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Exploring the mechanisms of hippocampal neurotoxicity induced by cypermethrin: Insights from integrated miRNA-seq and
Jingran Yang1, Ruirui Ding1, Ling Qi1
1Department of Occupational and Environmental Health, College of Public Health, Xuzhou Medical University, 209 Tongshan Road, Yun Long District, Xuzhou 221000, China.
Abstract:
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.
Insights
Cypermethrin insecticide damages the hippocampus by altering microRNA and messenger RNA. This study reveals a key regulatory network, offering insights into potential treatments for neurotoxicity.
Area of Science:
- Neuroscience
- Molecular Biology
- Toxicology
Background:
- Cypermethrin (CMN), a synthetic pyrethroid, exhibits neurotoxic effects, particularly impacting the hippocampus.
- Understanding the molecular basis of CMN-induced hippocampal damage is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the molecular mechanisms of cypermethrin neurotoxicity using integrated microRNA (miRNA) and messenger RNA (mRNA) sequencing.
- To identify key regulatory networks and potential therapeutic targets involved in CMN-induced hippocampal damage.
Main Methods:
- Integrated miRNA and mRNA sequencing in HT22 hippocampal cells treated with cypermethrin (400 μM).
- Bioinformatic analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and topological analysis.
- Validation of key miRNA and mRNA expression using reverse transcription polymerase chain reaction (RT-PCR).
Main Results:
- Identified 36 differentially expressed miRNAs and 170 target mRNAs.
- Enrichment analyses indicated involvement in cell adhesion, extracellular matrix organization, and signaling pathways (PI3K-Akt, MAPK, ECM-receptor interaction).
- Identified three hub genes (Col1a2, Fn1, Pdgfrb) and constructed a miRNA-mRNA regulatory network.
Conclusions:
- The miRNA-mRNA regulatory network plays a critical role in cypermethrin-induced neurotoxicity.
- Findings provide valuable insights into potential therapeutic targets and preventive strategies for cypermethrin-associated hippocampal damage.
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