Chronic Ethanol Exposure Alters the Expression of Genes Associated with GPCR-Related Signaling in the Olfactory Bulb of Male Mice

07/09/2026

AI Summary

Chronic intermittent ethanol exposure altered olfactory bulb transcriptome in male mice, yielding 188 differentially expressed genes (68 upregulated, 120 downregulated).
Pathway analyses showed predominant enrichment for receptor-mediated signalling, especially G protein-coupled receptor pathways, with eight core GPCR-related genes highlighted.
qRT-PCR validated marked downregulation of Cxcl10, Grp, Pcp2 and Pdyn, suggesting selective impairment of GPCR related signalling and olfactory dysfunction.

AI Summary

Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway database (Reactome) analyses indicated that ethanol-responsive genes were predominantly enriched in receptor-mediated signaling pathways, particularly those linked to G protein-coupled receptor (GPCR) signaling.

Protein-protein interaction analysis further identified eight core GPCR-related genes. quantitative real-time PCR (qRT-PCR) validation revealed that Cxcl10, Grp, Pcp2, and Pdyn were markedly downregulated in the ethanol group.

These results suggest that chronic ethanol exposure is associated with transcriptional alterations in the male mouse olfactory bulb and may selectively affect several GPCR-related signaling components.

Basic summary

Alcohol. 2026 Sep 5:S0741-8329(26)00235-1. doi: 10.1016/j.alcohol.2026.09.003. Online ahead of print.

ABSTRACT

Chronic ethanol exposure, a key feature of alcohol use disorder (AUD), can affect the nervous system, but its molecular impact on the olfactory bulb remains unclear. In this study, an intermittent two-bottle voluntary drinking model was established in male mice, and transcriptome sequencing was performed on olfactory bulb tissues. DESeq2 analysis identified 188 differentially expressed genes, including 68 upregulated and 120 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway database (Reactome) analyses indicated that ethanol-responsive genes were predominantly enriched in receptor-mediated signaling pathways, particularly those linked to G protein-coupled receptor (GPCR) signaling. Protein-protein interaction analysis further identified eight core GPCR-related genes. quantitative real-time PCR (qRT-PCR) validation revealed that Cxcl10, Grp, Pcp2, and Pdyn were markedly downregulated in the ethanol group. These results suggest that chronic ethanol exposure is associated with transcriptional alterations in the male mouse olfactory bulb and may selectively affect several GPCR-related signaling components. This study provides candidate molecular evidence for further investigation of ethanol-associated olfactory dysfunction.

PMID:42700876 | DOI:10.1016/j.alcohol.2026.09.003

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