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Resistin-Inhibited Neural Stem Cell-Derived Astrocyte Differentiation Contributes to Permeability Destruction of the Blood–Brain Barrier

Authors
  • Xiaoying, Liu1
  • Li, Tian1, 2
  • Yu, Shang1
  • Jiusheng, Jiang1
  • Jilin, Zhang1
  • Jiayi, Wei1
  • Dongxin, Liu1
  • Wengang, Fang1
  • Xinyue, Zhao3
  • Hao, Yu3
  • Yuhua, Chen1, 4
  • Deshu, Shang1, 4
  • 1 China Medical University, Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, Ministry of Public Health, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, People’s Republic of China , Shenyang (China)
  • 2 Shengjing Hospital of China Medical University, Deparment of Geriatrics, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, People’s Republic of China , Shenyang (China)
  • 3 China Medical University, Class 81, Phase 102, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, People’s Republic of China , Shenyang (China)
  • 4 China Medical University, Department of Developmental Cell Biology, Cell Biology Division, Key Laboratory of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, Ministry of Public Health, Shenyang, Liaoning, 110122, People’s Republic of China , Shenyang (China)
Type
Published Article
Journal
Neurochemical Research
Publisher
Springer-Verlag
Publication Date
Jan 28, 2019
Volume
44
Issue
4
Pages
905–916
Identifiers
DOI: 10.1007/s11064-019-02726-3
Source
Springer Nature
Keywords
License
Yellow

Abstract

Neuroinflammation is an important part of the development of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s and amyotrophic lateral sclerosis. Inflammatory factors destroy the balance of the microenvironment, which results in changes in neural stem cell differentiation and proliferation behaviour. However, the mechanism underlying inflammatory factor-induced NSC behavioural changes is not clear. Resistin is a proinflammatory and adipogenic factor and is involved in several human pathology processes. The neural stem cell microenvironment changes when the concentration of resistin in the brain during an inflammatory response disease increases. In the present study, we explored the effect and mechanism of resistin on the proliferation and differentiation of neural stem cells. We found that intracerebroventricular injection of resistin induced a decrease in GFAP-positive cells in mice by influencing NSC differentiation. Resistin significantly decreased TEER and increased permeability in an in vitro blood–brain barrier model, which is consistent with the results of an HBMEC-astrocyte coculture system. Resistin-inhibited astrocyte differentiation is mediated through TLR4 on neural stem cells. To our knowledge, this is the first study reporting the effect of resistin on neural stem cells. Our findings shed light on resistin-involved neural stem cell degeneration mechanisms.

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