High dose of dexamethasone protects against EAE-induced motor deficits but impairs learning/memory in C57BL/6 mice
| Autor: | Carolina Demarchi Munhoz, Guilherme Dragunas, Jennifer R Rodrigues, Leonardo S. Novaes, Jean Pierre Schatzmann Peron, Nilton Nascimento Dos Santos, Rosana Camarini, Wesley Nogueira Brandão |
|---|---|
| Přispěvatelé: | Molecular Pharmacology |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Motor Disorders Central nervous system Anti-Inflammatory Agents Fluorescent Antibody Technique lcsh:Medicine Hippocampus Molecular neuroscience Dexamethasone Article Myelin oligodendrocyte glycoprotein Mice 03 medical and health sciences Receptors Glucocorticoid 0302 clinical medicine Glucocorticoid receptor Memory MEDICAMENTO Internal medicine medicine Animals Learning lcsh:Science Neuroinflammation Multidisciplinary biology business.industry Multiple sclerosis lcsh:R Experimental autoimmune encephalomyelitis medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Spinal Cord biology.protein lcsh:Q Memory consolidation Corticosterone business hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) Scientific Reports, 9(1). Nature Publishing Group Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-43217-3 |
| Popis: | Multiple sclerosis (MS) is an autoimmune and neuroinflammatory disease characterized by demyelination of the Central Nervous System. Immune cells activation and release of pro-inflammatory cytokines play a crucial role in the disease modulation, decisively contributing to the neurodegeneration observed in MS and the experimental autoimmune encephalomyelitis (EAE), the widely used MS animal model. Synthetic glucocorticoids, commonly used to treat the MS attacks, have controversial effects on neuroinflammation and cognition. We sought to verify the influence of dexamethasone (DEX) on the EAE progression and on EAE-induced cognitive deficits. In myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced EAE female mice, treated once with DEX (50 mg/kg) or not, on the day of immunization, DEX decreased EAE-induced motor clinical scores, infiltrating cells in the spinal cord and delayed serum corticosterone peak. At the asymptomatic phase (8-day post-immunization), DEX did not protected from the EAE-induced memory consolidation deficits, which were accompanied by increased glucocorticoid receptor (GR) activity and decreased EGR-1 expression in the hippocampus. Blunting hippocampal GR genomic activation with DnGR vectors prevented DEX effects on EAE-induced memory impairment. These data suggest that, although DEX improves clinical signs, it decreases cognitive and memory capacity by diminishing neuronal activity and potentiating some aspects of neuroinflammation in EAE. |
| Databáze: | OpenAIRE |
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