AMPK-SIRT1-PGC1 α Signal Pathway Influences the Cognitive Function of Aged Rats in Sevoflurane-Induced Anesthesia

AbstractTo understand the effect of AMP-activated protein kinase (AMPK)-SIRT1 (silent information regulator 1)-PPAR γ coactivator-1α (PGC1α) signaling pathway on the cognitive function of sevoflurane-anesthetized aged rats. Aged rats were divided into Normal group, Sevo group (Sevoflurane anesthesia), Sevo + AICAR (the AMPK activator) group, Sevo + EX527 group (the AMPK inhibitor), and Sevo + AICAR + EX527 gro up. The cognitive function of rats was determined by the Morris water maze. Hippocampal neuronal apoptosis was evaluated by TUNEL and Fluoro-Jade C (FJC) staining, and the expression of cleaved caspase-3 was detected by immunohistochemistry. ROS, SOD, and MDA levels and the fluorescence intensity of GFAP in the hippocampus were assayed. The mitochondrial membrane potential (MMP), mitochondrial mass, ATP level, and the expression of AMPK-SIRT1-PGC1α were determined by the corresponding methods. Rats in the Sevo group manifested significant extension in the escape latency, with fewer platform c rossings; and meanwhile, the apoptotic rate, the number of FJC-positive cells, and the fluorescence intensity of GFAP of neurons were elevated, with up-regulation of cleaved caspase-3. Moreover, the level of MDA and ROS was increased evidently, with significant down-regulation of SOD activity, ATP, mitochondrial mass and MMP levels, and AMPK, SIRT1 and PGC-1α protein expressions. However, sevoflurane-induced changes above were improved after the administration of AICAR, and EX...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research