Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function

Abstract

Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system (CNS). Here we investigated the effects of acute and chronic ethanol exposure and withdrawal from chronic ethanol exposure on glymphatic function, which is a brain-wide metabolite clearance system connected to the peripheral lymphatic system. Acute and chronic exposure to 1.5 g/kg (binge level) ethanol dramatically suppressed glymphatic function in awake mice. Chronic exposure to 1.5 g/kg ethanol increased GFAP expression and induced mislocation of the astrocyte-specific water channel aquaporin 4 (AQP4), but decreased the levels of several cytokines. Surprisingly, 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 1.5 g/kg ethanol intake induced reactive gliosis and perturbed glymphatic function, which possibly may contribute to the higher risk of dementia observed in heavy drinkers.

Subventricular zone neural precursor cell responses after traumatic brain injury and binge alcohol in male rats

“…Our group has shown that in a rat model of TBI and binge alcohol, recovery in a skilled sensorimotor task was slower and the recovery plateau was lower in alcohol-exposed animals (Vaagenes et al, 2015) as also reported in clinical studies (Corrigan, 1995;Gurney et al, 1992;Joseph et al, 2015;Schutte & Hanks, 2010) although others have found a benefit (Chandrasekar et al, 2018(Chandrasekar et al, , 2017Lundgaard et al, 2018).…”

“…The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines binge drinking as a mode of consumption that results in a BAL of greater than 80 mg/dl, which is typically achieved by having five drinks for men and four drinks for women in two hours (Olthuis, Zamboanga, Ham, & Tyne, ). Our group has shown that in a rat model of TBI and binge alcohol, recovery in a skilled sensorimotor task was slower and the recovery plateau was lower in alcohol‐exposed animals (Vaagenes et al, ) as also reported in clinical studies (Corrigan, ; Gurney et al, ; Joseph et al, ; Schutte & Hanks, ) although others have found a benefit (Chandrasekar et al, ; Lundgaard et al, ).…”

PDGF-B Is Required for Development of the Glymphatic System

“…The polarization of AQP4 along vessels in tissue was quantified in cortex and hippocampus ( Kress et al, 2014 ; Lundgaard et al, 2018 ). Blood vessels were selected at random on confocal images and marked cross-sectionally using the line plot tool in ImageJ to include AQP4 signal from vascular endfeet and from the surrounding parenchyma.…”

Relationship of Wine Consumption with Alzheimer’s Disease

“…The question of whether the APOE-4 allele influences the protective effect of moderate ethanol intake on cognitive risk has not yet been resolved [58]. A glymphatic system [67] formed by astroglial cells was discovered in the central nervous system, which may eliminate soluble proteins and metabolites and plays a key role in the clearance of proteins that are potentially neurotoxic, such as Aβ18 and Tau23. The effect of acute and chronic exposure to ethanol on glymphatic function was investigated.…”