Coenzyme Q10 reduces sevoflurane-induced cognitive deficiency in young mice

Abstract

BackgroundAnaesthesia can induce cognitive deficiency in young rodents and monkeys. Mitochondrial dysfunction contributes to the anaesthesia-induced neurotoxicity and neurobehavioural deficits. We therefore assessed the effects of the mitochondrial energy enhancer coenzyme Q10 (CoQ10) on anaesthesia-induced cognitive deficiency in young mice to investigate the role of mitochondrial dysfunction. MethodsYoung mice (n=134) were randomly assigned into the following four groups: control plus corn oil vehicle (60% oxygen); 3% sevoflurane [2 h daily on postnatal day (P) 6, 7, and 8] plus vehicle; CoQ10 (50 mg kg−1) plus vehicle; or 3% sevoflurane plus CoQ10 plus vehicle. We determined cognitive function using the Morris water maze at P31-P37. We quantified brain postsynaptic density protein-95, the presynaptic marker synaptophysin, adenosine triphosphate, reactive oxygen species, and mitochondrial membrane potential at P8 and P37. ResultsCoenzyme Q10 reduced sevoflurane-induced cognitive deficiency in young mice (F=0.90, P=0.49, n=10–16) and attenuated sevoflurane-induced reductions in postsynaptic density protein-95 (F=10.56, P<0.01, n=6), synaptophysin (F=8.44, P=0.01, n=6), adenosine triphosphate (F=4.34, P=0.05, n=9), and mitochondrial membrane potential (F=11.43, P<0.01, n=6), but not sevoflurane-induced increases in reactive oxygen species (F=1.17, P=0.20, n=6), in brain. ConclusionsThese data suggest that CoQ10 reduces sevoflurane-induced cognitive deficiency by mitigating sevoflurane-induced mitochondrial dysfunction, the reduction in adenosine triphosphate, and synaptic dysfunction. Coenzyme Q10 could provide an approach to reduce the neurotoxicity of anaesthesia in the developing brain.