Alcohol and Increased Astrocyte Expression of Cytokine IL-6 Alter Expression of Cerebellar Synaptic Proteins
- Author(s): Melkonian, Claudia
- Advisor(s): Gruol, Donna
- et al.
Neuroimmune factors, such as the cytokine interleukin-6, have been widely implicated in recent studies focusing on the actions of alcohol in the central nervous system. Few studies however have examined the potential role of neuroimmune factors in the actions of alcohol in the cerebellum, a highly sensitive target of alcohol. Synaptic transmission, specifically inhibitory synaptic transmission, has been shown to be an important cerebellar target of alcohol actions. IL-6 alters synaptic transmission as well, however it is unclear if targets of alcohol actions are also IL-6 targets. Alcohol induces glial cells, including astrocytes to produce IL-6, which can in turn influence the actions of alcohol bringing to light the important issues of potential interactions between alcohol and IL-6. The cerebellar effects of alcohol and IL-6 presumably alter gene and protein expression under chronic exposure. Current studies test whether proteins involved with inhibitory and excitatory synaptic transmission in the cerebellum are targets of both alcohol and IL-6. Transgenic mice with elevated levels of astrocyte produced IL-6 were used as models for elevated expression of IL-6 that would typically be seen in alcohol use disorder. A chronic intermittent ethanol exposure and withdrawal paradigm (CIE/withdrawal) was used to produce alcohol dependence in mice. Levels of different synaptic proteins in the cerebellum were studied by Western blot and results show that CIE/withdrawal and IL-6 have distinct and shared actions that alter cerebellar protein expression. The shared targets could highlight alcohol and IL-6 interactions that significantly contribute to the cerebellar consequences of alcohol use such as ataxia.