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Involvement of calcitonin gene-related peptide and receptor component protein in experimental autoimmune encephalomyelitis
- Source :
- Journal of Neuroimmunology. 271:18-29
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Calcitonin Gene-Related Peptide (CGRP) inhibits microglia inflammatory activation in vitro. We here analyzed the involvement of CGRP and Receptor Component Protein (RCP) in experimental autoimmune encephalomyelitis (EAE). Alpha-CGRP deficiency increased EAE scores which followed the scale alpha-CGRP null>heterozygote>wild type. In wild type mice, CGRP delivery into the cerebrospinal fluid (CSF) 1) reduced chronic EAE (C-EAE) signs, 2) inhibited microglia activation (revealed by quantitative shape analysis), and 3) did not alter GFAP expression, cell density, lymphocyte infiltration, and peripheral lymphocyte production of IFN-gamma, TNF-alpha, IL-17, IL-2, and IL-4. RCP (probe for receptor involvement) was expressed in white matter microglia, astrocytes, oligodendrocytes, and vascular-endothelial cells: in EAE, also in infiltrating lymphocytes. In relapsing-remitting EAE (R-EAE) RCP increased during relapse, without correlation with lymphocyte density. RCP nuclear localization (stimulated by CGRP in vitro) was I) increased in microglia and decreased in astrocytes (R-EAE), and II) increased in microglia by CGRP CSF delivery (C-EAE). Calcitonin like receptor was rarely localized in nuclei of control and relapse mice. CGRP increased in motoneurons. In conclusion, CGRP can inhibit microglia activation in vivo in EAE. CGRP and its receptor may represent novel protective factors in EAE, apparently acting through the differential cell-specific intracellular translocation of RCP.
- Subjects :
- medicine.medical_specialty
Encephalomyelitis, Autoimmune, Experimental
Quantitative image analysis
Calcitonin Gene-Related Peptide
Freund's Adjuvant
Immunology
Nerve Tissue Proteins
Calcitonin gene-related peptide
Article
Myelin oligodendrocyte glycoprotein
Adrenomedullin
Mice
Neuroinflammation
immune system diseases
Internal medicine
medicine
Animals
Immunology and Allergy
Lymphocytes
Enzyme Inhibitors
Receptor
Cells, Cultured
Mice, Knockout
integumentary system
biology
Microglia
Experimental autoimmune encephalomyelitis
CSF delivery
medicine.disease
Peptide Fragments
nervous system diseases
Mice, Inbred C57BL
Nuclear localization
Disease Models, Animal
Neuropeptide
Endocrinology
medicine.anatomical_structure
Gene Expression Regulation
nervous system
Neurology
Calcitonin
biology.protein
Cytokines
Myelin-Oligodendrocyte Glycoprotein
Neurology (clinical)
Receptors, Calcitonin Gene-Related Peptide
Subjects
Details
- ISSN :
- 01655728
- Volume :
- 271
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroimmunology
- Accession number :
- edsair.doi.dedup.....02d9dc84b38ee5a304ef85a322e19531