PMID- 23731954 OWN - NLM STAT- MEDLINE DCOM- 20140305 LR - 20130812 IS - 1558-1497 (Electronic) IS - 0197-4580 (Linking) VI - 34 IP - 11 DP - 2013 Nov TI - Improvement of cognitive function and physical activity of aging mice by human neural stem cells over-expressing choline acetyltransferase. PG - 2639-46 LID - S0197-4580(13)00194-2 [pii] LID - 10.1016/j.neurobiolaging.2013.04.026 [doi] AB - 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. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Park, Dongsun AU - Park D AD - College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea. FAU - Yang, Yun-Hui AU - Yang YH FAU - Bae, Dae Kwon AU - Bae DK FAU - Lee, Sun Hee AU - Lee SH FAU - Yang, Goeun AU - Yang G FAU - Kyung, Jangbeen AU - Kyung J FAU - Kim, Dajeong AU - Kim D FAU - Choi, Ehn-Kyoung AU - Choi EK FAU - Lee, Seong Won AU - Lee SW FAU - Kim, Gon Hyung AU - Kim GH FAU - Hong, Jin Tae AU - Hong JT FAU - Choi, Kyung-Chul AU - Choi KC FAU - Lee, Hong Jun AU - Lee HJ FAU - Kim, Seung U AU - Kim SU FAU - Kim, Yun-Bae AU - Kim YB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130531 PL - United States TA - Neurobiol Aging JT - Neurobiology of aging JID - 8100437 RN - 0 (Neurofilament Proteins) RN - 0 (Receptors, Cholinergic) RN - 108688-71-7 (neurofilament protein H) RN - EC 2.3.1.6 (Choline O-Acetyltransferase) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/metabolism MH - Aging/pathology/*physiology MH - Animals MH - Brain/enzymology/metabolism MH - Choline O-Acetyltransferase/genetics/*metabolism MH - Cognition Disorders/etiology/*surgery MH - Gene Expression Regulation, Developmental/genetics MH - Humans MH - Male MH - Maze Learning MH - Mice MH - Mice, Inbred ICR MH - Motor Activity/*physiology MH - Neural Stem Cells/*physiology/transplantation MH - Neurofilament Proteins/metabolism MH - Receptors, Cholinergic/genetics/metabolism MH - Time Factors MH - Transfection OTO - NOTNLM OT - Acetylcholine OT - Aging OT - Brain-derived neurotrophic factor OT - Choline acetyltransferase OT - Cognitive function OT - Human neural stem cell OT - Nerve growth factor OT - Physical activity EDAT- 2013/06/05 06:00 MHDA- 2014/03/07 06:00 CRDT- 2013/06/05 06:00 PHST- 2012/10/03 00:00 [received] PHST- 2013/04/18 00:00 [revised] PHST- 2013/04/28 00:00 [accepted] PHST- 2013/06/05 06:00 [entrez] PHST- 2013/06/05 06:00 [pubmed] PHST- 2014/03/07 06:00 [medline] AID - S0197-4580(13)00194-2 [pii] AID - 10.1016/j.neurobiolaging.2013.04.026 [doi] PST - ppublish SO - Neurobiol Aging. 2013 Nov;34(11):2639-46. doi: 10.1016/j.neurobiolaging.2013.04.026. Epub 2013 May 31.