Therapeutic potential of fungal derivatives and vitamin A in an experimental model of multiple sclerosis

• Grant number: 16/23317-8
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2017 - December 31, 2019
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Alexandrina Sartori
• Grantee: Alexandrina Sartori
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Sofia Fernanda Gonçalves Zorzella Pezavento

Abstract

Multiple sclerosis is an autoimmune disease that affects the central nervous system (CNS) and has no cure yet. 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 fungal derivatives and vitamin A can contribute to the improvement of symptoms by modulating the immune response and intestinal microbiota. In this context, the aim of this project is to evaluate the therapeutic potential of two dietary supplements that are fungal derivatives, Goldcell BetaGlucan® and ActiveMOS®, isolated or associated with vitamin A, in experimental autoimmune encephalomyelitis (EAE), which is the animal model used in the study of MS. For this purpose, C57BL/6 mice will receive the compounds (1 mg/day/mouse) by gavage for 14 days before (prophylaxis) or 14 days after (therapy) EAE induction. Clinical parameters (incidence, clinical score and weight loss) will be assessed until the chronic phase (30 days after EAE induction). The effect on peripheral immune response will be investigated in the acute phase (18 days after EAE induction) by determination of cytokine production in culture of axillary and inguinal lymph nodes and characterization of regulatory phenotype in dendritic cells (CD103+) and in T lymphocytes (Foxp3+) in the mesenteric lymph nodes. To elucidate the neuroimmune mechanism involved in protection we will evaluate the presence of inflammatory infiltrates and demyelination areas in lumbar spinal cord samples and T cell subsets (Th1/Th2/Th17/Treg), the parameters of oxidative stress and also the activation of microglia in the CNS (brain and spinal cord). Additionally, we will evaluate whether the administration of these compounds, alone or in combination with vitamin A, alters the intestinal microbiota. If there is modulation of the microbiota, will be conducted microbiota transplantation experiments, from the more effective treatment, to see if protection is associated with the direct modulation of the immune response, by alteration of the microbiota or both. We will also evaluate if fungal derivatives interfere with the activation of dendritic cells in vitro and induce the expansion of regulatory T lymphocytes in vivo. (AU)