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EAE Research Model of Multiple Sclerosis

EAE Research Model of Multiple Sclerosis Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that results in motor, sensory and cognitive impairment. MS is one of the most common disabling neurological diseases in young adults and is more prevalent in Caucasians of northern European ancestry. The main characteristics of this disease are focal areas of demyelination and infiltration of inflammatory cells in the CNS. Despite numerous studies and experimental trials a complete understanding of the pathogenesis still remains unclear. The disease course is unpredictable and life-long, and affects women more commonly. The etiology of the disease seems to be dependent on genetic and environmental factors, which results in substantial observed variations throughout the course of the disease. Several studies have suggested viral and/or microbial infections as a contributor to the disease. 

It’s most commonly believed that MS is an autoimmune disease in which the body’s own immune system recognizes myelin proteins or myelin related proteins as foreign and marks them for destruction. In the body’s periphery, major histocompatibility complex (MHC) Class II proteins expressed on the surface of antigen presenting cells (APC) mistakenly bind to these proteins. This causes a naïve-T (Th0) cell to bind to the antigen and undergo activation and differentiation. Adhesion molecules and matrix metalloproteinases (MMPs) help T-helper1 (Th1) cells stick and penetrate the blood brain barrier (BBB). Once Th1 cells cross the BBB into the CNS, they engage antigen-MHC complexes and produce pro-inflammatory cytokines leading to damage in the CNS. 

Although no animal model thus far establishes all facets of human MS, Experimental Autoimmune Encephalomyelitis (EAE) models are the most studied for the disease. It’s commonly modeled in rodents such as mice, rats and guinea pigs. The origin of the model is traced to the development of the rabies vaccine when it caused encephalomyopathy in a small percentage of humans who received the vaccine. It was later determined that these vaccines contained myelin antigens which triggered an immune response targeting the myelin of the vaccine recipient. 

Although Th1 cells are an important component in the pathology of the disease, more recent findings suggest that a proinflammatory cascade of Th17 cells, IL-6 and TGF-β in the central nervous system may play a critical role in the pathogenesis of EAE and MS. Continued research will help elucidate the underlying cause, development, and effects of MS. 

MOG-Induced EAE

 MOG is unique in that it creates an encephalitogenic T-cell response and a demyelinating autoantibody response to certain mouse strains. Specifically, the MOG peptide 35-55 is used for disease induction. MOG in C57BL/6 mice together with pertussis toxin will result in a chronic-progressive form of EAE. In addition to paw paralysis, this model is characterized with demyelination both of the spinal cord and the brain. 

Clinical score of combined data from multiple MOG-EAE experiments. Daily clinical examinations are performed on each animal for signs of any neurological symptoms/paralysis. Symptoms are scored and recorded according to a 0-15 scale:


 

PLP-Induced Remitting-Relapsing EAE

PLP is a major protein component of CNS myelin. Sections of PLP, such as 139-151 peptide, are encephalitogenic to certain mouse strains. PLP injected in Swiss Jim Lambert (SJL) mice together with pertussis toxin will lead to remitting- relapsing disease. Relapses are associated with epitope spreading in which T cell reactivity to secondary endogenous peptides that emerge as a consequence of the initial phase of myelin destruction. Remissions are associated with a temporary loss of inflammatory cells from the CNS. 

Clinical score in the PLP-induced EAE model indicating the peaks of disease. The first phase of the disease begins around day 10 and subsides around day 25. On day 40 the relapse begins. 


 

 

MD Biosciences offers highly purified Myelin oligodendrocyte glycoprotein (MOG) and Myelin proteolipid protein (PLP) for the induction of EAE models.

PRODUCT                                                                                            SIZE                        CATALOG NUMBER

MOG 35-55, rodent                                                                              25 mg                     3038001

PLP 139-151, rodent                                                                            15 mg                     301008

References

1. Kap YS, van Driel N, Arends R, et al. Immune modulation by a tolerogenic myelin oligodendrocyte glycoprotein (MOG)10–60 containing fusion protein in the marmoset experimental autoimmune encephalomyelitis model. Clinical and Experimental Immunology. 2015; 180 (1):28-39. 

2. Hultqvist, Malin, et al. "The novel small molecule drug Rabeximod is effective in reducing disease severity of mouse models of autoimmune disorders." Annals of the rheumatic diseases 68.1 (2009): 130-135. 

3. McRae, Bradford L., et al. "Induction of active and adoptive relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein." Journal of neuroimmunology 38.3 (1992): 229-240. 

4. Kuchroo, V. K., et al. "Induction of experimental allergic encephalomyelitis by myelin proteolipid-protein-specific T cell clones and synthetic peptides." Pathobiology 59.5 (1991): 305-312. 

5. Tuohy, V. K., R. A. Sobel, and M. B. Lees. "Myelin proteolipid protein-induced experimental allergic encephalomyelitis. Variations of disease expression in different strains of mice." Journal of immunology 140.6 (1988): 1868-1873.