Comparison of the therapeutical effects of dexamethasone (a synthetic glucocorticoid analogue), and G1 (a G-coupled estrogen receptor, GPER agonist) on the EAE-induced neuroinflammation

• Grant number: 12/24727-4
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2013
• End date: April 30, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Carolina Demarchi Munhoz
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Multiple sclerosis (MS) is a debilitating neurological and autoimmune disease, characterized by inflammation, demielinization, and neurodegeneration. Neuroinflammation is an important finding in MS pathogenesis, contributing for the progression of the disease. Glial cells (microglia and astrocytes) also have a key role in the progression of MS. Systemic corticosteroids, such as dexamethasone, remain the most established and validated treatment options for MS. Despite women are more prone to develop MS, they show clinical improvement when estrogens, in supraphysiologic dosage, is used. However, an important issue regarding their therapeutic application has been the undesirable estrogenic side effects, such as cell proliferation, thought to be mediated primarily through estrogen nuclear receptor alpha (ER±). In addition, very few studies have investigated the estrogen effects on glial and immune cells and little is known about the molecular pathways this hormone interacts with. Taken that, the first aim of this study is to investigate, in vitro, the role of G1, a G-coupled estrogen receptor - GPER - agonist, on the INFg- and IL17-induced inflammatory response in primary cell cultures from neonate C57BL/6 female mice co-cultured with lymphocytes T cell lineage (D1110) and compare them to those from dexamethasone treatment. Second, we aim to verify the functionality of these in vitro findings at the progression of Experimental autoimmune encephalomyelitis (EAE), the experimental model of MS. With this study, we seek to better understand the molecular mechanisms by which estrogen and glucocorticoids modulate neuroinflammation and to provide either new pharmacological tools or to maximize the therapeutical benefits of those already known about using these hormones. (AU)

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)

RUSSELL, ASHLEY L.; TASKER, JEFFREY G.; LUCION, ALDO B.; FIEDLER, JENNY; MUNHOZ, CAROLINA D.; WU, TAO-YIAO JOHN; DEAK, TERRENCE. Factors promoting vulnerability to dysregulated stress reactivity and stress-related disease. Journal of Neuroendocrinology, v. 30, n. 10, SI, OCT 2018. (12/24727-4, 16/03572-3)

NOVAES, LEONARDO SANTANA; DOS SANTOS, NILTON BARRETO; PERFETTO, JULIANO GENARO; GOOSENS, KI ANN; MUNHOZ, CAROLINA DEMARCHI. Environmental enrichment prevents acute restraint stress-induced anxiety-related behavior but not changes in basolateral amygdala spine density. PSYCHONEUROENDOCRINOLOGY, v. 98, p. 6-10, DEC 2018. (16/03572-3, 12/24727-4, 12/24002-0)

NOVAES, LEONARDO SANTANA; DOS SANTOS, NILTON BARRETO; DRAGUNAS, GUILHERME; PERFETTO, JULIANO GENARO; CARLOS LEZA, JUAN; SCAVONE, CRISTOFORO; MUNHOZ, CAROLINA DEMARCHI. Repeated Restraint Stress Decreases Na,K-ATPase Activity via Oxidative and Nitrosative Damage in the Frontal Cortex of Rats. Neuroscience, v. 393, p. 273-283, NOV 21 2018. (12/24002-0, 12/24727-4, 10/13843-8, 16/03572-3)

DOS SANTOS, NILTON; NOVAES, LEONARDO S.; DRAGUNAS, GUILHERME; RODRIGUES, JENNIFER R.; BRANDAO, WESLEY; CAMARINI, ROSANA; SCHATZMANN PERON, JEAN PIERRE; DEMARCHI MUNHOZ, CAROLINA. High dose of dexamethasone protects against EAE-induced motor deficits but impairs learning/memory in C57BL/6 mice. SCIENTIFIC REPORTS, v. 9, APR 30 2019. (12/24002-0, 16/03572-3, 12/24727-4, 11/18703-2)

NOVAES, LEONARDO S.; DOS SANTOS, NILTON BARRETO; BATALHOTE, RAFAELA F. P.; MALTA, MARILIA BRINATI; CAMARINI, ROSANA; SCAVONE, CRISTOFORO; MUNHOZ, CAROLINA DEMARCHI. Environmental enrichment protects against stress-induced anxiety: Role of glucocorticoid receptor, ERK, and CREB signaling in the basolateral amygdala. Neuropharmacology, v. 113, n. A, p. 457-466, FEB 2017. (12/24727-4, 10/13843-8, 16/03572-3)

MALTA, MARILIA B.; MARTINS, JOELCIMAR; NOVAES, LEONARDO S.; DOS SANTOS, NILTON B.; SITA, LUCIANE; CAMARINI, ROSANA; SCAVONE, CRISTOFORO; BITTENCOURT, JACKSON; MUNHOZ, CAROLINA D.. Norepinephrine and Glucocorticoids Modulate Chronic Unpredictable Stress-Induced Increase in the Type 2 CRF and Glucocorticoid Receptors in Brain Structures Related to the HPA Axis Activation. Molecular Neurobiology, v. 58, n. 10, JUL 2021. (12/24002-0, 16/02224-1, 12/24727-4, 10/52068-0, 10/13843-8, 16/03572-3)

VASCONCELOS, ANDREA RODRIGUES; DOS SANTOS, NILTON BARRETO; SCAVONE, CRISTOFORO; MUNHOZ, CAROLINA DEMARCHI. Nrf2/ARE Pathway Modulation by Dietary Energy Regulation in Neurological Disorders. FRONTIERS IN PHARMACOLOGY, v. 10, FEB 4 2019. (16/07427-8, 12/24727-4)

DUQUE, ERICA DE ALMEIDA; MUNHOZ, CAROLINA DEMARCHI. The Pro-inflammatory Effects of Glucocorticoids in the Brain. FRONTIERS IN ENDOCRINOLOGY, v. 7, JUN 28 2016. (12/24727-4, 10/13932-0)

RUSSELL, ASHLEY L.; TASKER, JEFFREY G.; LUCION, ALDO B.; FIEDLER, JENNY; MUNHOZ, CAROLINA D.; WU, TAO-YIAO JOHN; DEAK, TERRENCE. Factors promoting vulnerability to dysregulated stress reactivity and stress-related disease. Journal of Neuroendocrinology, v. 30, n. 10, p. 13-pg., 2018-10-01. (12/24727-4, 16/03572-3)

NOVAES, LEONARDO S.; DOS SANTOS, NILTON BARRETO; BATALHOTE, RAFAELA F. P.; MALTA, MARILIA BRINATI; CAMARINI, ROSANA; SCAVONE, CRISTOFORO; MUNHOZ, CAROLINA DEMARCHI. Environmental enrichment protects against stress-induced anxiety: Role of glucocorticoid receptor, ERK, and CREB signaling in the basolateral amygdala. Neuropharmacology, v. 113, p. 10-pg., 2017-02-01. (16/03572-3, 10/13843-8, 12/24727-4)