Chronic Alcohol Exposure Alters Gene Expression and Neurodegeneration Pathways in the Brain of Adult Mice

Background: Chronic alcohol consumption can alter the structure of the central nervous system and disrupt cognitive function. Alcoholics are more likely to develop neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the role of alcohol in promoting neurotoxicity and neurodegeneration remains unclear. Objective: In this study, we aimed at estimating the effects of chronic binge alcohol exposure on brain transcriptome and behavior changes in a chronic “Drinking in the Dark” (DID) mouse model. Methods: The adult C57BL/6J male mice were exposed to alcohol for 4 weeks. RNA-seq was applied to assess the effects of chronic alcohol exposure on transcriptome in brain. The open field test and novel object recognition test were used to assess the changes of anxiety level, locomotive function, and short-term memory induced by alcohol. RNA-seq analysis revealed that chronic alcohol exposure caused significant change in the brain transcriptome, especially in prefrontal cortex. Results: The gene dysregulation caused by chronic alcohol exposure includes pathways related to mitochondrial energy metabolism (such as oxidative phosphorylation) and multiple neurodegenerative diseases (such as AD and PD). Furthermore, the pathway and network analyses suggest that the genes involved in mitochondrial energy metabolism, ubiquitin-proteasome system, Wnt signaling pathway, and microtubules may attribute to the neurotoxicity and neurodegeneration caused by chronic alcohol consumption. Additionally, locomotive function was also significantly impaired. Conclusion: This work provides gene transcriptional profile data for future research on alcohol-induced neurodegenerative diseases, especially AD and PD.