Involvement of calcitonin gene-related peptide and receptor component protein in experimental autoimmune encephalomyelitis

Claudia Sardi, Laura Zambusi, Annamaria Finardi, Francesca Ruffini, Adviye A. Tolun, Ian M. Dickerson, Marco Righi, Daniele Zacchetti, Fabio Grohovaz, Luciano Provini, Roberto Furlan, Stefano Morara

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)18-29
Number of pages12
JournalJournal of Neuroimmunology
Volume271
Issue number1-2
DOIs
Publication statusPublished - 2014

Keywords

  • CSF delivery
  • Microglia
  • Neuroinflammation
  • Neuropeptides
  • Nuclear localization
  • Quantitative image analysis

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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