中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (1): 152-162.doi: 10.4103/1673-5374.314324

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

神经干细胞移植改善阿尔茨海默病模型小鼠的认知功能

  

  • 出版日期:2022-01-05 发布日期:2021-09-22

Neural stem cell transplantation alleviates functional cognitive deficits in a mouse model of tauopathy

He-Ao Zhang, Chun-Xu Yuan, Ke-Fu Liu, Qi-Fan Yang, Juan Zhao, Hui Li, Qing-Hu Yang, Da Song, Zhen-Zhen Quan*, Hong Qing*#br#   

  1. Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
  • Online:2022-01-05 Published:2021-09-22
  • Contact: Zhen-Zhen Quan, PhD, qzzbit2015@bit.edu.cn; Hong Qing, PhD, hqing@bit.edu.cn.
  • Supported by:
    This work was supported by the National Key Research and Development Program of China, Nos. 2017YFE0117000 (to ZZQ), 2018YFC1312302-3 (to HQ); the Beijing Advanced Innovation Center for Intelligent Robots and Systems of China, No. 2018IRS12 (to ZZQ); and the National Natural Science Foundation of China, Nos. 82001167 (to HL), 81870844 (to HQ), 81701260 (to ZZQ).

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摘要：

神经干细胞移植治疗阿尔茨海默病的机制尚不十分明确。实验将神经干细胞转染rTg（tau P301L）4510小鼠的海马CA1区，（1）神经干细胞移植减少了tau的异常表达和聚集，且明显改善小鼠的短期记忆障碍；（2）与野生型小鼠和PBS干预的小鼠相比，神经干细胞移植可引发脑组织中大量蛋白，尤其是与调节tau聚集或错误折叠有关蛋白表达的变化；（3）KEGG通路分析和GO功能分析，发现这些蛋白质主要富集于长时程增强、神经发生等神经生物学相关过程，并以western blot对其中的关键蛋白变化情况进行了验证；（4）结果提示移植原代小鼠神经干细胞产生了改善阿尔茨海默病小鼠认知功能的作用。实验于2017年经北京市动物伦理学会和北京理工大学伦理委员会批准（批准号SYXK-BIT-school of life science-2017-M03）。

https://orcid.org/0000-0001-6097-3240 (He-Ao Zhang); https://orcid.org/0000-0002-2557-0371 (Zhen-Zhen Quan); 
https://orcid.org/0000-0003-2820-450X (Hong Qing)

关键词: 神经干细胞, 细胞移植, 阿尔茨海默病, tau蛋白病, 神经分化, 短期记忆, 蛋白组学分析

Abstract: The mechanisms of the transplantation of neural stem cells (NSCs) in the treatment of Alzheimer’s disease remain poorly understood. In this study, NSCs were transplanted into the hippocampal CA1 region of the rTg (tau P301L) 4510 mouse model, a tauopathy model that is thought to reflect the tau pathology associated with Alzheimer’s disease. The results revealed that NSC transplantation reduced the abnormal aggregation of tau, resulting in significant improvements in the short-term memory of the tauopathy model mice. Compared with wild-type and phosphate-buffered saline (PBS)-treated mice, mice that received NSC transplantations were characterized by changes in the expression of multiple proteins in brain tissue, particularly those related to the regulation of tau aggregation or misfolding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) function analysis revealed that these proteins were primarily enriched in pathways associated with long-term potentiation, neurogenesis, and other neurobiological processes. Changes in the expression levels of key proteins were verified by western blot assays. These data provided clues to improve the understanding of the functional capacity associated with NSC transplantation in Alzheimer’s disease treatment. This study was approved by the Beijing Animal Ethics Association and Ethics Committee of Beijing Institute of Technology (approval No. SYXK-BIT-school of life science-2017-M03) in 2017.

Key words: Alzheimer’s disease, cell transplantation, neural differentiation, neural stem cells, proteomic analysis, short-term memory, tauopathy