Protective effects of Coenzyme Q10 against sevoflurane-induced cognitive impairment through regulating apolipoprotein E and phosphorylated Tau expression in young mice.

Abstract

Children with multiple exposures to anesthesia and surgery may be more likely to develop the learning disability. Coenzyme Q10 (CoQ10) was reported to reduce the multiple sevoflurane treatment-induced cognitive deficiency in 6-day-old young mice. However, its specific mechanisms have not yet been found. This research aimed to reveal the role of ApoE in the pathogenesis of cognitive deficiency caused by sevoflurane anesthesia and the protective mechanism of CoQ10 in a multiple sevoflurane treatment model of young mice. The mice were randomly divided into four groups: Control+corn oil, Sevoflurane+corn oil, Control+CoQ10, and Sevoflurane+CoQ10. Sevoflurane group mice were anesthetized with 3% sevoflurane and 60% oxygen 2hr a day for 3days, while control group mice received only 60% oxygen. Mice received an intraperitoneal injection of 50mg/kg CoQ10 or the same volume of corn oil 30min before the inhalation of oxygen or sevoflurane for 3days. Mice received sevoflurane anesthesia or control treatment from the 6th to 8th day after birth. The cortex and hippocampus were harvested on the 8th day. The ATP, MMP, ApoE mRNA, total ApoE, ApoE fragments, Aβ1-40, Aβ1-42, Tau5, AT8, and PHF levels were detected. The Morris water maze (MWM) tests were performed from P30 to p36 after anesthesia or control treatment. The results indicated that the injection of CoQ10 ahead of sevoflurane treatment could reverse the anesthesia-induced energy deficiency, mitochondrial dysfunction, ApoE, and its fragments expression, Aβ1-42 generation, Tau phosphorylation, and cognitive impairment in young mice. These data reveal that the ApoE and its fragments enhancement may play an important role in the pathogenesis of cognitive deficiency caused by sevoflurane anesthesia. CoQ10 could reduce ApoE expression by improving energy replenishment and mitochondrial functions, thereby alleviating sevoflurane-induced brain damage and cognitive impairment.