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Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response.

ABSTRACT: 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.

SUBMITTER: Dong YX

PROVIDER: S-EPMC8888649 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response.

Dong Yi-Xiao YX Chu Shi-Feng SF Wang Sha-Sha SS Tian Ya-Juan YJ He Wen-Bin WB Du Yu-Sheng YS Wang Zhen-Zhen ZZ Yan Xu X Zhang Zhao Z Chen Nai-Hong NH

Acta pharmacologica Sinica 20210608 3

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. Mi ...[more]

PMID: 34103690

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Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response.

Publications

Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response.

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