Ethanol-induced white matter atrophy is associated with impaired expression of aspartyl-asparaginyl-β-hydroxylase (ASPH)‎ and notch signaling in an experimental rat model

Abstract EN

Background.

Alcohol-induced white matter (WM) degeneration is linked to cognitive-motor deficits and impaired insulin/IGF and Notch networks that regulate oligodendrocyte function.

Ethanol also down-regulates expression of ASPH which drives Notch.

Objective.

Experiments were designed to determine if alcohol-related WM atrophy was linked to inhibition of ASPH and Notch.

Methods.

Adult Long Evans rats were fed for 3, 6, or 8 weeks with liquid diets containing 0% or 26% ethanol (caloric).

During the last 2 weeks of each endpoint, ethanol-exposed rats were binged with 2 g/kg ethanol, 3×/week.

Frontal lobe and cerebellar histological sections were used for image analysis and frontal WMwas used for protein studies.

Results.

Ethanol caused exposure duration-dependent reductions in frontal and cerebellar WM content.

WM atrophy was associated with reduced expression of ASPH, Jagged-1, HES-1, and HIF-1α.

Conclusions.

These new findings link ethanol-induced WM atrophy to inhibition of ASPH expression and Notch network signaling, providing additional potential targets for treatment of alcoholic brain disease