G Xu1,2, H Lu2,3, Y Dong2, D Shapoval2, S G Soriano4, X Liu1, Y Zhang2, Z Xie2. 1. Department of Anesthesiology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022, People's Republic of China. 2. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. 3. Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, People's Republic of China. 4. Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: 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 10 (CoQ 10 ) on anaesthesia-induced cognitive deficiency in young mice to investigate the role of mitochondrial dysfunction. METHODS: Young 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; CoQ 10 (50 mg kg -1 ) plus vehicle; or 3% sevoflurane plus CoQ 10 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. RESULTS: Coenzyme Q 10 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. CONCLUSIONS: These data suggest that CoQ 10 reduces sevoflurane-induced cognitive deficiency by mitigating sevoflurane-induced mitochondrial dysfunction, the reduction in adenosine triphosphate, and synaptic dysfunction. Coenzyme Q 10 could provide an approach to reduce the neurotoxicity of anaesthesia in the developing brain.
BACKGROUND: 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 10 (CoQ 10 ) on anaesthesia-induced cognitive deficiency in young mice to investigate the role of mitochondrial dysfunction. METHODS: Young 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; CoQ 10 (50 mg kg -1 ) plus vehicle; or 3% sevoflurane plus CoQ 10 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. RESULTS: Coenzyme Q 10 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. CONCLUSIONS: These data suggest that CoQ 10 reduces sevoflurane-induced cognitive deficiency by mitigating sevoflurane-induced mitochondrial dysfunction, the reduction in adenosine triphosphate, and synaptic dysfunction. Coenzyme Q 10 could provide an approach to reduce the neurotoxicity of anaesthesia in the developing brain.
Authors: Marwa M Nagib; Mariane G Tadros; Rania M Rahmo; Nagwa Ali Sabri; Amani E Khalifa; Somaia I Masoud Journal: Neurotox Res Date: 2018-10-29 Impact factor: 3.911