Protective effects of Coenzyme Q10 against sevoflurane-induced cognitive impairment through regulating apolipoprotein E and phosphorylated Tau expression in young mice
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Published on: January 22, 2017
Insights
Coenzyme Q10 (CoQ10) reversed sevoflurane anesthesia-induced cognitive deficits in young mice. This protection involves reducing ApoE expression and improving energy and mitochondrial function, highlighting CoQ10
Area of Science:
- Neuroscience
- Anesthesiology
- Biochemistry
Background:
- Repeated anesthesia exposure in children may increase learning disability risk.
- Coenzyme Q10 (CoQ10) has shown potential in mitigating anesthesia-induced cognitive issues in young mice.
- The precise mechanisms underlying CoQ10's protective effects against sevoflurane-induced cognitive deficiency remain unclear.
Purpose of the Study:
- To investigate the role of Apolipoprotein E (ApoE) in sevoflurane anesthesia-induced cognitive deficiency.
- To elucidate the protective mechanisms of CoQ10 in a mouse model of multiple sevoflurane exposures.
- To determine if CoQ10 can prevent anesthesia-related cognitive impairment in early life.
Main Methods:
- Young mice (postnatal days 6-8) were exposed to sevoflurane anesthesia or control conditions for 3 days.
- Mice received daily intraperitoneal injections of CoQ10 (50 mg/kg) or corn oil prior to anesthesia/control exposure.
- Cognitive function was assessed using the Morris water maze (P30-P36). Brain tissues (cortex, hippocampus) were analyzed for ATP, mitochondrial membrane potential (MMP), ApoE, amyloid-beta (Aβ), and tau phosphorylation markers.
Main Results:
- Sevoflurane anesthesia led to energy deficiency, mitochondrial dysfunction, increased ApoE and its fragments, elevated Aβ1-42, and tau phosphorylation.
- CoQ10 administration reversed these anesthesia-induced changes, including improved ATP levels and MMP.
- CoQ10 treatment significantly ameliorated cognitive impairment observed in the Morris water maze tests.
Conclusions:
- ApoE and its fragments play a significant role in the pathogenesis of sevoflurane-induced cognitive deficiency.
- CoQ10 exerts neuroprotective effects by enhancing energy replenishment and mitochondrial function.
- CoQ10 alleviates sevoflurane-induced brain damage and cognitive impairment, suggesting a therapeutic potential for anesthesia-related neurotoxicity.
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 2 hr a day for 3 days, while control group mice received only 60% oxygen. Mice received an intraperitoneal injection of 50 mg/kg CoQ10 or the same volume of corn oil 30 min before the 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 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.

