Resistin-Inhibited Neural Stem Cell-Derived Astrocyte Differentiation Contributes to Permeability Destruction of the Blood–Brain Barrier
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.
KeywordsResistin Neural stem cell Astrocyte Permeability Blood–brain barrier
This research was supported by grants from the National Natural Science Foundation of China (Grant Nos. 30600327, 31571057), Liaoning Provincial Department of Education Key Laboratory project (Grant No. LZ2015074), Shenyang Science and Technology Plan Project (Grant Nos. 17-230-9-31 and F16-206-9-03).
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