Sevoflurane induces cognitive impairment in young mice via autophagy

• Published in: PloS one Vol. 14; no. 5; p. e0216372
• Main Authors: Wang, Xiaoning, Dong, Yuanlin, Zhang, Yiying, Li, Tianzuo, Xie, Zhongcong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20-05-2019; Public Library of Science (PLoS)
• Subjects: Activation; Anesthesia; Anesthesia, Inhalation - adverse effects; Anesthesiology; Anesthetic gases; Animal cognition; Animals; Apoptosis; Autophagic Cell Death - drug effects; Autophagy; Biology and Life Sciences; Brain; Brain research; Cell death; Central nervous system agents; Cognition; Cognitive ability; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; Cognitive Dysfunction - physiopathology; Complications and side effects; Critical care; Dosage and administration; Gender differences; Hippocampus; Hippocampus - metabolism; Hippocampus - pathology; Hippocampus - physiopathology; Hospitals; Impairment; Laboratory rats; Maze Learning - drug effects; Medical research; Medical schools; Medicine; Medicine and Health Sciences; Mice; Microtubule-Associated Proteins - metabolism; Nervous system diseases; Neurodegenerative diseases; Neurological diseases; Neurotoxicity; Neurotoxicity syndromes; Pain; Phagocytosis; Physical Sciences; Proteins; Research and Analysis Methods; Risk factors; Rodents; Sequestosome-1 Protein - metabolism; Sevoflurane; Sevoflurane - adverse effects; Sevoflurane - pharmacology; Studies; Western blotting; United States; Beijing China; United States > US; Massachusetts; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0216372

Anesthesia 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.
Six 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.
The 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.
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. 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.