Dexmedetomidine attenuates isoflurane-induced neuroapoptosis through the miR-137/GSK-3β pathway in the developing rat hippocampus.

Long-term isoflurane inhalation has been reported to induce hippocampal apoptosis in young animals, whereas dexmedetomidine (DEX) can reduce isoflurane-induced neuronal apoptosis. The neuroprotective effect of miR-137 has been reported before, however, the effect of on isoflurane triggered neuronal apoptosis, and whether miR-137 is involved in the neuroprotection of DEX remain unclear. To investigate these doubts, we established an isoflurane exposure model in postnatal day 7 (P7) Sprague‒Dawley rats and the PC12 cells, containing a control group (CON), isoflurane group (ISO), DEX group (DEX) and DEX pretreatment group (DEX + ISO). We first confirmed that DEX attenuates isoflurane-induced hippocampal apoptosis. And we found DEX increased miR-137 and attenuated GSK-3β levels in the DEX and DEX + ISO groups in the hippocampus and PC12 cells. In addition, the regulative relationship of miR-137 and GSK-3β was confirmed using the TargetScan tool and dual-luciferase reporter assay. Moreover, miR-137 overexpression inhibited GSK-3β and increased its downstream gene β-catenin, whereas knockdown of miR-137 changed the GSK-3β and β-catenin expression oppositely. Upregulation of miR-137 increased the apoptosis-related genes and decreased the anti-apoptosis gene; however, knockdown of miR-137 produced the opposite results. This study suggested that DEX attenuated isoflurane-induced neuroapoptosis by upregulating the miR-137 mediated GSK-3β/β-catenin pathway in the developing rat hippocampus.