Δευτέρα 8 Μαΐου 2017

Coenzyme Q 10 reduces sevoflurane-induced cognitive deficiency in young mice

<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Anaesthesia 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 Q<sub>10</sub> (CoQ<sub>10</sub>) on anaesthesia-induced cognitive deficiency in young mice to investigate the role of mitochondrial dysfunction.<strong>Methods.</strong> Young mice (<span style="font-style:italic;">n</span>=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; CoQ<sub>10</sub> (50 mg kg<sup>−1</sup>) plus vehicle; or 3% sevoflurane plus CoQ<sub>10</sub> 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.<strong>Results.</strong> Coenzyme Q<sub>10</sub> reduced sevoflurane-induced cognitive deficiency in young mice (<span style="font-style:italic;">F</span>=0.90, <span style="font-style:italic;">P</span>=0.49, <span style="font-style:italic;">n</span>=10–16) and attenuated sevoflurane-induced reductions in postsynaptic density protein-95 (<span style="font-style:italic;">F</span>=10.56, <span style="font-style:italic;">P</span><0.01, <span style="font-style:italic;">n</span>=6), synaptophysin (<span style="font-style:italic;">F</span>=8.44, <span style="font-style:italic;">P</span>=0.01, <span style="font-style:italic;">n</span>=6), adenosine triphosphate (<span style="font-style:italic;">F</span>=4.34, <span style="font-style:italic;">P</span>=0.05, <span style="font-style:italic;">n</span>=9), and mitochondrial membrane potential (<span style="font-style:italic;">F</span>=11.43, <span style="font-style:italic;">P</span><0.01, <span style="font-style:italic;">n</span>=6), but not sevoflurane-induced increases in reactive oxygen species (<span style="font-style:italic;">F</span>=1.17, <span style="font-style:italic;">P</span>=0.20, <span style="font-style:italic;">n</span>=6), in brain.<strong>Conclusions.</strong> These data suggest that CoQ<sub>10</sub> reduces sevoflurane-induced cognitive deficiency by mitigating sevoflurane-induced mitochondrial dysfunction, the reduction in adenosine triphosphate, and synaptic dysfunction. Coenzyme Q<sub>10</sub> could provide an approach to reduce the neurotoxicity of anaesthesia in the developing brain.</span>

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