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Neuroimmunology in experimental models of Autoimmune Encephalomyelitis and Congenital Zika Syndrome: physiopathogenesis, susceptibility, cellular therapy, vaccination


Diseases of the central nervous system, either autoimmune, degenerative or infectious, are highly complex and debilitating. On one side, the extension of the life expectancy, uncontrolled diets and sedentarism have greatly contributed to the increased prevalence of these diseases on the population, as Alzheimer's, Multiple Sclerosis and Parkinson's Disease. On the other side, the spread of pathogens, mainly viruses that cause hemorrhagic diseases or Encephalitis are of major concern. Viruses as Ebola, Rift Valey, Dengue, Yellow Fever, and more recently Chikungunya and Zika, are great problems for public health, and must be considered as priorities. On both contexts, it is unquestionable the interaction between the central nervous system and the immune system. In fact, the field of neuroimmunology has widely broadened, bringing interesting answers. Now we know that important diseases as Colitis and Diabetes, as well as the Metabolic Syndrome and insulin resistance during Obesity, are well orchestrated by neuroimmune mechanisms. Along with that, it is noteworthy the great importance of the gut microbiota on that. Thus, it is very evident the importance of research in neuroimmunology. This may not only bring important information concerning the physiopathogenesis of the diseases, but also to support further applied approaches, as therapies and vaccines. In this context, in this project, we aim to understand several different aspects of the pathogenesis of the neuroinflammatory diseases using the models of Experimental Autoimmune Encephalomyelitis and the Zika Congenital Syndrome. We search for genes that confer resistance or susceptibility ZIKV infection, as well as for the miRNAs that modulate their expression. On the EAE model, we continue focused on understanding the role of the NMDAR on lymphocytes, studying not only its activation, but its maturation and function on the thymus and lamina propria, respectively. Furthermore, we propose a therapeutic approach to EAE using mesenchymal stem cells, and a vaccine platform against ZIKV, using a DNA plasmid. The results obtained will not only contribute to a better understanding on the pathogenesis of the diseases, but also support applied studies, and then, reduce their impact on the population. (AU)

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Scientific publications (10)
(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)
GIOVANNONI, FEDERICO; BOSCH, IRENE; POLONIO, CAROLINA MANGANELI; TORTI, MARIA F.; WHEELER, MICHAEL A.; LI, ZHAORONG; ROMORINI, LEONARDO; RODRIGUEZ VARELA, MARIA S.; ROTHHAMMER, VEIT; BARROSO, ANDREIA; et al. AHR is a Zika virus host factor and a candidate target for antiviral therapy. NATURE NEUROSCIENCE, v. 23, n. 8, . (17/11828-0, 17/22504-1, 16/07371-2, 17/26170-0)
BRANDAO, W. N.; DE OLIVEIRA, M. G.; ANDREONI, R. T.; NAKAYA, H.; FARIAS, A. S.; PERON, J. P. S.. Neuroinflammation at single cell level: What is new?. Journal of Leukocyte Biology, . (13/08216-2, 18/21934-5, 17/50137-3, 17/26170-0, 12/19278-6, 17/22504-1, 17/21363-5, 18/14933-2, 19/06372-3)
POLONIO, CAROLINA MANGANELI; DE FREITAS, CARLA LONGO; DE OLIVEIRA, MARILIA GARCIA; ROSSATO, CRISTIANO; BRANDAO, WESLEY NOGUEIRA; ZANLUQUI, NAGELA GHABDAN; DE OLIVEIRA, LILIAN GOMES; NISHIYAMA MIMURA, LUIZA AYUMI; BARROS SILVA, MAYSA BRAGA; GARCIA CALICH, VERA LUCIA; et al. Murine endometrial-derived mesenchymal stem cells suppress experimental autoimmune encephalomyelitis depending on indoleamine-2,3-dioxygenase expression. Clinical Science, v. 135, n. 9, p. 1065-1082, . (18/10242-5, 17/22504-1, 17/11828-0, 16/07371-2, 17/26170-0)
OLIVEIRA, LILIAN G.; SCHATZMANN PERON, JEAN PIERRE. Viral receptors for flaviviruses: Not only gatekeepers. Journal of Leukocyte Biology, v. 106, n. 3, SI, p. 695-701, . (16/21259-0, 17/22504-1, 17/26170-0)
BRANDAO, WESLEY NOGUEIRA; ANDERSEN, MONICA LEVY; PALERMO-NETO, JOAO; PERON, JEAN PIERRE; ZAGER, ADRIANO. Therapeutic treatment with Modafinil decreases the severity of experimental autoimmune encephalomyelitis in mice. International Immunopharmacology, v. 75, . (17/26170-0, 13/18921-5, 11/18703-2)
POLONIO, CAROLINA MANGANELI; PERON, JEAN PIERRE SCHATZMANN. ZIKV Infection and miRNA Network in Pathogenesis and Immune Response. Viruses-Basel, v. 13, n. 10, . (19/13731-0, 17/26170-0, 20/06145-4, 17/11828-0, 17/22504-1)
DE MENDONCA-VIEIRA, LEILA RODRIGUES; ANIBAL-SILVA, CONCEICAO ELIDIANNE; MENEZES-NETO, ARMANDO; NEVES AZEVEDO, ELISA DE ALMEIDA; ZANLUQUI, NAGELA GHABDAN; SCHATZMANN PERON, JEAN PIERRE; DE OLIVEIRA FRANCA, RAFAEL FREITAS. Reactive Oxygen Species (ROS) Are Not a Key Determinant for Zika Virus-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells. Viruses-Basel, v. 13, n. 11, . (16/07371-2, 17/22504-1, 17/26170-0)
SILVA-FILHO, JOAO LUIZ; DE OLIVEIRA, LILIAN G.; MONTEIRO, LETICIA; PARISE, PIERINA L.; ZANLUQUI, NAGELA G.; POLONIO, CAROLINA M.; DE FREITAS, CARLA L.; TOLEDO-TEIXEIRA, DANIEL A.; DE SOUZA, WILLIAM M.; BITTENCOURT, NAJARA; et al. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. BRAIN BEHAVIOR AND IMMUNITY, v. 97, p. 260-274, . (17/26908-0, 16/00194-8, 20/02159-0, 16/21259-0, 18/13866-0, 16/12855-9, 17/22062-9, 17/26170-0, 17/11828-0, 17/02402-0, 20/02448-2, 18/13645-3, 16/07371-2)
DE FREITAS, CARLA LONGO; POLONIO, CAROLINA MANGANELI; BRANDAO, WESLEY NOGUEIRA; ROSSATO, CRISTIANO; ZANLUQUI, NAGELA GHABDAN; DE OLIVEIRA, LILIAN GOMES; DE OLIVEIRA, MARILIA GARCIA; EVANGELISTA, LUCILA PIRES; HALPERN, SILVIO; MALUF, MARIANGELA; et al. Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System. STEM CELL REVIEWS AND REPORTS, . (20/06145-4, 16/07371-2, 18/10242-5, 17/11828-0, 17/22504-1, 17/26170-0)

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