Chronic Intermittent Ethanol Exposure Alters Synaptic Protein Expression in the Mouse Lateral Orbitofrontal Cortex
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Moss, Julia Lois
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Abstract
Alcohol use disorders (AUDs) are chronic, relapsing conditions characterized by excessive alcohol consumption and various behavioral deficits. Changes to brain regions, including the orbitofrontal cortex (OFC), a region involved in reversal learning tasks and the regulation of impulsive behaviors, have been linked to the functional impairments that follow chronic alcohol use in both humans and rodent models. A recent study from our lab demonstrated an increase in the density of long, thin dendritic spines of basal dendrites in the lateral OFC (lOFC) layer II/III pyramidal neurons following withdrawal from chronic intermittent ethanol (CIE) treatment. We hypothesized changes in synaptic protein expression would accompany this alteration and performed a proteomics analysis to compare expression in the post-synaptic density of neurons in the lOFC of CIE-treated mice versus unexposed controls. CIE exposure significantly altered 29 proteins, many of which are involved in glutamatergic signaling and regulation of dendritic spine morphology. Western blot analysis confirmed significant changes in the expression of some of these proteins – growth associated protein-43 (GAP-43), elongation factor 1 (EF1-α1), synaptopodin, α actinin, and excitatory amino acid transporter-2 (EAAT2). Protein-level changes, such as those demonstrated in the present study, likely affect dendritic spine morphology and glutamatergic signaling, as many of these proteins are known to play a role in these processes. The OFC-dependent functional and behavioral deficits associated with chronic alcohol use likely are related to singular or combined effects of these physiological changes – altered protein expression, dendritic spine remodeling, and abnormal glutamatergic signaling – at the tripartite synapse.
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OFC, alcohol, alcohol use disorder, proteomics, iTRAQ, CIE