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

Children with multiple exposures to anesthesia and surgery may be more likely to develop 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 4 groups: Control + corn oil, Sevoflurane + corn oil, Control + CoQ10 and Sevoflurane + CoQ10. Sevoflurane group mice were anesthetized with 3% sevoflurane and 60% oxygen 2 hours a day for 3 days, while control group mice received only 60% oxygen. Mice received intraperitoneal injection of 50mg/kg CoQ10 or the same volume of corn oil 30 min before inhalation of oxygen or sevoflurane for 3 days. 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 reversed 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.