Investigation of neuro-inflammatory parameters in a cuprizone induced mouse model of multiple sclerosis
Investigation of neuro-inflammatory parameters in a cuprizone induced mouse model of multiple sclerosis
Cuprizone, copper chelator, treatment of mouse is a toxic model of multiple sclerosis (MS) in which oligodendrocyte death, demyelination and remyelination can be observed. Understanding T and B cell subset as well as their cytokines involved in MS pathogenesis still requires further scrutiny to better understand immune component of MS. The study presented here, aimed to evaluate relevant cytokines, lymphocytes, and gene expressions profiles during demyelination and remyelination in the cuprizone mouse model of MS. Eighty male C57BL/6J mice fed with 0.2% cuprizone for eight weeks. Cuprizone has been removed from the diet in the following eight weeks. Cuprizone treated and control mice sacrificed biweekly, and corpus callosum of the brain was investigated by staining. Lymphocyte cells of mice analyzed by flow cytometry with CD3e, CD11b, CD19, CD80, CD86, CD4, CD25 and FOXP3 antibodies. IFNgamma, IL-1alpha, IL-2, IL-5, IL-6, IL-10, IL-17, TNF-alpha cytokines were analyzed in plasma samples. Neuregulin 1 (Nrg1), ciliary neurotrophic factor (Cntf) and C-X-C chemokine receptor type 4 (Cxcr4) gene expressions in corpus callosum sections of the mice brain were quantified. Histochemistry analysis showed that demyelination began at the fourth week of cuprizone administration and total demyelination occurred at the twelfth week in chronic model. Remyelination occurred at the fourth week of following withdrawal of cuprizone from diet. The level of mature and activated T cells, regulatory T cells, T helper cells and mature B cells increased during demyelination and decreased when cuprizone removed from diet. Further, both type 1 and type 2 cytokines together with the proinflammatory cytokines increased. The level of oligodendrocyte maturation and survival genes showed differential gene expression in parallel to that of demyelination and remyelination. In conclusion, for the first-time, involvement of both cellular immune response and antibody response as well as oligodendrocyte maturation and survival factors having role in demyelination and remyelination of cuprizone mouse model of MS have been shown.
___
- Acs P, Kalman B (2012) Pathogenesis of multiple sclerosis: what can we learn from the cuprizone model. In: Autoimmunity. Springer, pp 403-431.
- Avsar T, Durası İM, Uygunoğlu U, Tütüncü M, Demirci NO et al. (2015). CSF proteomics identifies specific and shared pathways for multiple sclerosis clinical subtypes. PloS one 10:e0122045.
- Disanto G, Berlanga AJ, Handel AE, Para AE, Burrell AM et al.(2010). Heterogeneity in multiple sclerosis: scratching the surface of a complex disease. Autoimmune Diseases 2011: 932351.
- Disanto G, Morahan JM, Barnett MH, Giovannoni G, Ramagopalan SV (2012). The evidence for a role of B cells in multiple sclerosis. Neurology 78: 823-832.
- Fritzsching B, Haas J, König F, Kunz P, Fritzsching E et al. (2011). Intracerebral human regulatory T cells: analysis of CD4+ CD25+ FOXP3+ T cells in brain lesions and cerebrospinal fluid of multiple sclerosis patients. PloS one 6: e17988.
- Gao X, Gillig TA, Ye P, D’Ercole AJ, Matsushima GK et al. (2000). Interferon-γ protects against cuprizone-induced demyelination. Molecular and Cellular Neuroscience 16: 338- 349.
- Goldenberg MM (2012). Multiple sclerosis review. Pharmacy and Therapeutics 37: 175. Grigoriadis N, Ben-Hur T, Karussis D, Milonas I (2004). Axonal damage in multiple sclerosis: a complex issue in a complex disease. Clinical Neurology and Neurosurgery 106: 211-217.
- Hauser SL, Chan JR, Oksenberg JR (2013). Multiple sclerosis: prospects and promise. Annals of Neurology 74: 317-327.
- Hochstrasser T, Jiangshan Z, Rühling S, Schmitz C, Kipp M (2018). Do pre-clinical multiple sclerosis models allow us to measure neurodegeneration and clinical progression? Expert Review of Neurotherapeutics 18: 351-353.
- Jadidi‐Niaragh F, Mirshafiey A (2011). Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scandinavian Journal of Immunology 74: 1-13.
- Jensen MA, Yanowitch RN, Reder AT, White DM, Arnason BG (2010). Immunoglobulin-like transcript 3, an inhibitor of T cell activation, is reduced on blood monocytes during multiple sclerosis relapses and is induced by interferon β-1b. Multiple Sclerosis Journal 16: 30-38.
- Kanekiyo K, Inamori K-i, Kitazume S, Sato K, Maeda J et al. (2013). Loss of branched O-mannosyl glycans in astrocytes accelerates remyelination. The Journal of Neuroscience 33: 10037-10047.
- Lassmann H (2013). Pathology and disease mechanisms in different stages of multiple sclerosis. Journal of the neurological sciences 333: 1-4.
- Lassmann H, Ransohoff RM (2004). The CD4–Th1 model for multiple sclerosis: a crucial re-appraisal. Trends in Immunology 25: 132-137.
- Lee GR (2018). The balance of Th17 versus Treg cells in autoimmunity. International Journal of Molecular Sciences 19: 730.
- Lehmann-Horn K, Kronsbein HC, Weber MS (2013). Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges. Therapeutic Advances in Neurological Disorders 6: 161-173.
- Li JG, Du YM, Yan ZD, Yan J, Zhuansun YX et al. (2016). CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice. Experimental and Therapeutic Medicine 11: 878-884.
- Li M, Hale JS, Rich JN, Ransohoff RM, Lathia JD (2012). Chemokine CXCL12 in neurodegenerative diseases: an SOS signal for stem cell-based repair. Trends in Neurosciences 35: 619-628.
- Li Z, Ju X, Silveira PA, Abadir E, Hsu W-H et al. (2019). CD83: Activation marker for antigen presenting cells and its therapeutic potential. Frontiers in Immunology 10: 1312.
- Lindner M, Heine S, Haastert K, Garde N, Fokuhl J et al. (2008). Sequential myelin protein expression during remyelination reveals fast and efficient repair after central nervous system demyelination. Neuropathology and Applied Neurobiology 34: 105-114.
- Mason JL, Jones JJ, Taniike M, Morell P, Suzuki K et al. (2000). Mature oligodendrocyte apoptosis precedes IGF-1 production and oligodendrocyte progenitor accumulation and differentiation during demyelination/remyelination. Journal of Neuroscience Research 61: 251-262.
- Matsushima GK, Morell P (2001). The Neurotoxicant, Cuprizone, as a Model to Study Demyelination and Remyelination in the Central Nervous System. Brain Pathology 11: 107-116.
- Mei L, Xiong W-C (2008). Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nature Reviews Neuroscience 9: 437-452.
- Newbern J, Birchmeier C (2010) Nrg1/ErbB signaling networks in Schwann cell development and myelination. In: Seminars in Cell & Developmental Biology. Elsevier, pp 922-928.
- Praet J, Guglielmetti C, Berneman Z, Van der Linden A, Ponsaerts P (2014). Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis. Neuroscience & Biobehavioral Reviews 47: 485-505.
- Rich RR, Fleisher TA, Shearer WT, Schroeder Jr HW, Frew AJ et al. (2012) Clinical Immunology E-Book: Principles and Practice. Elsevier Health Sciences
- Robinson AP, Harp CT, Noronha A, Miller SD (2014). The experimental autoimmune encephalomyelitis (EAE) model of MS: utility for understanding disease pathophysiology and treatment. Handbook of Clinical Neurology 122: 173-189.
- Sanadgol N, Golab F, Tashakkor Z, Taki N, Moradi Kouchi S et al. (2017). Neuroprotective effects of ellagic acid on cuprizoneinduced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis. Pharmaceutical Biology 55: 1679-1687.
- Sidman RL, Angeviné JB, Pierce ET (1971) Atlas of the mouse brain and spinal cord. Harvard University Press
- Siva A (2006). The spectrum of multiple sclerosis and treatment decisions. Clinical Neurology and Neurosurgery 108: 333-338.
- Skripuletz T, Lindner M, Kotsiari A, Garde N, Fokuhl J et al. (2008). Cortical demyelination is prominent in the murine cuprizone model and is strain-dependent. The American Journal of Pathology 172: 1053-1061.
- Sospedra M, Martin R (2005). Immunology of multiple sclerosis. Annual Review of Immunology 23: 683-747.
- Stankoff B, Aigrot M-S, Noël F, Wattilliaux A, Zalc B et al. (2002). Ciliary neurotrophic factor (CNTF) enhances myelin formation: a novel role for CNTF and CNTF-related molecules. Journal of Neuroscience 22: 9221-9227.
- Taveggia C, Thaker P, Petrylak A, Caporaso GL, Toews A et al. (2008). Type III neuregulin‐1 promotes oligodendrocyte myelination. Glia 56: 284-293.
- Torkildsen O, Brunborg LA, Myhr KM, Bo L (2008). The cuprizone model for demyelination. Acta neurologica Scandinavica Supplementum 188: 72-76.
- Velanac V, Unterbarnscheidt T, Hinrichs W, Gummert MN, Fischer TM et al. (2012). Bace1 processing of NRG1 type III produces a myelin‐inducing signal but is not essential for the stimulation of myelination. Glia 60: 203-217.
- Venken K, Hellings N, Broekmans T, Hensen K, Rummens J-L et al. (2008). Natural naive CD4+ CD25+ CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. The Journal of Immunology 180: 6411-6420.
- Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004). Loss of functional suppression by CD4+ CD25+ regulatory T cells in patients with multiple sclerosis. The Journal of Experimental Medicine 199: 971-979.
- Vinuesa CG, Linterman MA, Goodnow CC, Randall KL (2010). T cells and follicular dendritic cells in germinal center B‐cell formation and selection. Immunological Reviews 237: 72-89.
- Zhan J, Mann T, Joost S, Behrangi N, Frank M et al. (2020). The cuprizone model: dos and do nots. Cells 9: 843.
- ISSN: 1300-0152
- Yayın Aralığı: Yılda 6 Sayı
- Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler
Investigation of the efficacy of paclitaxel on some miRNAs profiles in breast cancer stem cells
Ümit ZEYBEK, Cem İsmail KÜÇÜKALİ, Elif ERTÜRK, Ferda ARI, Oğuzhan AKGÜN, Engin ULUKAYA
Zhirong WANG, Xiangjie KONG, Ming ZHU, Zhuoqun XU, Jianfeng SHAO
Analyzing differentially expressed genes and pathways of Bex2-deficient mouse lung via RNA-Seq
Noor BAHADAR, Hanif ULLAH, Salah ADLAT, Rajiv KUMAR SAH, May ZUN ZAW MYINT, Zin MAR OO, Fatoumata BINTA BAH, Farooq HAYEL NAGI, Hsu HTOO, Ahmad UD DIN, Xuechao FENG, Yaowu ZHENG
Eda TAHİR TURANLI, Gökhan TERZİOĞLU, Gökçe ÇELİKYAPI ERDEM, Timucin AVŞAR