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Effects of sevoflurane on the expression of tau protein m RNA and Ser396/404 site in the hippocampus of developing rat brain
Author(s) -
Hu Zhiyong,
Jin Haiyan,
Xu Lili,
Zhu Zhirui,
Jiang Yilei,
Seal Robert
Publication year - 2013
Publication title -
pediatric anesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.704
H-Index - 82
eISSN - 1460-9592
pISSN - 1155-5645
DOI - 10.1111/pan.12263
Subject(s) - sevoflurane , western blot , neurotoxicity , medicine , hyperphosphorylation , hippocampus , tau protein , anesthesia , phosphorylation , microbiology and biotechnology , endocrinology , pathology , toxicity , biochemistry , chemistry , biology , alzheimer's disease , disease , gene
Summary Background General anesthesia induces a transient hyperphosphorylation of tau protein that is associated with neurotoxicity in neonatal rats, but the mechanism remains unknown. The current study sought to investigate the effects of sevoflurane on the levels of tau phosphorylation at phosphor‐Ser396/404 and total tau m RNA in the hippocampus of neonatal rats. Materials and Methods Thirty‐six 7‐day‐old rats were randomly exposed for 6 h to either 3% sevoflurane (S) or air ( NC ) as a placebo. They were sacrificed at 1, 7 and 14 days after the anesthesia, respectively, and thus assigned to S 1d , S 7d , S 14d , NC 1d , NC 7d , and NC 14d groups ( n = 6). Their brain tissues were harvested and then subjected to histopathologic, Western blot and real‐time polymerase chain reaction analysis. Results Microtubule cytoskeletons were arranged in neat parallel rows in rats exposed only to air, whereas the microtubules were arranged in a disorderly and intermittent (nonparallel) fashion in rats exposed to sevoflurane. The levels of tau m RNA in the S 1d and S 7d groups were significantly higher than those in the NC 1d and NC 7d groups. There was no significant difference in the levels of tau m RNA between the S 14d and NC 14d groups. The levels of tau protein at Ser404 in the S 1d , S 7d, and S 14d groups were significantly higher than those in NC 1d , NC 7d, and NC 14d groups. The levels of tau protein at Ser396 in the S 1d , and S 7d groups were significantly higher than those in the NC 1d , and NC 7d groups, while there was no significant difference in the levels of tau protein at Ser396 between the S 14d group and the NC 14d group, respectively. Conclusion In rat hippocampus, sevoflurane was associated with microtubular disarray as well as increased levels of tau m RNA and excessive phosphorylation of tau protein at Ser396 and Ser404. This implicates that sevoflurane may induce neurotoxicity.