Sex differences in expression of CGRP family of receptors and ligands in the rat trigeminal system.

J Headache Pain

Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.

Published: November 2024

AI Article Synopsis

  • Calcitonin gene-related peptide (CGRP) is a significant member of the calcitonin family and is concentrated in the trigeminovascular system (TVS), which is relevant for migraine treatment.
  • The study involved dissection of trigeminal ganglia from male and female rats, assessing the expression of various peptides and their receptors using techniques like immunohistochemistry and RT-qPCR.
  • Results indicated a higher expression of CGRP mRNA in both genders, a notable increase of receptor activity-modifying protein-1 (RAMP1) in females, and the presence of varying peptides and receptors localized in the TG neurons, emphasizing CGRP's crucial role in the TVS.

Article Abstract

Background: Calcitonin gene-related peptide (CGRP) is part of the calcitonin peptide family, which includes calcitonin (CT), amylin (AMY), and adrenomedullin (ADM). CGRP and its receptor are highly present in the trigeminovascular system (TVS). Recent research suggests that other members of the calcitonin family could be feasible therapeutic targets in the treatment of migraine. The present study aims to elucidate the distribution of ADM, AMY, CT, and their receptors in the rat TVS, and to explore potential sex differences in their expression.

Methods: Trigeminal ganglia (TG) were dissected from male and female adult rats. Protein and gene expression were assessed through immunohistochemistry and RT-qPCR. Additionally, the dura mater was isolated for further investigation of protein expression and fiber localization using immunohistochemistry.

Results: Quantitative gene expression analysis revealed the presence of all genes in male and female TGs, except for calcitonin receptor (CTR). Notably, CGRP mRNA levels in TG were several folds higher than those of other genes. The receptor activity-modifying protein-1 (RAMP1) mRNA levels were significantly higher in female compared to male. No AMY or CT immunoreactivity was observed in the TVS. In contrast, immunoreactivity for ADM, CGRP, RAMP1, CTR, and calcitonin-like receptor (CLR) were observed in the cytoplasm of TG neurons. Immunoreactive Aδ-fibers storing RAMP1, ADM and CLR were also identified. RAMP2 and RAMP3 were expressed in nucleus of TG neurons and in satellite glial cells. Furthermore, RAMP1 and CLR were co-localized with CASPR in the nodes of Ranvier located in Aδ-fibers.

Conclusions: This study provides valuable insights into the distribution of the CGRP family of peptides and their receptors in the TVS. CGRP mRNA levels in the TG were markedly higher than those of other genes, demonstrating the key role of CGRP. The co-localization of CLR and RAMP1 on Aδ-fibers with CASPR suggests a potential role for this receptor in modulating trigeminal nerve function and neuronal excitability, with implications for migraine pathophysiology. Additionally, RAMP1 mRNA levels were significantly higher in female TG compared to males, indicating sex-specific differences in gene expression. These findings underscore the need for further research into the functional significance of gender-related variations.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545840PMC
http://dx.doi.org/10.1186/s10194-024-01893-1DOI Listing

Publication Analysis

Top Keywords

mrna levels
16
gene expression
12
sex differences
8
cgrp
8
cgrp family
8
adm cgrp
8
male female
8
cgrp mrna
8
higher genes
8
ramp1 mrna
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!