Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer's disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis

Yuan Bo Cui, Shan Shan Ma, Chun Yan Zhang, Wei Cao, Min Liu, Dong Peng Li, Peng Ju Lv, Qu Xing, Rui Na Qu, Ning Yao, Bo Yang, Fangxia Guan

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)291-301
Number of pages11
JournalBehavioural Brain Research
Volume320
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

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Mesenchymal Stem Cell Transplantation
Umbilical Cord
Neurogenesis
Cognition
Alzheimer Disease
Oxidative Stress
Neuronal Plasticity
Mesenchymal Stromal Cells
Hippocampus
Nervous System Trauma
Nitric Oxide Synthase Type I
Synaptophysin
Amyloid beta-Protein Precursor
Brain-Derived Neurotrophic Factor
Stem Cell Transplantation
Malondialdehyde
Superoxide Dismutase
Nitric Oxide
Up-Regulation
Central Nervous System

Keywords

  • Alzheimer's disease
  • Cognitive function
  • Hippocampal neurogenesis
  • Human umbilical cord mesenchymal stem cells
  • Oxidative stress

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer's disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis. / Cui, Yuan Bo; Ma, Shan Shan; Zhang, Chun Yan; Cao, Wei; Liu, Min; Li, Dong Peng; Lv, Peng Ju; Xing, Qu; Qu, Rui Na; Yao, Ning; Yang, Bo; Guan, Fangxia.

In: Behavioural Brain Research, Vol. 320, 01.03.2017, p. 291-301.

Research output: Contribution to journalArticle

Cui, Yuan Bo ; Ma, Shan Shan ; Zhang, Chun Yan ; Cao, Wei ; Liu, Min ; Li, Dong Peng ; Lv, Peng Ju ; Xing, Qu ; Qu, Rui Na ; Yao, Ning ; Yang, Bo ; Guan, Fangxia. / Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer's disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis. In: Behavioural Brain Research. 2017 ; Vol. 320. pp. 291-301.
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