Regulatory Effects of Different Concentrations of Sevoflurane on Transcriptomic Changes in a Rotenone-Induced Drosophila Parkinson’s Disease Model

ABSTRACT

Objective: This study aimed to investigate the transcriptomic regulatory effects of different concentrations of sevoflurane on a rotenone (ROT)-induced Drosophila model of Parkinson’s disease (PD), and to elucidate the neuroprotective potential and underlying molecular mechanisms of sevoflurane. Methods: RNA sequencing was performed on the ROT model group, 1%, 2%, and 3% sevoflurane intervention groups (ROT_SEV1, ROT_SEV2, ROT_SEV3), and a separate 3% sevoflurane-only treatment group (SEV3). The effects of sevoflurane intervention were systematically evaluated using principal component analysis (PCA), differential gene expression analysis (DEGs), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and weighted gene co-expression network analysis (WGCNA). Results: Compared with the ROT group, all sevoflurane intervention groups exhibited distinct separation at the transcriptomic level, with the number of differentially expressed genes increasing in a concentration-dependent manner. The ROT_SEV3 showed significant activation of pathways related to antioxidative defense, metabolic homeostasis, and immune regulation, effectively reversing the transcriptomic abnormalities induced by ROT. WGCNA identified co-expression modules highly associated with the ROT condition, which were markedly downregulated following sevoflurane intervention. Minimal differences were observed between the ROT_SEV1 and ROT_SEV2 groups, while ROT_SEV3 exhibited pronounced transcriptomic changes, suggesting a dose- dependent regulatory effect. Conclusion: Sevoflurane effectively alleviates transcriptomic abnormalities in the ROT-induced Drosophila PD model, with the strongest intervention effects observed at a 3% concentration. Its protective mechanisms may involve antioxidative defense, energy metabolism regulation, and immune homeostasis, providing a theoretical basis for the application of sevoflurane in neurodegenerative disease interventions. PD is a common neurodegenerative disorder