α-Synuclein expression in the brain and blood during abstinence from chronic alcohol drinking in mice

Abstract

α-Synuclein is a presynaptic protein proposed to serve as a negative regulator of dopaminergic neurotransmission. Recent research has implicated α-synuclein in chronic neuroadaptations produced by psychostimulant and opiate use, as well as in genetically determined susceptibility to alcoholism in humans. The aim of our study was to characterize the changes in α-synuclein expression after short-term abstinence from chronic alcohol drinking in mice. Male C57BL/6J mice were allowed to drink increasing concentrations of alcohol in the two-bottle choice procedure. Then the mice were given constant access to an 8% alcohol solution and water for 32 days, and were sacrificed 2 h, 24 h or 48 h after alcohol withdrawal. RT-PCR, in situ hybridization and Western blotting techniques were used to measure α-synuclein mRNA and protein levels in the brain and blood. α-Synuclein protein levels were elevated by up to 80% in the amygdala of mice withdrawn from alcohol for 24 h or 48 h. No changes in α-synuclein levels were found in the mesencephalon or striatum/accumbens. The levels of α-synuclein mRNA remained unchanged in all brain regions examined (the striatum, nucleus accumbens, amygdala, substantia nigra, ventral tegmental area). α-Synuclein mRNA was up-regulated in the whole blood 48 h after alcohol withdrawal. The accumulation of α-synuclein in the amygdala, observed in this study, seems to be a common feature of alcohol and opiate abstinence. This finding suggests a role of α-synuclein in common neuroadaptations produced by long-term alcohol and drug use. Although α-synuclein expression in the blood seems unrelated to that in the brain, it may serve as a peripheral biomarker of chronic alcohol consumption.