title: Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer's disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis.
abstract: 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 Aβ 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.
authors.affiliation: Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: cuiyuanbo18@126.com.
authors.forename: YuanBo
authors.initials: Y
authors.lastname: Cui
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: mashanshan84@163.com.
authors.forename: ShanShan
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Laboratory, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: biozcy@126.com.
authors.forename: ChunYan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: caoweiyu@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: liumin136@126.com.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
authors.forename: DongPeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou 450007, People's Republic of China. Electronic address: pengjulv@163.com.
authors.forename: PengJu
authors.initials: P
authors.lastname: Lv
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: xingqu163@163.com.
authors.forename: Qu
authors.initials: Q
authors.lastname: Xing
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: biorna1881@163.com.
authors.forename: RuiNa
authors.initials: R
authors.lastname: Qu
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: yaoning89@126.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China. Electronic address: yangbo96@126.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China. Electronic address: guanfangxia@126.com.
authors.forename: FangXia
authors.initials: F
authors.lastname: Guan
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D053829:Amyloid Precursor Protein Secretases; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine
keywords: Alzheimer’s disease; Cognitive function; Hippocampal neurogenesis; Human umbilical cord mesenchymal stem cells; Oxidative stress