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Effect of Bushen Yisui Capsule (补肾益髓胶囊) on oligodendrocyte lineage genes 1 and 2 in mice with experimental autoimmune encephalomyelitis

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Abstract

Objective

To study the effects of Bushen Yisui Capsule (补肾益髓胶囊, BSYSC) on the oligodendrocyte lineage genes (Olig) 1 and Olig2 in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE) in order to explore the remyelination effect of BSYSC.

Methods

The mice were randomly divided into normal control (NC), EAE model (EAE-M), prednisone acetate (PA, 6 mg/kg), BSYSC high-dose (3.02 g/kg) and BSYSC low-dose (1.51 g/kg) groups. The mice were induced by immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55. The neurological function scores were assessed once daily. The pathological changes in mice brains were observed with hematoxylin-eosin (HE) staining and transmission electron microscope (TEM). The protein expressions of myelin basic protein (MBP), Olig1 and Olig2 in brains were measured by immunohistochemistry. The mRNA expressions of Olig1 and Olig 2 was also determined by quantitative real-time polymerase chain reaction.

Results

Compared with the EAE-M mice, (1) the neurological function scores were significantly decreased in BSYSC-treated mice on days 22 to 40 (P<0.01); (2) the inflammatory cells and demyelination in brains were reduced in BSYSC-treated EAE mice; (3) the protein expression of MBP was markedly increased in BSYSC-treated groups on day 18 and 40 respectively (P<0.05 or P<0.01); (4) the protein expression of Olig1 was increased in BSYSC (3.02 g/kg)-treated EAE mice on day 40 (P<0.01). Protein and mRNA expression of Olig2 was increased in BSYSC-treated EAE mice on day 18 and 40 (P<0.01).

Conclusion

The effects of BSYSC on reducing demyelination and promoting remyelination might be associated with the increase of Olig1 and Olig2.

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References

  1. Chastain, EM, Miller SD. Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease. Immunol Rev 2012;245:227–238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Herz, J, Zipp F, Siffrin V. Neurodegeneration in autoimmune CNS inflammation. Exp Neurol 2010;225:9–17.

    Article  CAS  PubMed  Google Scholar 

  3. DeLuca GC, Williams K, Evangelou N, Ebers GC, Esiri MM. The contribution of demyelination to axonal loss in multiple sclerosis. Brain 2006;129:1507–1516.

    Article  CAS  PubMed  Google Scholar 

  4. Klistorner A, Garrick R, Paine M, Graham SL, Arvind H, Van Der Walt A, et al. Relationship between chronic demyelination of the optic nerve and short term axonal loss. J. Neurol Neurosurg Psychiatr 2012;83:311–314.

    Article  CAS  PubMed  Google Scholar 

  5. Lidster K, Jackson SJ, Ahmed Z, Munro P, Coffey P, Giovannoni G, et al. Neuroprotection in a novel mouse model of multiple sclerosis. PLoS One 2013;8:e79188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bansal P, Khan T, Bussmeyer U, Challa DK, Swiercz R, Velmurugan R, et al. The encephalitogenic, human myelin oligodendrocyte glycoprotein-induced antibody repertoire is directed toward multiple epitopes in C57BL/6-immunized mice. J Immunol 2013;191:1091–1101.

    Article  CAS  PubMed  Google Scholar 

  7. Van der Star BJ, Vogel DY, Kipp M, Puentes F, Baker D, Amor S. In vitro and in vivo models of multiple sclerosis. CNS Neurol Disord Drug Targets 2012;11:570–588.

    Article  CAS  PubMed  Google Scholar 

  8. Constantinescu CS, Farooqi N, O’Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 2011;164:1079–1106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Deshmukh VA, Tardif V, Lyssiotis CA, Green CC, Kerman B, Kim HJ, et al. A regenerative approach to the treatment of multiple sclerosis. Nature 2013;502:327–332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Nishiyama A, Komitova M, Suzuki R, Zhu X. Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 2009;10:9–22.

    Article  CAS  PubMed  Google Scholar 

  11. Grade S, Bernardino L, Malva JO. Oligodendrogenesis from neural stem cells: perspectives for remyelinating strategies. Int J Dev Neurosci 2013;31:692–700.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang J, Kramer EG, Mahase S, Dutta DJ, Bonnamain V, Argaw AT, et al. Targeting oligodendrocyte protection and remyelination in multiple sclerosis. Mt Sinai J Med 2011;78:244–257.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Van der Walt A, Butzkueven H, Kolbe S, Marriott M, Alexandrou E, Gresle M, et al. Neuroprotection in multiple sclerosis: a therapeutic challenge for the next decade. Pharmacol Ther 2010;126:82–93.

    Article  CAS  PubMed  Google Scholar 

  14. Fan YP, Zhang Q, Zhou L. Reduce of recurrence rates of multiple sclerosis by application of invigorating the kidney in catabasis. China J Tradit Chin Med Pharm (Chin) 2008;23:504–508.

    Google Scholar 

  15. Song LJ, Fan YP. Influence of treatment based on syndrome differentiation mainly with tonifying the kidney on cytokines in plasm of multiple sclerosis at acute stage. China J Tradit Chin Med Pharm (Chin) 2010;25:745–748.

    CAS  Google Scholar 

  16. Wang L, Zhao H, Fan YP, Gong HY, Li M, Qi F, et al. Research on the mechanism of Zuogui Pill and Yougui Pill in promoting axonal regeneration in model rats of autoimmune encephalomyelitis. Chin J Integr Med 2010;16:167–172.

    Article  PubMed  Google Scholar 

  17. Wang YZ, Kou S, Gu LY, Zheng Q, Li M, Qi F, et al. Effects of Zuogui Pill and Yougui Pill on the expression of brain-derived neurotrophic factor and cyclic adenosine monophosphate/ protein kinase a signaling transduction pathways of axonal regeneration in model rats with experimental autoimmune encephalomyelitis. Chin J Integr Med 2014;20:24–30.

    Article  PubMed  Google Scholar 

  18. Liu Y, Zhao H, Zhang J, Zhang P, Li M, Qi F, et al. The regulatory effect of Liuwei Dihuang Pills on cytokines in mice with experimental autoimmune encephalomyelitis. Am J Chin Med 2012;40:295–308.

    Article  PubMed  Google Scholar 

  19. Fan YP, You LZ, Chen KL, Yang T, Wu W. Clinical features and traditional Chinese medicine syndrome types presentation of multiple sclerosis: an analysis of 261 cases. J Capit Univ Med Sci (Chin) 2012;33:301–306.

    Google Scholar 

  20. Li KN, Fan YP, Yang T, Wang L. Mechanism of Erhuang Capsule for treatment of multiple sclerosis. Neural Regen Res 2013;8:523–531.

    PubMed  PubMed Central  Google Scholar 

  21. Fan YP. Treatment of disseminated sclerosis combining disease and syndrome with traditional Chinese medicine. China J Tradit Chin Med Pharm (Chin) 2007;22:289–292.

    Google Scholar 

  22. Taylor AW, Kitaichi N. The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) therapy. Brain Behav Immun 2008;22:639–646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 2005;106:1755–1761.

    Article  CAS  PubMed  Google Scholar 

  24. Fan YP, Wang P, Zhang XH, Gong HY, Zhou L, Liu XZ, et al. Mechanism exploration of Erhuang Formula in treating acute episode of disseminated sclerosis. China J Tradit Chin Med Pharm (Chin) 2007;22:25–29.

    Google Scholar 

  25. Fan YP, Wang P, Zhang XH, Gong HY, Zhou L, Liu XZ, et al. Treatment of relapsing multiple sclerosis with Erhuang Formula. J Beijing Univ Tradit Chin Med (Chin) 2006;29:273–276.

    Google Scholar 

  26. Zhou L, Fan YP, Wang L, Gong HY. Influences of Erhuangfang on cytokines and balance of Th1/Th2 in EAE rats. J Capit Univ Med Sci (Chin) 2009;30:20–23.

    CAS  Google Scholar 

  27. Fan YP, Zhou L, Wang L, Gong HY, Ye M. Influence of Erhuang on the expression of MCP-1 and TNF-α in plasma on acute stage of EAE rat. J Beijing Univ Trad Chin Med (Chin) 2009;28:225–227.

    Google Scholar 

  28. Fan YP, Song LJ, Ye M, Zhou L, Gong HY, Wang L, et al. Influence of Erhuang Capsule on the immunohistochemical expressionof IFN-γ, TGF-β, MMP-9 and Lymphocyte subsets in central nervous system of EAE rat. Chin J Exp Med Formul (Chin) 2010;16:142–146.

    Google Scholar 

  29. Fang L, Zheng Q, Yang T, Zhao H, Zhang QX, Li KN, et al. Bushen Yisui Capsule ameliorates axonal injury in experimental autoimmune encephalomyelitis. Neural Regen Res 2013;35:3306–3315.

    Google Scholar 

  30. Peiris M, Monteith GR, Roberts-Thomson SJ, Cabot PJ. A model of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice for the characterisation of intervention therapies. J Neurosci Methods 2007;163:245–254.

    Article  CAS  PubMed  Google Scholar 

  31. Wilson HC, Scolding NJ, Raine CS. Co-expression of PDGF alpha receptor and NG2 by oligodendrocyte precursors in human CNS and multiple sclerosis lesions. J Neuroimmunol 2006;176:162–173.

    Article  CAS  PubMed  Google Scholar 

  32. Girolamo F, Ferrara G, Strippoli M, Rizzi M, Errede M, Trojano M, et al. Cerebral cortex demyelination and oligodendrocyte precursor response to experimental autoimmune encephalomyelitis. Neurobiol Dis 2011;43:678–689.

    Article  CAS  PubMed  Google Scholar 

  33. Rhodes KE, Raivich G, Fawcett JW. The injury response of oligodendrocyte precursor cells is induced by platelets, macrophages and inflammation-associated cytokines. Neuroscience 2006;140:87–100.

    Article  CAS  PubMed  Google Scholar 

  34. Takebayashi H, Yoshida S, Sugimori M, Kosako H, Kominami R, Nakafuku M, et al. Dynamic expression of basic helix-loop-helix Olig family members: implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3. Mech Dev 2000;99:143–148.

    Article  CAS  PubMed  Google Scholar 

  35. Marie Y, Sanson M, Mokhtari K, Leuraud P, Kujas M, Delattre JY, et al. Olig2 as a specific marker of oligodendroglial tumour cells. Lancet 2001;358:298–300.

    Article  CAS  PubMed  Google Scholar 

  36. Cai J, Chen Y, Cai WH, Hurlock EC, Wu H, Kernie SG, et al. A crucial role for Olig2 in white matter astrocyte development. Development 2007;134:1887–1899.

    Article  CAS  PubMed  Google Scholar 

  37. Mei F, Wang H, Liu S, Niu J, Wang L, He Y, et al. Stagespecific deletion of Olig2 conveys opposing functions on differentiation and maturation of oligodendrocytes. J Neurosci 2013;33:8454–8462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lehner B, Sandner B, Marschallinger J, Lehner C, Furtner T, Couillard-Despres S, et al. The dark side of BrdU in neural stem cell biology: detrimental effects on cell cycle, differentiation and survival. Cell Tissue Res 2001;345:313–328.

    Article  Google Scholar 

  39. Konishi T, Takeyasu A, Natsume T, Furusawa Y, Hieda K. Visualization of heavy ion tracks by labeling 3’-OH termini of induced DNA strand breaks. J Radiat Res 2011;52:433–440.

    Article  CAS  PubMed  Google Scholar 

  40. Meijer DH, Kane MF, Mehta S, Liu H, Harrington E, Taylor CM, et al. Separated at birth? The functional and molecular divergence of Olig1 and Olig2. Nat Rev Neurosci 2012;13:819–831.

    Article  CAS  PubMed  Google Scholar 

  41. Whitman LM, Blanc CA, Schaumburg CS, Rowitch DH, Lane TE. Olig1 function is required for remyelination potential of transplanted neural progenitor cells in a model of viralinduced demyelination. Exp Neurol 2012;235:380–387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cheng X, Wang Y, He Q, Qiu M, Whittemore SR, Cao Q. Bone morphogenetic protein signaling and Olig1/2 interact to regulate the differentiation and maturation of adult oligodendrocyte precursor cells. Stem Cells 2007;25:3204–3214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Niu JQ, Li HL, Xiao L. The role of transcription factors Olig in development of oligodendrocytes and myelin regeneration. Chin J Neuroanat (Chin) 2009;25:591–594.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China

    Tao Yang  (杨 涛), Kang-ning Li  (李康宁) & Yong-ping Fan  (樊永平)

  2. School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100059, China

    Qi Zheng  (郑 琦), Hui Zhao  (赵 晖), Qiu-xia Zhang  (张秋霞), Ming Li  (李 明), Fang Qi  (齐 放), Ling Fang  (房 玲) & Lei Wang  (王 蕾)

  3. Department of Oncology, Guang’anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, 100053, China

    Qi Zheng  (郑 琦)

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  1. Tao Yang  (杨 涛)
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Correspondence to Lei Wang  (王 蕾) or Yong-ping Fan  (樊永平).

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Yang, T., Zheng, Q., Zhao, H. et al. Effect of Bushen Yisui Capsule (补肾益髓胶囊) on oligodendrocyte lineage genes 1 and 2 in mice with experimental autoimmune encephalomyelitis. Chin. J. Integr. Med. 22, 932–940 (2016). https://doi.org/10.1007/s11655-015-2431-8

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  • DOI: https://doi.org/10.1007/s11655-015-2431-8

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