中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (4): 394-401.doi: 10.4103/1673-5374.128243

• 原著:退行性病与再生 • 上一篇    下一篇

Tg2576小鼠海马Cajal-Retzius细胞丢失与神经元的淀粉样变

  

  • 收稿日期:2014-01-22 出版日期:2014-02-25 发布日期:2014-02-25

Characterization of hippocampal Cajal-Retzius cells during development in a mouse model of Alzheimer’s disease (Tg2576)

Dongming Yu1, Wenjuan Fan2, Ping Wu1, Jiexin Deng1, Jing Liu1, Yanli Niu1, Mingshan Li1, Jinbo Deng1   

  1. 1 Institute of Neurobiology, School of Life Science, Henan University, Kaifeng, Henan Province, China
    2 Laboratory of Molecular Medicine, Luohe Medical College, Luohe, Henan Province, China
  • Received:2014-01-22 Online:2014-02-25 Published:2014-02-25
  • Contact: Jinbo Deng, Ph.D., Institute of Neurobiology, School of Life Science, Henan University, Kaifeng 475004, Henan Province, China
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 31070952, 81071029; the Joint Funds of the NSFC with Henan Provence Government for Fostering Talents, No. U1204809, and the Henan Province Science Research Project, No. 132102310111.

摘要:

Cajal-Retzius细胞是具有分泌Reelin蛋白功能的神经元,分布在新皮质和海马的边缘区。为了验证Cajal-Retzius细胞和阿尔茨海默病病理之间的关系,实验发现野生型小鼠和瑞典双突变APP695的APPswe转基因小鼠(Tg2576)随着年龄增加海马Cajal-Retzius细胞数量显著降低,Reelin蛋白阳性神经元中活化型caspase-3表达阳性,表明Cajal-Retzius神经元丢失可能与细胞凋亡有关。与对照组相比,Tg2576小鼠海马内Cajal-Retzius细胞数量下降明显,Western Blot证明Tg2576小鼠海马Reelin蛋白水平也比对照组显著下降,且Tg2576小鼠海马Cajal-Retzius细胞数量选择性下降同时伴随有阿尔茨海默病淀粉样病理改变的发生和行为学迹象的改变,表明Cajal-Retzius细胞丢失与阿尔茨海默病脑淀粉样变的发生和发展密切相关。

关键词: 神经再生, 神经退行性变, 阿尔茨海默病, Cajal-Retzius细胞, 海马, 发育, 神经元凋亡, Reelin, Tg2576小鼠, 基金资助文章

Abstract:

Cajal-Retzius cells are reelin-secreting neurons in the marginal zone of the neocortex and hippocampus. The aim of this study was to investigate Cajal-Retzius cells in Alzheimer’s disease pathology. Results revealed that the number of Cajal-Retzius cells markedly reduced with age in both wild type and in mice over-expressing the Swedish double mutant form of amyloid precursor protein 695 (transgenic (Tg) 2576 mice). Numerous reelin-positive neurons were positive for activated caspase 3 in Tg2576 mice, suggesting that Cajal-Retzius neuronal loss occurred via apoptosis in this Alzheimer’s disease model. Compared with wild type, the number of Cajal-Retzius cells was significantly lower in Tg2576 mice. Western blot analysis confirmed that reelin levels were markedly lower in Tg2576 mice than in wild-type mice. The decline in Cajal-Retzius cells in Tg2576 mice was found to occur concomitantly with the onset of Alzheimer’s disease amyloid pathology and related behavioral deficits. Overall, these data indicated that Cajal-Retzius cell loss occurred with the onset and development of Alzheimer’s disease.

Key words: nerve regeneration, neurodegeneration, Alzheimer’s disease, Cajal-Retzius cells, hippocampus, development, neuronal apoptosis, reelin, Tg2576 mice, NSFC grant, neural regeneration