Exploring the mechanisms of hippocampal neurotoxicity induced by cypermethrin: Insights from integrated miRNA-seq and mRNA-seq analysis

Cypermethrin (CMN) is a synthetic pyrethroid insecticide known for its neurotoxic effects, particularly in the hippocampus. To investigate the underlying molecular mechanisms, we conducted integrated microRNA (miRNA) and messenger RNA (mRNA) sequencing in HT22 hippocampal cells treated with 400 μM CMN. We identified 36 differentially expressed miRNAs and 170 target mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed significant involvement in cell adhesion, extracellular matrix organization, and signaling pathways such as phosphoinositide 3-kinase–protein kinase B signaling pathway (PI3K-Akt), mitogen-activated protein kinase (MAPK), and extracellular matrix (ECM)–receptor interaction. Using six topological algorithms, three hub genes (Col1a2, Fn1, and Pdgfrb) were finally identified. In addition, a miRNA–mRNA regulatory network was constructed, and expression patterns of key miRNAs and mRNAs were validated via reverse transcription polymerase chain reaction (RT-PCR). These findings highlight the critical role of the miRNA–mRNA regulatory network in CMN-induced neurotoxicity. The study provides valuable insights into potential therapeutic targets and preventive strategies for CMN-associated hippocampal damage.