Abstract

MACIAS-COSME, Karelia et al. Generation of a murine model of chronic progressive Experimental Autoimmune Encephalomyelitis for molecular pharmacology studies in Multiple Sclerosis. Biotecnol Apl [online]. 2012, vol.29, n.3, pp.169-174. ISSN 1027-2852.

Experimental autoimmune encephalomyelitis (EAE), when induced in syngenic C57BL/6 mice by using myelin oligodendrocyte glycoprotein (MOG), usually exhibits a chronic progressive pattern. This model mimics many of the symptoms and clinical signs typical of multiple sclerosis (MS) in humans. The present work describes specific adjustments to the experimental parameters described in the literature that were necessary when implementing this model under our conditions, demonstrating the presence of EAE in experimental animals by means of clinical evaluations, molecular assays and ultrastructural studies. The disorder was induced by active immunization with peptide MOG35-55 emulsified in Freund's Incomplete Adjuvant supplemented with Mycobacterium tuberculosis, together with two additional administrations of Pertussis toxin. All immunized animals exhibited the typical clinical signs of EAE, with a severity that increased progressively from day 8 post-induction to the end of the evaluation, at day 28 post-induction. The maximum clinical score was 3.5, and the disorder was not reversible. Body weight loss was associated with clinical deterioration at the initial stages of the experiment. From a molecular perspective, it was shown that effector cytokines (mainly IL-17) were positively regulated in the brain of diseased animals. The characteristic ultrastructural changes of MS were also detected; namely, demyelination and axonal damage. The methodology described here enabled the implementation of an animal model that reproduces fundamental aspects of the pathogenesis of MS and is, therefore, highly useful for the study of physiopathological mechanisms, the identification of new pharmacological targets and the evaluation of specific biomolecules with therapeutic purposes.

Keywords : experimental autoimmune encephalomyelitis; myelin oligodendrocyte glycoprotein; demyelination; multiple sclerosis; C57BL/6.

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