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神经干细胞移植可缓解tau蛋白病小鼠模型中的功能性认知缺陷。

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

作者信息

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

机构信息

Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China.

出版信息

Neural Regen Res. 2022 Jan;17(1):152-162. doi: 10.4103/1673-5374.314324.

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.

摘要

神经干细胞(NSCs)移植治疗阿尔茨海默病的机制仍知之甚少。在本研究中,将神经干细胞移植到rTg(tau P301L)4510小鼠模型的海马CA1区,该模型是一种tau蛋白病模型,被认为反映了与阿尔茨海默病相关的tau蛋白病理变化。结果显示,神经干细胞移植减少了tau蛋白的异常聚集,使tau蛋白病模型小鼠的短期记忆有显著改善。与野生型小鼠和接受磷酸盐缓冲盐水(PBS)处理的小鼠相比,接受神经干细胞移植的小鼠脑组织中多种蛋白质的表达发生了变化,尤其是那些与tau蛋白聚集或错误折叠调控相关的蛋白质。京都基因与基因组百科全书(KEGG)通路分析和基因本体(GO)功能分析表明,这些蛋白质主要富集在与长时程增强、神经发生及其他神经生物学过程相关的通路中。关键蛋白表达水平的变化通过蛋白质免疫印迹分析进行了验证。这些数据为增进对神经干细胞移植治疗阿尔茨海默病相关功能能力的理解提供了线索。本研究于2017年获得北京实验动物伦理协会和北京理工大学生命科学学院伦理委员会批准(批准号:SYXK-BIT-生命科学学院-2017-M03)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8f3/8451553/158b49b97e69/NRR-17-152-g002.jpg

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