title: Immunohistochemical characterization of calcitonin gene-related peptide in the trigeminal system of the familial hemiplegic migraine 1 knock-in mouse.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.
authors: University of California San Francisco, San Francisco, 1701 Divisadero St, San Francisco, CA 94115, USA.
authors: Rammya
authors: R
authors: Mathew
authors: Anna P
authors: AP
authors: Andreou
authors: Linda
authors: L
authors: Chami
authors: Astrid
authors: A
authors: Bergerot
authors: Arn Mjm
authors: AM
authors: van den Maagdenberg
authors: Michel D
authors: MD
authors: Ferrari
authors: Peter J
authors: PJ
authors: Goadsby
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001360:Avidin / Q000032:analysis; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000235:genetics; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type / Q000235:genetics* / Q000502:physiology; D020907:Calcium Channels, Q-Type / Q000235:genetics* / Q000502:physiology; D002524:Cerebellar Ataxia / Q000235:genetics*; D003062:Codon / Q000235:genetics; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000032:analysis; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008881:Migraine Disorders / Q000235:genetics*; D023421:Models, Animal; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D017354:Point Mutation; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000166:cytology / Q000378:metabolism*; D014278:Trigeminal Nuclei / Q000166:cytology / Q000378:metabolism*
chemical_list: D001360:Avidin; D015740:Calcitonin Gene-Related Peptide; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D003062:Codon; D016650:Fluorescein-5-isothiocyanate; D009419:Nerve Tissue Proteins; C036963:fluorescein isothiocyante avidin