Ethanol-Induced Behavioral Sensitization Alters the Synaptic Transcriptome and Exon Utilization in DBA/2J Mice

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Alcoholism involves compulsive ethanol consumption and loss of control.
• Ethanol-induced behavioral changes are linked to altered gene expression affecting synaptic plasticity.
• Localized mRNA translation at synapses is crucial for synaptic plasticity, but its role in ethanol's effects is unknown.

Purpose of the Study:

• To investigate if repeated ethanol exposure alters the synaptic transcriptome.
• To understand the contribution of synaptic transcriptome changes to ethanol-induced neuroplasticity and behavioral sensitization.

Main Methods:

• Utilized RNA sequencing (RNAseq) on frontal pole synaptoneurosomes from DBA/2J mice.
• Compared gene expression profiles after acute ethanol exposure versus ethanol-induced behavioral sensitization.
• Analyzed differential exon usage and enriched gene targets.

Main Results:

• Ethanol sensitization significantly altered more synaptic genes than acute exposure.
• Synaptic processes affected included protein folding, modification, and mitochondrial respiration.
• Differential exon usage, particularly in RNA processing and synaptic function genes, was observed after sensitization.

Conclusions:

• Repeated ethanol exposure modifies the synaptic transcriptome, impacting energy production and protein processing.
• Altered exon usage suggests ethanol sensitization affects mRNA trafficking and stability mechanisms.
• This provides a basis for understanding ethanol's role in synaptic plasticity and addiction.