Cerebellar Transcriptomic Analysis in a Chronic Plus Binge Mouse Model of Alcohol Use Disorders Demonstrate Ethanol Induced Neuroinflammation and Altered Glial Gene Expression

Alcohol use disorders (AUD) are one of the most common preventable mental health disorders and can result in pathology within the CNS, including the cerebellum. Cerebellar alcohol exposure during adulthood has been associated with disruptions in proper cerebellar function. However, the mechanisms regulating ethanol-induced cerebellar neuropathology are not well understood. High-throughput next generation sequencing was performed to compare control versus ethanol treated adult C57BL/6J mice in a chronic plus binge model of AUD. Mice were euthanized, cerebella were microdissected, RNA was isolated, and RNA-sequencing was performed. Down-stream transcriptomic analyses revealed significant changes in gene expression and global biological pathways in control versus ethanol treated mice that included pathogen-influenced signaling pathways and cellular immune response pathways. Microglial associated genes showed a decrease in homeostatic molecules and an increase in molecules associated with chronic neurodegenerative diseases, while astrocyte associated genes showed an increase in molecules associated with acute injury. Oligodendrocyte lineage cell genes showed a decrease in molecules associated with both early-stage progenitors as well as mature myelinating oligodendrocytes. These data provide new insight into the mechanisms by which ethanol induces cerebellar neuropathology and alterations to the immune response in AUD. Compare gene expression of control vs. ethanol treated adult C57BL/6J mice, in a chronic plus binge model of alcohol use disorder (AUD), using RNAseq data.