Animal Model of Multiple Sclerosis


Multiple sclerosis is an immune-mediated neurological disorder where the immune system acts on the fatty sheath - myelin sheath. It is a chronic demyelinating disease which affects the nerves in brain and the spinal cord.Rodent models of autoimmune/allergic encephalomyelitis (EAE) is one of the most widely used animal model to study multiple sclerosis. Although it is quite heterogenous and involves a complex induction process, in these animal models of multiple sclerosis T cell reactivity leads to lesions in the central nervous systems including brainstem, cerebellum, optic nerve, spinal cord, and cerebral cortex. These lesions further develop into inflammatory infiltrate leading to gliosis with the demyelination of axons. In some cases of animal models of multiple sclerosis T cell activation may not lead to demyelination.  

Non Invasive Brain Assesments in Pentagrit - Zebrafish Model of Multiple Sclerosis


  1. Burrows DJ, McGown A, Jain SA, et al. Animal models of multiple sclerosis: From rodents to zebrafish. Mult Scler. 2019;25(3):306-324. doi:10.1177/1352458518805246

  2. Wheeler MA, Jaronen M, Covacu R, et al. Environmental Control of Astrocyte Pathogenic Activities in CNS Inflammation. Cell. 2019;176(3):581-596.e18. doi:10.1016/j.cell.2018.12.012

  3. Bose P, Tremblay E, Maois C, et al. The Novel Small Molecule TRVA242 Stabilizes Neuromuscular Junction Defects in Multiple Animal Models of Amyotrophic Lateral Sclerosis. Neurotherapeutics. 2019;16(4):1149-1166. doi:10.1007/s13311-019-00765-w

  4. Osorio-Querejeta I, Sáenz-Cuesta M, Muñoz-Culla M, Otaegui D. Models for Studying Myelination, Demyelination and Remyelination. Neuromolecular Med. 2017;19(2-3):181-192. doi:10.1007/s12017-017-8442-1

  5. Pant DC, Dorboz I, Schluter A, et al. Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy. J Clin Invest. 2019;129(3):1240-1256. doi:10.1172/JCI123959

  6. Procaccini C, De Rosa V, Pucino V, Formisano L, Matarese G. Animal models of Multiple Sclerosis. Eur J Pharmacol. 2015;759:182-191. doi:10.1016/j.ejphar.2015.03.042

  7. Praet J, Guglielmetti C, Berneman Z, Van der Linden A, Ponsaerts P. Cellular and molecular neuropathology of the cuprizone mouse model: clinical relevance for multiple sclerosis. Neurosci Biobehav Rev. 2014;47:485-505. doi:10.1016/j.neubiorev.2014.10.004

  8. Allnoch L, Baumgärtner W, Hansmann F. Impact of Astrocyte Depletion upon Inflammation and Demyelination in a Murine Animal Model of Multiple Sclerosis. Int J Mol Sci. 2019;20(16):3922. Published 2019 Aug 12. doi:10.3390/ijms20163922

  9. Chen Y, Podojil JR, Kunjamma RB, et al. Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis. Brain. 2019;142(2):344-361. doi:10.1093/brain/awy322

  10. van Munster CE, Uitdehaag BM. Outcome Measures in Clinical Trials for Multiple Sclerosis. CNS Drugs. 2017;31(3):217-236. doi:10.1007/s40263-017-0412-5

  11. Inojosa H, Schriefer D, Ziemssen T. Clinical outcome measures in multiple sclerosis: A review. Autoimmun Rev. 2020;19(5):102512. doi:10.1016/j.autrev.2020.102512


Multiple sclerosis animal models such as Transient receptor potential melastatin 2 (TRPM2) knock out (KO) models increases the production of CXCL2 chemokines and lead to neutrophil infiltration playing a central role in the demyelination and immune activity on brain and spinal cord. Animal models of Multiple Sclerosis can also be induced classically through cuprizone a copper chelator that acts on the metalloenzymes such as ceruloplasmin leading to the impairment of copper dependent cytochrome oxidase leading to degenerative oligodendrocytes therefore creating a neuropathology as observed in multiple sclerosis.

In zebrafish models of multiple sclerosis EAE model has been demonstrated by the induction with myelin oligodendrocyte glycoprotein - 35-55 (MOG) or by injecting lysolecithin into the central nervous system of the fry. This leads to a drop in the oligodendrocyte processes for 4 days, with the reducing in myelin sheath in the optic tectum.  Therefore for drug screening, zebrafish models of multiple sclerosis offers a offers window period of 8 days until before when remyelination can occur. Pre-Clinical Models of multiple sclerosis therefore are excellent for studying spontaneous remyelination in vivo as well.

Disability outcomes measure in clinical trials can also be measured in zebrafish model of multiple sclerosis. Zebrafish models of multiple sclerosis can measure optic neuritis, vertigo, motor symptoms, limp ataxia and other sensory symptoms. Therefore clinical equivalence of end points can be derived by quantitative measurements in zebrafish model of Multiple Sclerosis.