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): 1597-1605.doi: 10.3969/j.issn.1673-5374.2013.17.008

• 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:2012-11-06 修回日期:2013-02-28 出版日期:2013-06-15 发布日期:2013-06-15

Neuropeptide Y gene transfection inhibits post-epileptic hippocampal synaptic reconstruction

Fan Zhang1, 2, Wenqing Zhao1, Wenling Li3, Changzheng Dong3, Xinying Zhang3, Jiang Wu3, Na Li3, Chuandong Liang3   

  1. 1 Graduate School, Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
    2 Hebei General Hospital, Shijiazhuang 050071, Hebei Province, China
    3 Department of Neurosurgery, People’s Hospital of Hebei Province, Shijiazhuang 050071, Hebei Province, China
  • Received:2012-11-06 Revised:2013-02-28 Online:2013-06-15 Published:2013-06-15
  • Contact: Wenqing Zhao, Professor, Chief physician, Doctoral supervisor, Graduate School, Hebei Medical University, Shijiazhuang 050011, Hebei Province, China, hbghwenqingzhao@ 126.com.
  • About author:Fan Zhang☆, Studying for doctorate, Associate professor, Associate chief physician.

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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:

Exogenous neuropeptide Y has antiepileptic effects; however, the underlying mechanism and optimal administration method for neuropeptide Y are still unresolved. Previous studies have used intracerebroventricular injection of neuropeptide Y into animal models of epilepsy. In this study, a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene was injected into the lateral ventricle of rats, while the ipsilateral hippocampus was injected with kainic acid to establish the epileptic model. After transfection of neuropeptide Y gene, mossy fiber sprouting in the hippocampal CA3 region of epileptic rats was significantly suppressed, hippocampal synaptophysin (p38) mRNA and protein expression were inhibited, and epileptic seizures were reduced. These experimental findings indicate that a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene reduces mossy fiber sprouting and inhibits abnormal synaptophysin expression, thereby suppressing post-epileptic synaptic reconstruction.

Key words: neural regeneration, gene therapy, neural plasticity, neurodegeneration, recombinant adeno-associated virus vector, neuropeptide Y, epilepsy, kainic acid, synaptic remodeling, mossy fiber sprouting, hippocampus, synaptophysin, neuroregeneration