Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response
- 8 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Acta Pharmacologica Sinica
- Vol. 43 (3), 563-576
- https://doi.org/10.1038/s41401-021-00696-3
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.Keywords
This publication has 48 references indexed in Scilit:
- Osmotic Demyelination: From an Oligodendrocyte to an Astrocyte PerspectiveInternational Journal of Molecular Sciences, 2019
- Effect of the CSF1R inhibitor PLX3397 on remyelination of corpus callosum in a cuprizone‐induced demyelination mouse modelJournal of Cellular Biochemistry, 2019
- CXCL12 has therapeutic value in facial nerve injury and promotes Schwann cells autophagy and migration via PI3K-AKT-mTOR signal pathwayInternational Journal of Biological Macromolecules, 2018
- Cell-based therapeutic strategies for multiple sclerosisBrain, 2017
- Lethal high: acute disseminated encephalomyelitis (ADEM) triggered by toxic effect of synthetic cannabinoidblack mambaBMJ Case Reports, 2017
- Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigraToxicology Letters, 2016
- Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learnedFrontiers in Cellular Neuroscience, 2014
- Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitisJCI Insight, 2009
- Astrocytes in multiple sclerosis: A product of their environmentCellular and Molecular Life Sciences, 2008
- Increased Aβ Peptides and Reduced Cholesterol and Myelin Proteins Characterize White Matter Degeneration in Alzheimer's DiseaseBiochemistry, 2002