Abstract
Chemotherapy-induced cognitive impairment (CICI) is widely recognized as a frequent adverse side effect following the administration of chemotherapeutic agents. This study aimed to explore the neuroprotective functions and mechanisms of microRNAs (miRNAs) mediated by dexmedetomidine (Dex) on cisplatin-induced CICI. The model rats received 5 mg/kg cisplatin injections once per week for 4 weeks. Dex (30 μg/kg) was administered before cisplatin treatment. The protective effects of Dex were evaluated using Morris water maze, Nissl staining, and transmission electron microscopy. Dex-mediated miRNAs were screened via miRNA sequencing. The effects of Dex and key miRNAs on mitochondrial DNA gene mt-ND1 and caspase-9 expression were tested. Dex exhibited a protective effect against decreased learning memory ability, hippocampal neuronal damage, and mitochondrial damage in CICI rats. Thirty-nine differentially expressed (DE) miRNAs were screened, 13 of which responded positively to Dex treatment. Gene Ontology annotation identified that DE miRNAs were mainly involved in transcription, DNA-templated. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DE miRNAs were mainly involved in neuronal function and brain development-related pathways, such as axon guidance and calcium signaling pathways. Compared to cisplatin treatment, the expression of miR-429-3p responded more strongly to Dex treatment. In cisplatin-treated cultured hippocampal neurons, Dex treatment and miR-429-3p overexpression significantly increased mitochondrial DNA gene mt-ND1expression and decreased caspase-9 expression. Our study suggests that Dex alleviates CICI by modulating miR-429-3p expression in rats. Thus, Dex may be effective in preventing the side effects of cisplatin.