Nox2-dependent Neuroinflammation in An EAE Model of Multiple Sclerosis

• Type of Material: Article
• Authors: Katherine G. Ravelli, University of Sao Paulo; Graziella D. Santos, University of Sao Paulo; Nilton B. dos Santos, University of Sao Paulo; Carolina D. Munhoz, University of Sao Paulo; Deborah Azzi-Nogueira, University of Sao Paulo; Rosana L. Pagano, Hospital Sirio-Libanes; Luiz R. Britto, University of Sao Paulo; Marina Sorrentino Hernandes, Emory University
• Language: English
• Date: 2019-01-01
• Publisher: De Gruyter Open
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Katherine G. Ravelli et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1515/tnsci-2019-0001
• Title of Journal or Parent Work: Translational Neuroscience
• ISSN: 2081-3856
• Volume: 10
• Issue: 1
• Start Page: 1
• End Page: 9
• Grant/Funding Information: Work supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo); University of São Paulo-NAPNA (Núcleo de Apoio à Pesquisa em Neurociência Aplicada) ;and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) ;and American Heart Association.
• Keywords: MICROGLIAL ACTIVATION; CENTRAL-NERVOUS-SYSTEM; NADPH OXIDASE; Neurosciences; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; OXIDATIVE STRESS; astrocytest; Science & Technology; MONONUCLEAR-CELLS; NADPH oxidaset; Neurosciences & Neurology; Multiple sclerosist; Life Sciences & Biomedicine; NITRIC-OXIDE; cytokines; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CEREBROSPINAL-FLUID; EXPRESSION
• Research Categories: Biology, Physiology; Health Sciences, Medicine and Surgery; Biology, Neuroscience

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the CNS, characterized by demyelination, focal inflammatory infiltrates and axonal damage. Oxidative stress has been linked to MS pathology. Previous studies have suggested the involvement of NADPH oxidase 2 (Nox2), an enzyme that catalyzes the reduction of oxygen to produce reactive oxygen species, in the MS pathogenesis. The mechanisms of Nox2 activation on MS are unknown. The purpose of this study was to investigate the effect of Nox2 deletion on experimental autoimmune encephalomyelitis (EAE) onset and severity, on astrocyte activation as well as on pro-inflammatory and anti-inflammatory cytokine induction in striatum and motor cortex. Subcutaneous injection of MOG35-55 emulsified with complete Freund's adjuvant was used to evaluate the effect of Nox2 depletion on EAE-induced encephalopathy. Striatum and motor cortices were isolated and evaluated by immunoblotting and RT-PCR. Nox2 deletion resulted in clinical improvement of the disease and prevented astrocyte activation following EAE induction. Nox2 deletion prevented EAE-induced induction of pro-inflammatory cytokines and stimulated the expression of the anti-inflammatory cytokines IL-4 and IL-10. Our data suggest that Nox2 is involved on the EAE pathogenesis. IL-4 and IL-10 are likely to be involved on the protective mechanism observed following Nox2 deletion.