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

Binge alcohol exposure is associated with neurodegeneration in corticolimbic regions in both humans and animal models. We have previously shown that exercise limits hippocampal damage and neuroimmune activation in rats. Here we conducted a transcriptome analysis in order to elucidate genetic mechanisms underlying the protective influence of exercise on the binged hippocampus.

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 days/week. All animals were euthanized immediately following the final exercise session/c. 18-20 h after the last binge exposure. The hippocampus was microdissected and RNA extracted and sequenced.

Transcription of 806 genes was altered by exercise, but only seven by binge alcohol, most of which were transcription factors. Only one 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.

Our results suggest that five weekly treatments of binge alcohol minimally alter the hippocampal transcriptome assessed 20 h after the last binge. However, binge ethanol exposure markedly blunted 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.