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

• Published in: Experimental neurology Vol. 234; no. 2; pp. 521 - 526
• Main Authors: Park, Dongsun, Lee, Hong Jun, Joo, Seong Soo, Bae, Dae-Kwon, Yang, Goeun, Yang, Yun-Hui, Lim, Inja, Matsuo, Akinori, Tooyama, Ikuo, Kim, Yun-Bae, Kim, Seung U.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.04.2012; Elsevier
• Subjects: Acetylcholine - metabolism; AF64A cholinotoxin; Alzheimer disease; Alzheimer Disease - metabolism; Alzheimer Disease - therapy; Animals; Astrocytes - metabolism; Avoidance Learning - physiology; Biological and medical sciences; Brain - metabolism; Brain transplantation; Cell Differentiation - physiology; Cell Movement - physiology; Choline acetyltransferase (ChAT); Choline O-Acetyltransferase - metabolism; Cognition; Cognition Disorders - metabolism; Cognition Disorders - therapy; Cognitive function; Development. Senescence. Regeneration. Transplantation; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Humans; Maze Learning - physiology; Medical sciences; Memory - physiology; Neural stem cell; Neural Stem Cells - metabolism; Neural Stem Cells - transplantation; Neurology; Neurons - metabolism; Rats; Vertebrates: nervous system and sense organs; Choline acetyltransferase (ChAT); AF64A cholinotoxin; Brain transplantation; Cognitive function; Alzheimer disease; Neural stem cell; Human; Acyltransferases; Animal model; Nervous system diseases; Cognitive disorder; Enzyme; Transferases; Stem cell; Central nervous system; Cognition; Transplantation; Choline O-acetyltransferase; Cerebral disorder; Encephalon; Central nervous system disease; Degenerative disease
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2011.12.040

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.