Dexmedetomidine attenuates surgery-induced cognitive deficit and hippocampal Mapt expression in aged mice

Background Postoperative cognitive dysfunction is a significant complication, but the mechanisms underlying this condition and its impact on the brain network are not fully elucidated. The goals of this study were to verify how the transcriptional network in the hippocampus of aged mice changes following sevoflurane/surgery-induced stress and to substantiate how dexmedetomidine influences the cognitive function and mRNA changes in the hippocampus.Materials and methods We first performed transcriptome analysis to confirm the changes of mRNA expression in the Naïve and Ope (surgery under sevoflurane) groups. Then, the mice were divided into four groups: Naïve, Sevo (sevoflurane exposure), Ope, and Dex (dexmedetomidine injection before surgery). We selected the Mapt gene, the upregulated expression of which has been observed in our transcriptome analysis and in neurodegenerative disorders, as the target gene and investigated whether the changes in its expression occurred in the hippocampus using quantitative rev transcription polymerase chain reaction (qRT-PCR). The cognitive function of mice was evaluated via the Barnes Maze test.Results In the qRT-PCR analysis, Mapt expression was significantly upregulated (2.60 ± 0.77 in mice from the Ope group vs. 1.00 ± 0.11 in mice from the Naïve group [mean ± SD for fold change]; p<0.01). Dexmedetomidine significantly attenuated the sevoflurane/surgery-induced upregulation of Mapt expression in the hippocampus (0.88 ± 0.32; p<0.01). Sevoflurane/surgery-induced stress also increased the time to identify the target box, and dexmedetomidine treatment inhibited the time extension 7, 14, and 28 days after the surgery.Conclusions Dexmedetomidine attenuates the sevoflurane/surgery-induced cognitive deficit and Mapt expression in the hippocampus of aged mice.