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Scutellarin Alleviates Behavioral Deficits in a Mouse Model of Multiple Sclerosis, Possibly Through Protecting Neural Stem Cells

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Abstract

Scutellarin, a flavonoid extracted from an herbal medication (Erigeron breviscapus Hand-Mazz), has been shown to protect neurons against damage and to promote neurogenesis, and thus has therapeutic potential in the treatment of a variety of neurodegenerative diseases. Since neural stem cells (NSCs) could differentiate into myelin-producing oligodendrocytes, we speculate that scutellarin could also be used to treat multiple sclerosis (MS). In the current study, we examined potential effects of scutellarin using a mouse model of MS. Briefly, adult C57BL/6 mice exposed to cuprizone (8 mg/day through diet, for 6 consecutive weeks) randomly received scutellarin (50 mg/kg/day) or vehicle for 10 consecutive days. In the scutellarin-treated group, rotarod testing at the end of the treatment showed significant improvement of motor function (increased time to fall); myelin basic protein (MBP) staining of the corpus callosum revealed decreased demyelination; TUNEL staining followed by Nestin or Sox2 staining revealed increased number of NSCs and decreased rate of NSC apoptosis in the subventricular zone (SVZ) of the lateral ventricles (LV). In a series of experiments using cultured NSCs subjected to cuprizone injury, we confirmed the protective effects of scutellarin. At 30 μM, scutellarin increased the commitment of NSCs to the oligodendrocyte and neuronal lineages, as evidenced by NG2 chondroitin sulfate proteoglycan (NG2) and doublecortin (DCX) staining. Differentiation into astrocytes (as revealed by glial fibrillary acidic protein (GFAP) staining) was decreased. Maturation of the NSCs committed to the oligodendrocyte lineage, as evidenced by oligodendrocyte marker O4 antibody (O4) staining and MBP staining, was also promoted by scutellarin. Further analysis revealed that scutellarin might suppress the phosphorylation of p38 in cuprizone-induced NSCs. In summary, scutellarin could alleviate motor deficits in a mouse model for MS, possibly by inhibiting NSC apoptosis and promoting differentiation of NSCs to myelin-producing oligodendrocytes.

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Acknowledgments

This work was supported by a grant from the Natural Science Foundation (81271326).

Conflict of Interest

The authors declare no conflict of interest.

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    Authors and Affiliations

    1. Key Laboratory of Stem Cells and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan, People’s Republic of China

      Wei-Wei Wang, Lin Lu, Jing Yuan, Shu-Fen Wang & Zhi-Cheng Xiao

    2. Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China

      Wei-Wei Wang & Hong-Miao Zhang

    3. Mental Health Center of Kunming Medical University, Kunming Psychological Crisis Intervention and Research Center, Kunming City, Yunnan Province, People’s Republic of China

      Tian-Hao Bao

    4. Department of Immunology and Stem Cell Laboratories, Monash University, Clayton, VIC, Australia

      Wei-Wei Wang & Zhi-Cheng Xiao

    5. The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China

      Tian-Hao Bao & Wei Miao

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    1. Wei-Wei Wang
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    2. Lin Lu
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    3. Tian-Hao Bao
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    Correspondence to Shu-Fen Wang or Zhi-Cheng Xiao.

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    Wei-Wei Wang, Lin Lu and Tian-Hao Bao contributed equally to this work.

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    Wang, WW., Lu, L., Bao, TH. et al. Scutellarin Alleviates Behavioral Deficits in a Mouse Model of Multiple Sclerosis, Possibly Through Protecting Neural Stem Cells. J Mol Neurosci 58, 210–220 (2016). https://doi.org/10.1007/s12031-015-0660-0

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    • DOI: https://doi.org/10.1007/s12031-015-0660-0

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