Neural Regeneration Research ›› 2013, Vol. 8 ›› Issue (17): 1590-1596.doi: 10.3969/j.issn.1673-5374.2013.17.007

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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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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.