title: Improvement of cognitive function and physical activity of aging mice by human neural stem cells over-expressing choline acetyltransferase.
abstract: Aging is characterized by progressive loss of cognitive and memory functions as well as decrease in physical activities. In the present study, a human neural stem cell line (F3 NSC) over-expressing choline acetyltransferase (F3.ChAT), an enzyme responsible for acetylcholine synthesis, was generated and transplanted in the brain of 18-month-old male ICR mice. Four weeks post-transplantation, neurobehavioral functions, expression of ChAT enzyme, production of acetylcholine and neurotrophic factors, and expression of cholinergic nervous system markers in transplanted animals were investigated. F3.ChAT NSCs markedly improved both the cognitive function and physical activity of aging animals, in parallel with the elevation of brain acetylcholine level. Transplanted F3 and F3.ChAT cells were found to differentiate into neurons and astrocytes, and to produce ChAT proteins. Transplantation of the stem cells increased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), enhanced expression of Trk B, and restored host microtubule-associated protein 2 and cholinergic nervous system. The results demonstrate that human NSCs over-expressing ChAT improve cognitive function and physical activity of aging mice, not only by producing ACh directly but also by restoring cholinergic neuronal integrity, which might be mediated by neurotrophins BDNF and NGF.
authors.affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Dongsun
authors.initials: D
authors.lastname: Park
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Yang
authors.forename: Dae Kwon
authors.initials: DK
authors.lastname: Bae
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Goeun
authors.initials: G
authors.lastname: Yang
authors.forename: Jangbeen
authors.initials: J
authors.lastname: Kyung
authors.forename: Dajeong
authors.initials: D
authors.lastname: Kim
authors.forename: Ehn-Kyoung
authors.initials: EK
authors.lastname: Choi
authors.forename: Seong Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Gon Hyung
authors.initials: GH
authors.lastname: Kim
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Lee
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Yun-Bae
authors.initials: YB
authors.lastname: Kim
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology / Q000601:surgery*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D008297:Male; D018782:Maze Learning; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology* / Q000637:transplantation; D016900:Neurofilament Proteins / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D016900:Neurofilament Proteins; D011950:Receptors, Cholinergic; C051774:neurofilament protein H; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
keywords: Acetylcholine; Aging; Brain-derived neurotrophic factor; Choline acetyltransferase; Cognitive function; Human neural stem cell; Nerve growth factor; Physical activity