Journal
EXPERIMENTAL NEUROLOGY
Volume 234, Issue 2, Pages 521-526Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2011.12.040
Keywords
Alzheimer disease; AF64A cholinotoxin; Brain transplantation; Choline acetyltransferase (ChAT); Cognitive function; Neural stem cell
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Funding
- Korean National Research Foundation [2009-0094035]
- National Research Foundation of Korea (NRF) [20100026410, 20100023426]
- Canadian Myelin Research Initiative
- Grants-in-Aid for Scientific Research [23300155] Funding Source: KAKEN
- National Research Foundation of Korea [2009-0094035] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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