PMID- 28007537 OWN - NLM STAT- MEDLINE DCOM- 20171227 LR - 20180104 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 320 DP - 2017 Mar 1 TI - Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer's disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis. PG - 291-301 LID - S0166-4328(16)31281-5 [pii] LID - 10.1016/j.bbr.2016.12.021 [doi] AB - Stem cell transplantation represents a promising therapy for central nervous system injuries, but its application to Alzheimer's disease (AD) is still limited and the potential mechanism for cognition improvement remains to be elucidated. In the present study, we used Tg2576 mice which express AD-like pathological forms of amyloid precursor protein (APP) to investigate the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) intravenous transplantation on AD mice. Interestingly, hUC-MSCs transplantation significantly ameliorated cognitive function of AD mice without altering Abeta levels in hippocampus. Remarkably, hUC-MSCs transplantation reduced oxidative stress in hippocampus of AD mice by decreasing the level of malondialdehyde (MDA), increasing the level of nitric oxide (NO), enhancing the activity of superoxide dismutase (SOD) and neuronal nitric oxide synthase (nNOS). The mechanisms underlying the improved cognitive function may be linked to hippocampal neurogenesis and an up-regulation of neuronal synaptic plasticity related proteins levels including silent information regulator 1 (Sirt1), brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN). Taken together, our findings suggest that hUC-MSCs can improve cognition of AD mice by decreasing oxidative stress and promoting hippocampal neurogenesis. These results suggest that modulating hUC-MSCs to generate excess neuroprotective factors could provide a viable therapy to treat AD. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Cui, YuanBo AU - Cui Y AD - Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: cuiyuanbo18@126.com. FAU - Ma, ShanShan AU - Ma S AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: mashanshan84@163.com. FAU - Zhang, ChunYan AU - Zhang C AD - Department of Laboratory, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: biozcy@126.com. FAU - Cao, Wei AU - Cao W AD - Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: caoweiyu@hotmail.com. FAU - Liu, Min AU - Liu M AD - Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: liumin136@126.com. FAU - Li, DongPeng AU - Li D AD - Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China. FAU - Lv, PengJu AU - Lv P AD - Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: pengjulv@163.com. FAU - Xing, Qu AU - Xing Q AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: xingqu163@163.com. FAU - Qu, RuiNa AU - Qu R AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: biorna1881@163.com. FAU - Yao, Ning AU - Yao N AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: yaoning89@126.com. FAU - Yang, Bo AU - Yang B AD - Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China. Electronic address: yangbo96@126.com. FAU - Guan, FangXia AU - Guan F AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: guanfangxia@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161219 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Antigens, CD) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 4.2.1.11 (Phosphopyruvate Hydratase) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Alzheimer Disease/*complications/genetics MH - Amyloid Precursor Protein Secretases/metabolism MH - Amyloid beta-Peptides/metabolism MH - Amyloid beta-Protein Precursor/genetics MH - Animals MH - Antigens, CD/metabolism MH - Bromodeoxyuridine/metabolism MH - *Cognition Disorders/etiology/pathology/surgery MH - Disease Models, Animal MH - Hippocampus/*pathology MH - Humans MH - Maze Learning/physiology MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Neurogenesis/*physiology MH - Nitric Oxide/metabolism MH - Phosphopyruvate Hydratase/metabolism MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - Alzheimer's disease OT - Cognitive function OT - Hippocampal neurogenesis OT - Human umbilical cord mesenchymal stem cells OT - Oxidative stress EDAT- 2016/12/23 06:00 MHDA- 2017/12/28 06:00 CRDT- 2016/12/24 06:00 PHST- 2016/08/26 00:00 [received] PHST- 2016/12/12 00:00 [revised] PHST- 2016/12/16 00:00 [accepted] PHST- 2016/12/23 06:00 [pubmed] PHST- 2017/12/28 06:00 [medline] PHST- 2016/12/24 06:00 [entrez] AID - S0166-4328(16)31281-5 [pii] AID - 10.1016/j.bbr.2016.12.021 [doi] PST - ppublish SO - Behav Brain Res. 2017 Mar 1;320:291-301. doi: 10.1016/j.bbr.2016.12.021. Epub 2016 Dec 19.