AMPK-SIRT1 pathway dysfunction contributes to neuron apoptosis and cognitive impairment induced by sevoflurane

Abstract

The anesthetic sevoflurane (Sev) is widely used because of its low blood-gas partition coefficient and lack of pungency. However, the application of Sevmay lead to cogni- tive impairment later in life. Previous results have indicated that exposure to Sev-induced neuronal apoptosis and cogni- tive dysfunction in a rat model, but much work remains to elucidate the mechanism. In the present study, inhibition in the AMP-activated protein kinase/Sirtuin 1 (AMPK/SIRT1) signaling pathway and a decrease in AMPK/SIRT1 activity was found to occur concomitantly in neuronal apoptosis induced by Sev. AICAR, an activator of AMPK, was able to suppress Sev-induced neuronal apoptosis and SIRT1 activity reduction in vitro. Further animal studies also showed that AICAR treat- ment blocked the deleterious cognition and AMPK/SIRT1 activity reduction in the cognition impairment rats induced by Sev. Taken together, it was concluded that the AMPK/SIRT1 signaling pathway mediates neuronal apoptosis and cognition impairment induced by Sev. The study provides evidence that AMPK activation ameliorates Sev-induced cognitive deficits.