Human neural stem cells over-expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction
Human neural stem cells over-expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction
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DOI：
10.1016/j.expneurol.2011.12.040
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发表时间：
2012-04-01
影响因子：
5.3
通讯作者：
Kim, Seung U.
中科院分区：
文献类型：
--
作者：
Park, Dongsun;Lee, Hong Jun;Kim, Seung U.
产生了过表达人胆碱乙酰转移酶 (ChAT) 基因的人神经干细胞 (NSC) 系，并将这些 F3.ChAT NSC 移植到大鼠阿尔茨海默病 (AD) 模型中，该模型是通过应用乙基胆碱芥子氮丙啶离子 (AF64A) 诱导的，该离子特异性地使胆碱能神经变性，从而导致记忆缺陷。 AD的显着特征。 F3.ChAT人NSCs移植完全恢复了AF64A动物的学习和记忆功能，并诱导脑脊液（CSF）中乙酰胆碱（ACh）水平升高。移植的F3.ChAT人NSCs被发现迁移到大脑皮层、海马体、纹状体和隔膜等不同脑区，并分化为神经元和星形胶质细胞。本研究表明，过度表达 ChAT 的人类 NSC 的脑移植可改善 AF64A 胆碱毒素诱导的 AD 大鼠模型中复杂的学习和记忆缺陷。 (C) 2012 Elsevier Inc. 保留所有权利。
A human neural stem cell (NSC) line over-expressing human choline acetyltransferase (ChAT) gene was generated and these F3.ChAT NSCs were transplanted into the brain of rat Alzheimer disease (AD) model which was induced by application of ethylcholine mustard aziridinium ion (AF64A) that specifically denatures cholinergic nerves and thereby leads to memory deficit as a salient feature of AD. Transplantation of F3.ChAT human NSCs fully recovered the learning and memory function of AF64A animals, and induced elevated levels of acetylcholine (ACh) in cerebrospinal fluid (CSF). Transplanted F3.ChAT human NSCs were found to migrate to various brain regions including cerebral cortex, hippocampus, striatum and septum, and differentiated into neurons and astrocytes. The present study demonstrates that brain transplantation of human NSCs over-expressing ChAT ameliorates complex learning and memory deficits in AF64A-cholinotoxin-induced AD rat model. (C) 2012 Elsevier Inc. All rights reserved.