shown for the first time that low doses of alcohol are potentially beneficial to brain health, namely it improves the brain’s ability to remove waste.” Source: Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function. Lundgaard I, Wang W, Eberhardt A, Vinitsky HS, Reeves BC, Peng S, Lou N, Hussain R, Nedergaard M. Sci Rep. 2018 Feb 2;8(1):2246.