title: 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.
authors.affiliation: Chungbuk National University College of Vetrinary Medicine, Cheongju, Republic of Korea.
authors.forename: Dongsun
authors.initials: D
authors.lastname: Park
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Lee
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Joo
authors.forename: Dae-Kwon
authors.initials: DK
authors.lastname: Bae
authors.forename: Goeun
authors.initials: G
authors.lastname: Yang
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Yang
authors.forename: Inja
authors.initials: I
authors.lastname: Lim
authors.forename: Akinori
authors.initials: A
authors.lastname: Matsuo
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tooyama
authors.forename: Yun-Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003071:Cognition; D003072:Cognition Disorders / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D009474:Neurons / Q000378:metabolism; D051381:Rats
chemical_list: D002795:Choline O-Acetyltransferase; D000109:Acetylcholine