Alcohol and IL-6 Alter Expression of Synaptic Proteins in Cerebellum of Transgenic Mice with Increased Astrocyte Expression of IL-6

Abstract

Recent studies indicate that neuroimmune factors, including the cytokine interleukin-6 (IL-6), play a role in the CNS actions of alcohol. The cerebellum is a sensitive target of alcohol, but few studies have examined a potential role for neuroimmune factors in the actions of alcohol on this brain region. A number of studies have shown that synaptic transmission, and in particular inhibitory synaptic transmission, is an important cerebellar target of alcohol. IL-6 also alters synaptic transmission, although it is unknown if IL-6 targets are also targets of alcohol. This is an important issue because alcohol induces glial production of IL-6, which could then covertly influence the actions of alcohol. The persistent cerebellar effects of both IL-6 and alcohol typically involve chronic exposure and, presumably, altered gene and protein expression. Thus, in the current studies we tested the possibility that proteins involved in inhibitory and excitatory synaptic transmission in the cerebellum are common targets of alcohol and IL-6. We used transgenic mice that express elevated levels of astrocyte produced IL-6 to model persistently elevated expression of IL-6, as would occur in alcohol use disorders, and a chronic intermittent alcohol exposure/withdrawal paradigm (CIE/withdrawal) that is known to produce alcohol dependence. Multiple cerebellar synaptic proteins were assessed by Western blot. Results show that IL-6 and CIE/withdrawal have both unique and common actions that affect synaptic protein expression. These common targets could provide sites for IL-6/alcohol exposure/withdrawal interactions and play an important role in cerebellar symptoms of alcohol use such as ataxia.

Keywords: GABA(A) receptor subunits; cytokine; glia; glutamate receptor subunits; neuroimmune; vesicular transporters.