Vitamin D, paricalcitol, glibenclamide and clofazimine: therapeutic and immunomodulatory potential in experimental autoimmune encephalomyelitis

• Grant number: 15/06706-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2016
• Effective date (End): February 28, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandrina Sartori
• Grantee: Luiza Ayumi Nishiyama Mimura
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Multiple sclerosis (MS) is a chronic and demyelinating disease of the central nervous system (CNS). MS immunophatogenesis involves Th1, Th17 and Tc autoreactive lymphocytes and also macrophages and microglial cells activation that release many pro-inflammatory mediators and free radicals. Current therapies do not determine disease cure and some subjects are refractory to therapies. Therefore, new alternatives need to be explored. The aim of this project is to investigate the therapeutic and immunododulatory effect of vitamin D3, paricalcitol, glibenclamide and clofazimine in the progression of experimental autoimmune encephalitis (EAE). In vitro experiments will initially be performed to determine the immunomodulatory potential of these substances. We will investigate the effect on pro-and anti-inflammatory cytokines in peritoneal macrophages, spleen cells and microglia (BV-2 strain) cultures. In vivo experiments will be performed in C57BL/6 mice treated with vitamin D3, paricalcitol or glibenclamide in different moments (after the EAE induction, in the early phase and after the first symptoms) to characterize its peripheral and local (SNC) immunomodulatory effects. The clofazimine therapeutic effect will be evaluated in the SJL mice, in the phase of disease reactivation. Most of the evaluations will be done with standard methods already used in the laboratory: ELISA (cytokines), real time PCR/Cytometry (cells subpopulations/phenotype and inflammasome), histopathology (CNS inflammatory infiltration/demyelination) and biochemical tests (oxidative stress).

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MIMURA, LUIZA AYUMI NISHIYAMA; FRAGA-SILVA, THAIS FERNANDA DE CAMPOS; OLIVEIRA, LARISSA RAGOZZO CARDOSO DE; ISHIKAWA, LARISSA LUMI WATANABE; BORIM, PATRICIA APARECIDA; MACHADO, CARLA DE MORAES; JUNIOR, JOSE DE ANCHIETA DE CASTRO E HORTA; FONSECA, DENISE MORAIS DA; SARTORI, ALEXANDRINA. Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy and Comparison with Paricalcitol. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 4, FEB 2021. (15/06706-8, 13/26257-8)

GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA; NISHIYAMA MIMURA, LUIZA AYUMI; DENADAI, MARINA BONIFACIO; FERNANDES DE SOUZA, WILLIAM DANILO; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; SARTORI, ALEXANDRINA. Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis?. NEURAL REGENERATION RESEARCH, v. 17, n. 9, p. 10-pg., 2022-09-01. (13/26257-8, 13/01604-7, 19/15980-7, 15/06706-8, 13/14353-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MIMURA, Luiza Ayumi Nishiyama. Differential therapeutic effect of vitamin D and Paricalcitol on experimental autoimmune encephalomyelitis.. 2019. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.