Transcriptome Analysis of Hippocampus After Weekly Binge Alcohol Exposure and Voluntary Exercise in Rats

Methods

Male and female rats were gavaged once weekly for 5 weeks with 5 g/kg ethanol or isocaloric control solution. Half of the animals had access to running wheels 4 d/wk. All animals were euthanized immediately following the final exercise session/~18-20 hours after the last binge exposure.

The hippocampus was microdissected and RNA extracted and sequenced.Results: Transcription of 806 genes was altered by exercise, but only 7 by binge alcohol, most of which were transcription factors. Only 1 gene, Zfp62, showed evidence for an interaction effect. Direct comparisons within exercised groups showed that exercise altered gene expression only in control (not binge) animals.

Gene ontology (GO) analysis identified pathways associated with receptor signaling, namely protein kinase signaling, as differentially impacted by exercise. Deconvolution methods were used to explore gene expression changes in specific cell populations. This analysis indicated that expression differences found in bulk RNA-Seq were not cell-type specific.

Conclusions: Our results suggest that binge alcohol does not exert numerous effects on next-day gene expression. However, it likely delays exercise effects on the transcriptome, suggesting future study of this interaction is merited. Deconvolution showed similar patterns, upholding its utility as a supplemental analysis for bulk sequencing studies.