Cerebellar Transcriptomic Analysis in a Chronic plus Binge Mouse Model of Alcohol Use Disorder Demonstrates Ethanol-Induced Neuroinflammation and Altered Glial Gene Expression

Cerebellar Transcriptomic Analysis in a Chronic plus Binge Mouse Model of Alcohol Use Disorder Demonstrates Ethanol-Induced Neuroinflammation and Altered Glial Gene Expression

Alcohol use disorder (AUD) is 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 regu...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2023-02, Vol.12 (5), p.745
Main Authors: Holloway, Kalee N, Pinson, Marisa R, Douglas, James C, Rafferty, Tonya M, Kane, Cynthia J M, Miranda, Rajesh C, Drew, Paul D
Format: Article
Language:eng
Subjects:
Alcoholism
Alcoholism - pathology
Animals
astrocyte
AUD
Cerebellum
Cerebellum - metabolism
Chronic Disease
Ethanol - metabolism
Gene expression
Genetic aspects
Health aspects
Inflammation
Mice
Mice, Inbred C57BL
microglia
Neuroglia
neuroinflammation
Neuroinflammatory Diseases
oligodendrocyte
RNA
RNA - metabolism
Transcriptome
transcriptomics
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Summary:Alcohol use disorder (AUD) is 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, and RNA was isolated and submitted for RNA-sequencing. 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 homeostasis-associated transcripts and an increase in transcripts associated with chronic neurodegenerative diseases, while astrocyte-associated genes showed an increase in transcripts associated with acute injury. Oligodendrocyte lineage cell genes showed a decrease in transcripts associated with both immature progenitors as well as myelinating oligodendrocytes. These data provide new insight into the mechanisms by which ethanol induces cerebellar neuropathology and alterations to the immune response in AUD.
ISSN:2073-4409
2073-4409