中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (17): 1590-1596.doi: 10.3969/j.issn.1673-5374.2013.17.007

• 原著:退行性病与再生 • 上一篇    下一篇

氯胺酮诱导新生鼠海马tau蛋白Ser404位点的异常磷酸化

  

  • 收稿日期:2013-02-01 修回日期:2013-04-10 出版日期:2013-06-15 发布日期:2013-06-15

Ketamine induces tau hyperphosphorylation at serine 404 in the hippocampus of neonatal rats

Haiyan Jin1, Zhiyong Hu1, Mengjie Dong2, Yidong Wu3, Zhirui Zhu1, Lili Xu4   

  1. 1 Department of Anesthesiology, The Children’s Hospital, School of Medicine, Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
    2 PET Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
    3 Department of Central Laboratory, The Children’s Hospital, School of Medicine, Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
    4 Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
  • Received:2013-02-01 Revised:2013-04-10 Online:2013-06-15 Published:2013-06-15
  • Contact: Zhiyong Hu, M.D., Professor, Department of Anesthesiology, The Children’s Hospital, School of Medicine, Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou 310003, Zhejiang Province, China, huzhiyong777@126.com.
  • About author:Haiyan Jin☆, M.D.

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摘要：

给雄性7日龄Wistar新生鼠腹腔注射40㎎/kg氯胺酮，并于新生鼠出现翻正反射时追加注射3次20㎎/kg氯胺酮，以相同方法注射等量生理盐水的新生鼠作为对照。给药后1,7,14d取材。电镜观察发现，给予氯胺酮的新生鼠海马神经元结构出现明显改变，微管结构排列紊乱。实时定量PCT结果显示，氯胺酮上调新生鼠海马异常磷酸化tau蛋白mRNA的表达。Western blot检测显示，新生鼠海马tau蛋白Ser396位点磷酸化水平于氯胺酮注射后1d降低，之后逐渐升高，至给药后14d高于对照组水平；而海马tau蛋白Ser404位点磷酸化水平在氯胺酮注射后明显升高，随给药时间的延长逐渐降低，但至给药后14d仍明显高于对照组。作者认为，氯胺酮麻醉可使新生鼠海马异常磷酸化Tau蛋白mRNA表达上调，并致tau蛋白Ser404位点过度磷酸化，导致微管排列紊乱，损伤海马神经元。

关键词: 神经再生, 神经退行性变, Tau蛋白, 氯胺酮, 磷酸化, 新生鼠, 海马, 神经元, 麻醉药, 认知, 基金资助文章, 图片文章

Abstract:

Male Wistar 7-day-old rats were injected with 40 mg/kg ketamine intraperitoneally, followed by three additional injections of 20 mg/kg ketamine each upon restoration of the righting reflex. Neonatal rats injected with equivalent volumes of saline served as controls. Hippocampal samples were collected at 1, 7 or 14 days following administration. Electron microscopy showed that neuronal structure changed noticeably following ketamine treatment. Specifically, microtubular structure became irregular and disorganized. Quantitative real time-PCR revealed that phosphorylated tau mRNA was upregulated after ketamine. Western blot analysis demonstrated that phosphorylated tau levels at serine 396 initially decreased at 1 day after ketamine injection, and then gradually returned to control values. At 14 days after injection, levels of phosphorylated tau were higher in the ketamine group than in the control group. Tau protein phosphorylated at serine 404 significantly increased after ketamine injection, and then gradually decreased with time. However, the levels of tau protein at serine 404 were significantly greater in the ketamine group than in the control group until 14 days. The present results indicate that ketamine induces an increase of phosphorylated tau mRNA and excessive phosphorylation of tau protein at serine 404, causing disruption of microtubules in the neonatal rat hippocampus and potentially resulting in damage to hippocampal neurons.