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Human neural stem cells over-expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction.

Abstract
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.
AuthorsDongsun Park, Hong Jun Lee, Seong Soo Joo, Dae-Kwon Bae, Goeun Yang, Yun-Hui Yang, Inja Lim, Akinori Matsuo, Ikuo Tooyama, Yun-Bae Kim, Seung U Kim
JournalExperimental neurology (Exp Neurol) Vol. 234 Issue 2 Pg. 521-6 (Apr 2012) ISSN: 1090-2430 [Electronic] United States
PMID22245157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Inc. All rights reserved.
Chemical References
  • Choline O-Acetyltransferase
  • Acetylcholine
Topics
  • Acetylcholine (metabolism)
  • Alzheimer Disease (metabolism, therapy)
  • Animals
  • Astrocytes (metabolism)
  • Avoidance Learning (physiology)
  • Brain (metabolism)
  • Cell Differentiation (physiology)
  • Cell Movement (physiology)
  • Choline O-Acetyltransferase (metabolism)
  • Cognition
  • Cognition Disorders (metabolism, therapy)
  • Disease Models, Animal
  • Humans
  • Maze Learning (physiology)
  • Memory (physiology)
  • Neural Stem Cells (metabolism, transplantation)
  • Neurons (metabolism)
  • Rats

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