Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response
In: Acta Pharmacologica Sinica, Jg. 43 (2021-06-08), S. 563-576
Online
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Zugriff:
Myelin damage and abnormal remyelination processes lead to central nervous system dysfunction. Glial activation-induced microenvironment changes are characteristic features of the diseases with myelin abnormalities. We previously showed that ginsenoside Rg1, a main component of ginseng, ameliorated MPTP-mediated myelin damage in mice, but the underlying mechanisms are unclear. In this study we investigated the effects of Rg1 and mechanisms in cuprizone (CPZ)-induced demyelination mouse model. Mice were treated with CPZ solution (300 mg· kg(−1)· d(−1), ig) for 5 weeks; from week 2, the mice received Rg1 (5, 10, and 20 mg· kg(−1)· d(−1), ig) for 4 weeks. We showed that Rg1 administration dose-dependently alleviated bradykinesia and improved CPZ-disrupted motor coordination ability in CPZ-treated mice. Furthermore, Rg1 administration significantly decreased demyelination and axonal injury in pathological assays. We further revealed that the neuroprotective effects of Rg1 were associated with inhibiting CXCL10-mediated modulation of glial response, which was mediated by NF-κB nuclear translocation and CXCL10 promoter activation. In microglial cell line BV-2, we demonstrated that the effects of Rg1 on pro-inflammatory and migratory phenotypes of microglia were related to CXCL10, while Rg1-induced phagocytosis of microglia was not directly related to CXCL10. In CPZ-induced demyelination mouse model, injection of AAV-CXCL10 shRNA into mouse lateral ventricles 3 weeks prior CPZ treatment occluded the beneficial effects of Rg1 administration in behavioral and pathological assays. In conclusion, CXCL10 mediates the protective role of Rg1 in CPZ-induced demyelination mouse model. This study provides new insight into potential disease-modifying therapies for myelin abnormalities.
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Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response
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Autor/in / Beteiligte Person: | Wang, Sha-Sha ; Chu, Shifeng ; Dong, Yi-Xiao ; Zhang, Zhao ; Chen, Nai-Hong ; Wenbin, He ; Yajuan, Tian ; Du, Yu-Sheng ; Yan, Xu ; Wang, Zhen-Zhen |
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Zeitschrift: | Acta Pharmacologica Sinica, Jg. 43 (2021-06-08), S. 563-576 |
Veröffentlichung: | Springer Science and Business Media LLC, 2021 |
Medientyp: | unknown |
ISSN: | 1745-7254 (print) ; 1671-4083 (print) |
DOI: | 10.1038/s41401-021-00696-3 |
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