Identification of core genes and molecular prediction of drug targets for countering BPA-induced olfactory bulb neurotoxicity in male mice.

Bisphenol A (BPA) is ubiquitous in plastics, which can modify and improve the applicability and durability of plastics. Previous laboratory studies have shown that BPA can trigger cognitive impairment and depression. The olfactory bulb (OB) is significantly related to cognition and depression. However, there is a deficiency in information on BPA-induced OB neurotoxicity. Therefore, we analyzed the OB tissues of male mice at the transcriptional level after BPA poisoning at four different levels of concentration (0, 0.01, 0.1, and 1 μg/mL). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and weighted gene co-expression network analysis (WGCNA) were used to screen critical pathways and core genes. The result demonstrated that the PI3K-AKT signaling pathway might play a crucial role in the effects of BPA on the OB. In addition, two genes of the PI3K-AKT signaling pathway, the colony stimulating factor-1 receptor (Csf1r) and the toll-like receptor 2 (Tlr2), were screened by the protein-protein interaction networks. Furthermore, molecular docking identified ceftolozane as a potential drug candidate that could counteract BPA-related OB neurotoxicity. Conclusively, our results confirmed that BPA induced OB damage in male mice through the PI3K-AKT pathway and proposed that ceftolozane might reduce BPA-induced OB neurotoxicity.