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Intravenous Administration of Human Umbilical Cord Mesenchymal Stem Cells Improves Cognitive Impairments and Reduces Amyloid-Beta Deposition in an AβPP/PS1 Transgenic Mouse Model

Neurochemical Research volume 38, pages 2474–2482 (2013)Cite this article

Abstract

Alzheimer’s disease (AD) is characterized by Amyloid-β (Aβ) deposition in senile plaques in specific areas of the brain and by intraneuronal p-tau accumulation in neurofibrillary tangles. Cumulative evidence supports that oxidative stress is an important factor in the pathogenesis of AD and contributes to Aβ generation. However, there is no effective treatment for AD. Human umbilical cord mesenchymal stem cells (HUMSCs) have potential therapeutic value for the treatment of neurological disease. However, the therapeutic impact of systemic administration of HUMSCs and their mechanism of action in AD have not yet been determined. Here, we found that intravenous infusion of HUMSCs significantly improved spatial learning and alleviated memory decline in an AβPP/PS1 mouse model of AD. HUMSC treatment also increased glutathione (GSH) activity and ratio of GSH to oxidative glutathione as well as superoxide dismutase activity, while decreasing malondialdehyde activity and protein carbonyl level, which suggests that HUMSC infusion alleviated oxidative stress in AβPP/PS1 mice. In addition, HUMSC infusion reduced β-secretase 1 and CTFβ, thus reducing Aβ deposition in mice. HUMSCs may have beneficial effects in the prevention and treatment of AD.

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Acknowledgments

This research was supported by National Basic Research Program of China (2009CB526507), the National Natural Science Foundation of China (No. 81171214), Shandong Province Natural Science Foundation (ZR2011HM064), and the science and technology project of Jinan city (200906011-2), National Natural Science Foundation of China (No. 81371420).

Conflict of interest

All authors declare no conflicts of interest.

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Affiliations

  1. Department of Neurology Medicine, Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China

    Hui Yang, HongNa Yang, ZhaoHong Xie, LiFei Wei, Ping Wang, CuiPing Zhao & JianZhong Bi

  2. Department of Surgery, Liaocheng People’s Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, 252004, People’s Republic of China

    CaiBin Yue

  3. Department of Nephrology Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China

    HongZhen Hu

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  1. Hui Yang
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Correspondence to JianZhong Bi.

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Hui Yang and CaiBin Yue should be considered first authors.

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Yang, H., Yue, C., Yang, H. et al. Intravenous Administration of Human Umbilical Cord Mesenchymal Stem Cells Improves Cognitive Impairments and Reduces Amyloid-Beta Deposition in an AβPP/PS1 Transgenic Mouse Model. Neurochem Res 38, 2474–2482 (2013). https://doi.org/10.1007/s11064-013-1161-6

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  • DOI: https://doi.org/10.1007/s11064-013-1161-6

Keywords

  • AβPP/PS1 mouse
  • Alzheimer’s disease
  • Amyloid-β peptides
  • Mesenchymal stem cells
  • Oxidative stress
  • β-secretase 1