Abstract
BackgroundAnesthesia may induce neurotoxicity and neurocognitive impairment in young mice. However, the underlying mechanism remains largely to be determined. Meanwhile, autophagy is involved in brain development and contributes to neurodegenerative diseases. We, therefore, set out to determine the effects of sevoflurane on autophagy in the hippocampus of young mice and on cognitive function in the mice.MethodsSix day-old mice received 3% sevoflurane, for two hours daily, on postnatal days (P) 6, 7 and 8. We then decapitated the mice and harvested the hippocampus of the young mice at P8. The level of LC3, the ratio of LC3-II to LC3-I, and SQSTM1/p62 level associated with the autophagy in the hippocampus of the mice were assessed by using Western blotting. We used different groups of mice for behavioral testing via the Morris Water Maze from P31 to P37.ResultsThe anesthetic sevoflurane increased the level of LC3-II and ratio of LC3-II/LC3-I, decreased the p62 level in the hippocampus of the young mice, and induced cognitive impairment in the mice. 3-Methyladenine, the inhibitor of autophagy, attenuated the activation of autophagy and ameliorated the cognitive impairment induced by sevoflurane in the young mice.ConclusionThese data showed that sevoflurane anesthesia might induce cognitive impairment in the young mice via activation of autophagy in the hippocampus of the young mice. These findings from the proof of concept studies have established a system and suggest the role of autophagy in anesthesia neurotoxicity and cognitive impairment in the young mice, pending further investigation.
Highlights
There are about 6 million children who receive various surgeries under anesthesia every year in the United States of America [1]
The anesthetic sevoflurane increased the level of LC3-II and ratio of LC3-II/LC3 is converted from the soluble form (LC3-I), decreased the p62 level in the hippocampus of the young mice, and induced cognitive impairment in the mice. 3-Methyladenine, the inhibitor of autophagy, attenuated the activation of autophagy and ameliorated the cognitive impairment induced by sevoflurane in the young mice
These data showed that sevoflurane anesthesia might induce cognitive impairment in the young mice via activation of autophagy in the hippocampus of the young mice
Summary
There are about 6 million children who receive various surgeries under anesthesia every year in the United States of America [1]. Sevoflurane has been shown to induce cellular apoptosis [8,9,10,11,12,13], endoplasmic reticulum stress [9, 14,15,16], synaptogenesis impairment [17,18,19,20], mitochondrial dysfunction [18, 20] and neuroinflammation [9, 21] in vitro and in vivo in mice These effects may lead to cognitive impairment in young mice [22]. Set out to determine the effects of sevoflurane on autophagy in the hippocampus of young mice and on cognitive function in the mice
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