Protective effects of dexmedetomidine against propofol-induced memory impairment in developing rat involved Src and RARα.

Abstract

BackgroundDexmedetomidine (DEX) can offer protection to the nervous, urinary and circulatory systems. It can alleviate local oxidative stress, reduce inflammatory responses, inhibite cellular autophagy and decrease apoptosis.AimTo explore the potential protection and possible mechanisms of DEX against propofol (PPF)-induced memory impairment in developing rats.Material and methodsThe effects of DEX on spatial learning and passive avoidance abilities of rats were evaluated using eight-arm mirror maze and passive avoidance experiments. mRNA levels were detected using RT-qPCR analysis while protein levels were determined using western blot. A network pharmacology approach was used to predict potential targets of DEX against PPF-induced memory impairment. The cell autophagy and apoptosis were detected using commercial kits.ResultsDEX improved the impairment of developing rats on spatial learning and passive avoidance caused by PPF exposure. DEX regulates autophagic activity to inhibit neuronal apoptosis. RARα and Src were potential targets for DEX against memory impairment caused by PPF exposure. DEX upregulated the expression levels of Bdnf, p-CREB/CREB, p-Akt/Akt, and p-TrkB/TrkB proteins.ConclusionDEX may regulate Bdnf/TrkB and activate the activity of the PI3K/Akt signaling pathway by targeting RARα and Src, thereby inhibiting excessive autophagy and alleviating memory impairment.