Immunohistochemical characterization of calcitonin gene-related peptide in the trigeminal system of the familial hemiplegic migraine 1 knock-in mouse

Rammya Mathew, Anna P. Andreou, Linda Chami, Astrid Bergerot, Arn M. J. M. van den Maagdenberg, Michel D. Ferrari, Peter J. Goadsby*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Introduction: Familial hemiplegic migraine type 1 (FHM-1) is caused by mutations in the CACNA1A gene, with the R192Q mutation being the most common. Elevated calcitonin gene-related peptide (CGRP) levels in acute migraine and clinical trials using CGRP receptor antagonists suggest CGRP-related mechanisms are important in migraine.

Methods: Wild-type and R192Q knock-in mice were anaesthetized and perfused. Using immunohistochemical staining, the expression of CGRP in the trigeminocervical complex (TCC) and in the trigeminal and dorsal root ganglia was characterized.

Results: There was a 38% reduction in the percentage of CGRP-immunoreactive cells in the trigeminal ganglia (p <0.001) of R192Q knock-in mice compared to wild-type animals. The size distribution profile of CGRP-immunoreactive cells within the trigeminal ganglia demonstrated no significant difference in cell diameter between the two groups (p >= 0.56). CGRP expression was also reduced in thoracic ganglia of R192Q knock-in mice (21% vs. 27% in wild-type group; p <0.05), but not in other ganglia. In addition, decreased CGRP immunoreactivity was observed in the superficial laminae of the TCC in R192Q knock-in mice, when compared to the control group (p <0.005).

Conclusion: The data demonstrates that the FHM-1 CACNA1A mutation alters CGRP expression in the trigeminal ganglion and TCC. This suggests further study of these animals is warranted to characterize better the role of these mutations in the neurobiology of migraine.

Original languageEnglish
Pages (from-to)1368-1380
Number of pages13
JournalCephalalgia
Volume31
Issue number13
DOIs
Publication statusPublished - Oct 2011

Keywords

  • CACNA1A
  • CGRP
  • migraine
  • R192Q
  • trigeminal system
  • CORTICAL SPREADING DEPRESSION
  • CALCIUM-CHANNELS
  • SUBSTANCE-P
  • NITRIC-OXIDE
  • NUCLEUS CAUDALIS
  • CA2+ CHANNELS
  • NERVE-FIBERS
  • SPINAL-CORD
  • BRAIN-STEM
  • NEURONS

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