Synaptic microRNAs Coordinately Regulate Synaptic mRNAs: Perturbation by Chronic Alcohol Consumption.

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Local mRNA translation in synapses is crucial for neuronal function.
• Chronic alcohol consumption alters synaptic mRNA expression, potentially via microRNAs.
• Synaptoneurosomes (SN) offer a model for studying synaptic transcriptomes.

Purpose of the Study:

• To identify microRNAs targeting alcohol-induced mRNAs within synaptoneurosomes.
• To define alcohol-responsive synaptic microRNAs and their interactions with mRNAs.
• To elucidate how alcohol perturbs microRNA-mRNA regulatory networks at the synapse.

Main Methods:

• Profiling of microRNAs and mRNAs in synaptoneurosomes from alcohol-exposed mice.
• Utilizing bioinformatic analyses: differential expression, correlation, co-expression, and target prediction.
• Comparing alcohol effects in synaptoneurosomes versus total brain homogenates.
• Performing cell type-specific analyses to pinpoint neuronal targets.

Main Results:

• Identified alcohol-responsive microRNAs and mRNAs with correlated expression patterns.
• Discovered a subset of microRNAs predicted to target numerous alcohol-responsive mRNAs.
• Revealed cell type-specific alterations, with many alcohol-responsive elements unique to glutamate neurons.
• Found evidence of predicted microRNA-mRNA interactions within glutamate neurons.

Conclusions:

• Chronic alcohol consumption disrupts coordinated microRNA regulation of mRNAs in synaptoneurosomes.
• Altered synaptic microRNA-mRNA interactions may underlie synaptic plasticity deficits in alcoholism.
• These findings highlight a novel mechanism contributing to the neurobiological effects of alcohol.