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Improvement of cognitive function and physical activity of aging mice by human neural stem cells over-expressing choline acetyltransferase
Authors:Dongsun Park  Yun-Hui Yang  Dae Kwon Bae  Sun Hee Lee  Goeun Yang  Jangbeen Kyung  Dajeong Kim  Ehn-Kyoung Choi  Seong Won Lee  Gon Hyung Kim  Jin Tae Hong  Kyung-Chul Choi  Hong Jun Lee  Seung U. Kim  Yun-Bae Kim
Affiliation:1. College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea;2. Department of Information Statistics, Chungbuk National University, Cheongju, Republic of Korea;3. College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea;4. Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Republic of Korea;5. Division of Neurology, Department of Medicine, University of British Columbia Hospital, Vancouver, British Columbia, Canada
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.
Keywords:Aging   Cognitive function   Physical activity   Human neural stem cell   Choline acetyltransferase   Acetylcholine   Nerve growth factor   Brain-derived neurotrophic factor
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