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Therapeutic efficacy of the organic selenium /vitamin A association in a relapsing-remitting multiple sclerosis model

Grant number: 19/15980-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2019
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Alexandrina Sartori
Grantee:Marina Bonifácio Denadai
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS).Approximately 85% of patients have relapsing-remitting MS (RRMS) characterized by an initial neurological dysfunction event followed by remission and relapse episodes. Its immunopathogenesis is complex and involves the interplay of distinct autoreactive T cell subsets and innate immune cells, causing inflammatory process and axonal damage. Recently, there have been major advances in the development of disease-modifying treatments and these new approaches include dietary factors. Evidences observed in patients and in experimental models indicate that organic selenium sources and vitamin A (VitA) can contribute to the improvement of symptoms by modulating the immune response and intestinal microbiota.Selenium is an essential trace element that plays an anti-inflammatory and antioxidant role in a healthy organism. VitA enhances induction of Foxp3(+) regulatory T (Treg) cells and inhibits differentiation of Th17 cells, thereby maintaining tolerance in a steady state. Recently, we observed that oral administration of organic selenium compounds is efficient in controlling the experimental autoimmune encephalomyelitis (EAE), that is a widely employed model to study multiple sclerosis. In this context, we propose to investigate if VitA improves the efficacy of a selenizedcarboxylic acid (SCA), that is a precursor of selenized cysteine being developed by Biorigin, a Brazilian company. For this purpose, SJL/J mice will be submitted to EAE induction and 20 days after, during the remission of the first clinical episode, we will initiate the treatment with SCA and VitA by oral route, every other day. The effect on intestinal immune response will be investigated 42 days after EAE induction bycharacterization of regulatory phenotype in dendritic cells (CD103+) and in T lymphocytes (Foxp3+) in the mesenteric lymph nodes and cytokine production in explants from the jejunum and ileum. To elucidate the neuroimmune mechanism involved in protection we will evaluate the T cell subsets (Th1/Th2/Th17/Treg) and also the activation of macrophage and microglia in the CNS. As RRMS is the most common type of MS progression, we expect that this experimental approach could be used as adjuvant therapy in controlling the neuroinflammation associated to this pathology.