title: Human neural stem cells overexpressing choline acetyltransferase restore cognitive function of kainic acid-induced learning and memory deficit animals.
abstract: Alzheimer disease (AD) is a progressive neurodegenerative disease, which is characterized by loss of memory and cognitive function. In AD patients dysfunction of the cholinergic system is the main cause of cognitive disorders, and decreased activity of choline acetyltransferase (ChAT),  an enzyme responsible for acetylcholine (ACh) synthesis, is observed. In the present study we investigated if brain transplantation of human neural stem cells (NSCs) genetically modified to encode ChAT gene improves cognitive function of kainic acid (KA)-induced learning deficit rats. Intrahippocampal  injection of KA to hippocampal CA3 region caused severe neuronal loss, resulting in profound learning and memory deficit. F3.ChAT human NSCs transplanted intracerebroventricularly improved fully the learning and memory function of KA-induced learning deficit animals, in parallel with the elevation  of ACh levels in cerebrospinal fluid. F3.ChAT human NSCs migrated to the KA-induced injury site (CA3) and differentiated into neurons and astrocytes. The present study demonstrates that human NSCs expressing ChAT have lesion-tropic property and improve cognitive function of learning deficit  model rats with hippocampal injury by increasing ACh level.
authors.affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Dongsun
authors.initials: D
authors.lastname: Park
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Joo
authors.forename: Tae Kyun
authors.initials: TK
authors.lastname: Kim
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyomin
authors.initials: H
authors.lastname: Kang
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Lee
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 / Q000201:enzymology / Q000628:therapy; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D007608:Kainic Acid; D007858:Learning; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D058953:Neural Stem Cells / Q000201:enzymology* / Q000637:transplantation*; D055495:Neurogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation
chemical_list: D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D007608:Kainic Acid