Neurotoxin-induced animal model of multiple sclerosis: Molecular mechanism focus
DOI:
https://doi.org/10.46542/pe.2024.246.7389Keywords:
Animal model, Multiple sclerosis, Myelin essential protein, Myelin oligodendrocyte glycoproteinAbstract
Background: Neurotoxins can alter the central nervous system. They induce severe clinical symptoms such as encephalopathy, convulsions, muscle paralysis, and respiratory failure. Hence, the neurotoxin can mimic human central nervous system disorders such as Multiple Sclerosis (MS) to study pathophysiology and drugs of development.
Objective: This mini-review compared the neurotoxins for mimicking MS in animal models.
Method: This study was a narrative review using the scientific electronic databases Scopus, PubMed, and Google Scholar. All related articles by keywords animal models, multiple sclerosis, and neurotoxins were collected by YP and BW. All authors contributed to manuscript development.
Result: Cuprizone, ethidium bromide, lysolecithin, Myelin Oligodendrocyte Glycoprotein (MOG), and Myelin Essential Protein (MBP) are neurotoxins for MS animal models. Cuprizone is particularly relevant for use in studies addressing toxic mechanisms of the demyelination process and studies of therapeutic interventions. Ethidium bromide causes spinal cord demyelination with distinctive features in the oligodendrocytes and astrocytes. However, it is a carcinogen agent. Lysolecithin is suitable for old animal models because the duration for remyelination is relatively longer than others. MOG and MBP are preferable to resemble MS pathophysiology in humans.
Conclusion: MOG and MBP are appropriate for generating animal multiple sclerosis models for further in vivo experiments.
References
OpenStax College. (n.d). 7.1: Anatomy of the nervous system - Bbology LibreTexts. (n.d.). Retrieved July 11, 2023, from https://bio.libretexts.org/Courses/Lumen_Learning/Biology_of_Aging_(Lumen)/07%3A_The_Nervous_System/7.01%3A_Anatomy_of_the_Nervous_System
Adams, M. E., & Olivera, B. M. (1994). Neurotoxins: overview of an emerging research technology. Trends in Neurosciences, 17(4), 151–155. https://doi.org/10.1016/0166-2236(94)90092-2
Akassoglou, K. , B. J. , K. G. , P. M. , L. H. , K. G. , & P. L. (1998). Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: Models for multiple sclerosis with primary oligodendrogliopathy. The American Journal of Pathology, 153(3), 801–813.
Akdemir, E. S. , H. A. Y. , & D. B. (2020). Astrocytogenesis: where, when, and how. F1000Research, 9.
Almeida, R. G. , C. T. , F.-C. C. , & L. D. A. (2011). Individual axons regulate the myelinating potential of single oligodendrocytes in vivo. Development (Cambridge, England), 138(20), 4443–4450.
American Association of Neurological Surgeons. (2023). Anatomy of the Brain. Https://Www.Aans.Org/En/Patients/Neurosurgical-Conditions-and-Treatments/Anatomy-of-the-Brain.
Autilio‐Gambetti, L., Sipple, J., Sudilovsky, O., & Gambetti, P. (1982). Intermediate filaments of Schwann cells. Journal of Neurochemistry, 38(3), 774–780. https://doi.org/10.1111/J.1471-4159.1982.TB08698.X
Basoglu, H. A. R. U. N., Boylu, N. T., & KOSE, H. (2013). Cuprizone-induced demyelination in Wistar rats; electrophysiological and histological assessment. European Review for Medical & Pharmacological Sciences, 17(20).
Beeton, C., Wulff, H., Barbaria, J., Clot-Faybesse, O., Pennington, M., Bernard, D., Cahalan, M. D., Chandy, K. G., & Béraud, E. (2001). Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America, 98(24), 13942. https://doi.org/10.1073/PNAS.241497298
Biernacki, T., Sandi, D., Fricska-Nagy, Z., Kincses, Z. T., Füvesi, J., Laczkó, R., Kokas, Z., Klivényi, P., Vécsei, L., & Bencsik, K. (2020). Epidemiology of multiple sclerosis in Central Europe, update from Hungary. Brain and Behavior, 10(5). https://doi.org/10.1002/BRB3.1598
Borisyuk, A., Friedman, A., Ermentrout, B., & Terman, D. (2005). Tutorials in Mathematical Biosciences I. 1860. https://doi.org/10.1007/B102786
Brittis, P. A. , L. Q. , & F. J. G. (2002). Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target. Cell, 2(110), 223–235.
Carota, A., Calabrese, P., & Bogousslavsky, J. (2016). Neurotoxic Weapons and Syndromes. Frontiers of Neurology and Neuroscience, 38, 214–227. https://doi.org/10.1159/000442658
Chayer, C., & Freedman, M. (2001). Frontal lobe functions. Current Neurology and Neuroscience Reports, 1(6), 547–552. https://doi.org/10.1007/S11910-001-0060-4
Christine Beeton, H. W. J. B. O. C.-F. M. P. D. B. M. D. C. K. G. C. and E. B. (2001). Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proceedings of the National Academy of Sciences, 98(24), 13942–13947.
Cristiano, E., Rojas, J. I., Romano, M., Frider, N., MacHnicki, G., Giunta, D. H., Calegaro, D., Corona, T., Flores, J., Gracia, F., MacIas-Islas, M., & Correale, J. (2013). The epidemiology of multiple sclerosis in Latin America and the Caribbean: a systematic review. Multiple Sclerosis (Houndmills, Basingstoke, England), 19(7), 844–854. https://doi.org/10.1177/1352458512462918
de la Rosa, C., Cano, J., & Reinoso-suárez, F. (1985). An electron microscopic study of astroglia and oligodendroglia in the lateral geniculate nucleus of aged rats. Mechanisms of Ageing and Development, 29(3), 267–281. https://doi.org/10.1016/0047-6374(85)90067-3
de Paula Faria, D., de Vries, E. F., Sijbesma, J. W., Buchpiguel, C. A., Dierckx, R. A., & Copray, S. C. (2014). PET imaging of glucose metabolism, neuroinflammation and demyelination in the lysolecithin rat model for multiple sclerosis. Multiple Sclerosis Journal, 20(11), 1443–1452.
de Rosbo, N. K., Mendel, I., & Ben‐Nun, A. (1995). Chronic relapsing experimental autoimmune encephalomyelitis with a delayed onset and an atypical clinical course, induced in PL/J mice by myelin oligodendrocyte glycoprotein (MOG)‐derived peptide: Preliminary analysis of MOG T cell epitopes. European Journal of Immunology, 25(4), 985–993. https://doi.org/10.1002/eji.1830250419
Eskandarieh, S., Heydarpour, P., Minagar, A., Pourmand, S., & Sahraian, M. A. (2016). Multiple sclerosis epidemiology in East Asia, South East Asia and South Asia: A systematic review. Neuroepidemiology, 46(3), 209–221. https://doi.org/10.1159/000444019
ET, O. D. C. (2007). Understanding the Brain: The Birth of a Learning Science. Centre for Educational Research and Innovation.
Gautam, A. (2017). Nerve cells. Encyclopedia of Animal Cognition and Behavior, 1–3. https://doi.org/10.1007/978-3-319-47829-6_1282-1
Gelfand, J. M. (2014). Multiple sclerosis: Diagnosis, differential diagnosis, and clinical presentation. Handbook of Clinical Neurology, 122, 269–290. https://doi.org/10.1016/B978-0-444-52001-2.00011-X
Ghosh, A., Manrique-Hoyos, N., Voigt, A., Schulz, J. B., Kreutzfeldt, M., Merkler, D., & Simons, M. (2011a). Targeted ablation of oligodendrocytes triggers axonal damage. PloS One, 6(7).
Ghosh, A., Manrique-Hoyos, N., Voigt, A., Schulz, J. B., Kreutzfeldt, M., Merkler, D., & Simons, M. (2011b). Targeted ablation of oligodendrocytes triggers axonal damage. PLOS ONE, 6(7), e22735. https://doi.org/10.1371/JOURNAL.PONE.0022735
Goodkin, D. E. (1996). Interferon beta treatment for multiple sclerosis: Persisting questions. Http://Dx.Doi.Org/10.1177/135245859600100605, 1(6), 321–324. https://doi.org/10.1177/135245859600100605
Goudarzvand, M., Choopani, S., Shams, A., Javan, M., Khodaii, Z., Ghamsari, F., Naghdi, N., Piryaei, A., & Haghparast, A. (2016). Focal injection of ethidium bromide as a simple model to study cognitive deficit and its improvement. Basic and Clinical Neuroscience, 7(1), 63. http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4892333/
Guillamón-Vivancos, T., Gómez-Pinedo, U., & Matías-Guiu, J. (2015). Astrocytes in neurodegenerative diseases (I): function and molecular description. Neurologia (Barcelona, Spain), 30(2), 119–129. https://doi.org/10.1016/J.NRL.2012.12.007
Herculano-Houzel, S. (2012). Neuronal scaling rules for primate brains. The primate advantage. Progress in Brain Research, 195, 325–340. https://doi.org/10.1016/B978-0-444-53860-4.00015-5
Hofman, M. A. (2014). Evolution of the human brain: When bigger is better. Frontiers in Neuroanatomy, 8(MAR), 78485. https://doi.org/10.3389/FNANA.2014.00015/BIBTEX
Horwitz, M. S. , E. C. F. , M. D. B. , R. M. , & O. M. B. (1997). Primary demyelination in transgenic mice expressing interferon-γ. Nature Medicine, 3(9), 1037–1041.
Huang, W. J., Chen, W. W., & Zhang, X. (2017). Multiple sclerosis: Pathology, diagnosis and treatments. Experimental and Therapeutic Medicine, 13(6), 3163. https://doi.org/10.3892/ETM.2017.4410
Jaronen, M., W., M. A., & Quintana, F. J. (2022). Protocol for inducing inflammation and acute myelin degeneration in larval zebrafish. STAR Protocols, 3(1).
Jeffery, N. D., & Blakemore, W. F. (1995). Remyelination of mouse spinal cord axons demyelinated by local injection of lysolecithin. Journal of Neurocytology, 24(10), 775–781. https://doi.org/10.1007/BF01191213
Juan Segura-Aguilar. (2001). Mechanisms of degeneration and protection of the dopaminergic system (First Edition).
Kamm, C. P., Uitdehaag, B. M., & Polman, C. H. (2014). Multiple sclerosis: Current knowledge and future outlook. European Neurology, 72(3–4), 132–141. https://doi.org/10.1159/000360528
Khakh, B. S., & Sofroniew, M. V. (2015). Diversity of astrocyte functions and phenotypes in neural circuits. Nature Neuroscience, 18(7), 942–952. https://doi.org/10.1038/NN.4043
Kostrzewa, R. M. (2009). Neurotoxins. Encyclopedia of Neuroscience, 1035–1041. https://doi.org/10.1016/B978-008045046-9.00519-2
Kretzschmar, B., Pellkofer, H., & Weber, M. S. (2016). The use of oral disease-modifying therapies in multiple sclerosis. Current Neurology and Neuroscience Reports, 16(4). https://doi.org/10.1007/S11910-016-0639-4
Kulkarni, P. , Y. S. , M. R. , S. D. , S. U. , & Y. Pn. zebrafish E. model: A. quick in vivo screen for multiple sclerosis. (2017). Novel zebrafish EAE model: A quick in vivo screen for multiple sclerosis. Multiple Sclerosis and Related Disorders, 11, 32–39.
Kuypers, N. J., James, K. T., Enzmann, G. U., Magnuson, D. S. K., & Whittemore, S. R. (2013). Functional consequences of ethidium bromide demyelination of the mouse ventral spinal cord. Experimental Neurology, 247, 615. https://doi.org/10.1016/J.EXPNEUROL.2013.02.014
Laura-Jane Oluich, Jo Anne S. Stratton, Yao Lulu Xing, Sze Woei Ng, Holly S. Cate, Pankaj Sah, François Windels, Trevor J. Kilpatrick, & Tobias D. Merson. (2012). Targeted Ablation of Oligodendrocytes Induces Axonal Pathology Independent of Overt Demyelination. Journal of Neuroscience, 32(24), 8317–8330.
Love, S. (2006). Demyelinating diseases. Journal of Clinical Pathology, 59(11), 1151–1159. https://doi.org/10.1136/JCP.2005.031195
Lu, Q. R., Sun, T., Zhu, Z., Ma, N., Garcia, M., Stiles, C. D., & Rowitch, D. H. (2002). Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell, 109(1), 75–86. https://doi.org/10.1016/S0092-8674(02)00678-5
Lublin, F. D., Coetzee, T., Cohen, J. A., Marrie, R. A., & Thompson, A. J. (2020). The 2013 clinical course descriptors for multiple sclerosis: A clarification. Neurology, 94(24), 1088–1092. https://doi.org/10.1212/WNL.0000000000009636
Lucchinetti, C., Brück, W., Parisi, J., Scheithauer, B., Rodriguez, M., Lassmann, H., & Heterogeneity, L. H. (2000). Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination.
Ludwig, P. E., & Das, J. M. (2023). Histology, glial cells. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK441945/
Matsushima, G. K., & Morell, P. (2001a). The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathology, 11(1), 107–116.
Matsushima, G. K., & Morell, P. (2001b). The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathology, 11(1), 107–116. https://doi.org/10.1111/J.1750-3639.2001.TB00385.X
McLachlan, N. M. , & W. S. J. (2017). The contribution of brainstem and cerebellar pathways to auditory recognition. Frontiers in Psychology, 8(265).
Meinl, E. , K. M. , & H. R. (2006). B lineage cells in the inflammatory central nervous system environment: Migration, maintenance, local antibody production, and therapeutic modulation. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 59(6), 880–892.
Ming, G. li, & Song, H. (2011). Adult neurogenesis in the mammalian brain: Significant answers and significant Questions. Neuron, 70(4), 687. https://doi.org/10.1016/J.NEURON.2011.05.001
Miyamura, S., Matsuo, N., Nagayasu, K., Shirakawa, H., & Kaneko, S. (2019). Myelin Oligodendrocyte Glycoprotein 35-55 (MOG 35-55)-induced experimental autoimmune encephalomyelitis: A model of chronic multiple sclerosis. Bio-Protocol, 9(24). https://doi.org/10.21769/BIOPROTOC.3453
Monaghan, K. L. , & W. E. C. (2020). The role of granulocyte-macrophage colony-stimulating factor in murine models of multiple sclerosis. Cells, 9(3), 611.
Morris, A. D., & Kucenas, S. (2021). A novel lysolecithin model for visualizing damage in vivo in the larval zebrafish spinal cord. Frontiers in Cell and Developmental Biology, 9.
N. D. Jeffery, & W. F. Blakemore. (1995). Remyelination of mouse spinal cord axons demyelinated by local injection of lysolecithin. 24(10), 775–781.
Nathalia Bernardes Teixeira, G. P. A. C. G. F. B. G. P. B. K. D. S. E. B. (2020). Alterations of peripheral nerve excitability in an experimental autoimmune encephalomyelitis mouse model for multiple sclerosis. Journal of Neuroinflammation, 17(1), 1–14.
Obara, M., Szeliga, M., & Albrecht, J. (2008). Regulation of pH in the mammalian central nervous system under normal and pathological conditions: Facts and hypotheses. Neurochemistry International, 52(6), 905–919. https://doi.org/10.1016/J.NEUINT.2007.10.015
Olivia Guy-Evans. (2023, September 22). An easy guide to neuron anatomy with diagrams. Https://Www.Simplypsychology.Org/Neuron.Html.
Oluich, L.-J., Stratton, J. A. S., Xing, Y. L., Ng, S. W., Cate, H. S., Sah, P., Windels, F., Kilpatrick, T. J., & Merson, T. D. (2012). Neurobiology of disease targeted ablation of oligodendrocytes induces axonal pathology independent of overt demyelination. https://doi.org/10.1523/JNEUROSCI.1053-12.2012
Ovanesov, M. V., Ayhan, Y., Wolbert, C., Moldovan, K., Sauder, C., & Pletnikov, M. V. (2008a). Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection. Journal of Neuroinflammation, 5, 50. https://doi.org/10.1186/1742-2094-5-50
Ovanesov, M. V, Ayhan, Y., Wolbert, C., Moldovan, K., Sauder, C., & Pletnikov, M. V. (2008b). Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection. https://doi.org/10.1186/1742-2094-5-50
Rachel H. Woodruff, & Robin J.M. Franklin. (1999). Demyelination and remyelination of the caudal cerebellar peduncle of adult rats following stereotaxic injections of lysolecithin, ethidium bromide, and complement/anti-galactocerebroside: A comparative study. 25(3), 216–228.
Selewski, D. T., Shah, G. V., Segal, B. M., Rajdev, P. A., & Mukherji, S. K. (2010a). Natalizumab (Tysabri). AJNR: American Journal of Neuroradiology, 31(9), 1588. https://doi.org/10.3174/AJNR.A2226
Selewski, D. T., Shah, G. V., Segal, B. M., Rajdev, P. A., & Mukherji, S. K. (2010b). Natalizumab (Tysabri). In American Journal of Neuroradiology (Vol. 31, Issue 9, pp. 1588–1590). https://doi.org/10.3174/ajnr.A2226
Serlin, Y., Shelef, I., Knyazer, B., & Friedman, A. (2015). Anatomy and physiology of the blood-brain barrier. Seminars in Cell & Developmental Biology, 38, 2–6. https://doi.org/10.1016/J.SEMCDB.2015.01.002
Shackelford, T. , & V. J. (2017). Encyclopedia of animal cognition and behavior.
Sidiropoulou, K., Pissadaki, E. K., & Poirazi, P. (2006). Inside the brain of a neuron. EMBO Reports, 7(9), 886. https://doi.org/10.1038/SJ.EMBOR.7400789
Sil, S., & Ghosh, T. (2016). Role of cox-2 mediated neuroinflammation on the neurodegeneration and cognitive impairments in colchicine induced rat model of Alzheimer’s Disease. Journal of Neuroimmunology, 291, 115–124. https://doi.org/10.1016/J.JNEUROIM.2015.12.003
Solaro, C., Gamberini, G., & Masuccio, F. G. (2018). Depression in Multiple Sclerosis: Epidemiology, Aetiology, Diagnosis and Treatment. CNS Drugs, 32(2), 117–133. https://doi.org/10.1007/S40263-018-0489-5
Somogyi, G., Hlatky, D., Spisák, T., Spisák, Z., Nyitrai, G., & Czurkó, A. (2021). Deciphering the scopolamine challenge rat model by preclinical functional MRI. Scientific Reports, 11(1), 1–12. https://doi.org/10.1038/s41598-021-90273-9
Spassky, N., Goujet-Zalc, C., Parmantier, E., Olivier, C., Martinez, S., Ivanova, A., Ikenaka, K., Macklin, W., Cerruti, I., Zalc, B., & Thomas, J. L. (1998). Multiple restricted origin of oligodendrocytes. The Journal of Neuroscience, 18(20), 8331. https://doi.org/10.1523/JNEUROSCI.18-20-08331.1998
Spencer, P. S., & Lein, P. J. (2014). Neurotoxicity. Encyclopedia of Toxicology: Third Edition, 489–500. https://doi.org/10.1016/B978-0-12-386454-3.00169-X
Tanabe, S., Saitoh, S., Miyajima, H., Itokazu, T., & Yamashita, T. (2019). Microglia suppress the secondary progression of autoimmune encephalomyelitis. Glia, 67(9), 1694–1704. https://doi.org/10.1002/GLIA.23640
Taylor, B., Hardcastle, C., & Marsiske, M. (2019). Central nervous system. Encyclopedia of Gerontology and Population Aging, 1–4. https://doi.org/10.1007/978-3-319-69892-2_668-1
Teixeira, N. B., Picolo, G., Giardini, A. C., Boumezbeur, F., Pottier, G., Kuhnast, B., Servent, D., & Benoit, E. (2020). Alterations of peripheral nerve excitability in an experimental autoimmune encephalomyelitis mouse model for multiple sclerosis. Journal of Neuroinflammation, 17(1), 1–14. https://doi.org/10.1186/S12974-020-01936-9/FIGURES/10
Thau, L., Reddy, V., & Singh, P. (2022). Anatomy, central nervous system. BMJ, 1(4293), 478–478. https://doi.org/10.1136/bmj.1.4293.478
Torday, J. S., & Miller, W. B. (2016). On the evolution of the mammalian brain. Frontiers in Systems Neuroscience, 10(APR), 181440. https://doi.org/10.3389/FNSYS.2016.00031/BIBTEX
Tselis, A., Khan, O., & Lisak, R. P. (2007). Glatiramer acetate in the treatment of multiple sclerosis. Neuropsychiatric Disease and Treatment, 3(2), 259. https://doi.org/10.2147/NEDT.2007.3.2.259
Valori Id, M., Jansson, L., & Tienari, P. J. (2021). CD8+ cell somatic mutations in multiple sclerosis patients and controls-Enrichment of mutations in STAT3 and other genes implicated in hematological malignancies. https://doi.org/10.1371/journal.pone.0261002
Wan, E. C. (2020). Cellular and Molecular Mechanisms in the Pathogenesis of Multiple Sclerosis. Cells, 9(10), 2223.
Wang, P., Wang, Y., Zhang, Q., Zhang, H., Li, Z., Liu, X., Kaur, L., & Kumar, M. (2020). Amelioration of cognitive deficits by Spirulina platensis in L-methionine-induced rat model of vascular dementia. Pharmacognosy Magazine, 16(68), 133. https://doi.org/10.4103/pm.pm_438_19
Weber, B., & Barros, L. F. (2015). The Astrocyte: Powerhouse and recycling center. Cold Spring Harbor Perspectives in Biology, 7(12), 20396–20397. https://doi.org/10.1101/CSHPERSPECT.A020396
Wei, D. C., & Morrison, E. H. (2023). Histology, astrocytes. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK545142/
Wyss-Coray, T. (2016). Ageing, neurodegeneration and brain rejuvenation HHS Public Access. https://doi.org/10.1038/nature20411
Yolanda S. Kap, Paul Smith, S. Anwar Jagessar, Ed Remarque, Erwin Blezer, Gustav J, Strijkers, Jon D. Laman;, Rogier Q., Hintzen, Jan Bauer, Herbert P. M. Brok, & Bert A. ‘t Hart. (2008). Fast progression of recombinant human Myelin/Oligodendrocyte Glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis in marmosets is associated with the activation of MOG34–56-specific cytotoxic T cells. The Journal of Immunology, 180(3), 1326–1337.
Zhu, X. Y., Guo, S. Y., Xia, B., Li, C. Q., Wang, L., & Wang, Y. H. (2019). Development of zebrafish demyelination model for evaluation of remyelination compounds and RORγt inhibitors. Journal of Pharmacological and Toxicological Methods, 98.