Abstract text (incl. figure legends and references)
Objective
According to the current hypothesis of migraine pathophysiology, attacks are initiated in the hypothalamus, whereafter an activation cascade commences, which results in the activation of the trigeminal nucleus caudalis (TNC) and then trigeminal ganglion (TG). Calcitonin gene-related peptide (CGRP) release from the trigeminal system is thought to play a central role in migraine pathology, supported by the fact that currently available antimigraine drugs act by blocking CGRP signalling. The aim was to perform a preliminary examination of the hypothalamus in migraine-related pathways.
Methods
CGRP release from hypothalamus-containing acute brain slices was examined using an enzyme-linked immunosorbent assay. In addition, we investigated expression levels of Calca (encoding CGRP) and other genes related to dopaminergic pathways in the hypothalamus and the TNC.
Results
An extracellular concentration of 60 mM potassium significantly induced CGRP release, as compared to baseline (p = 0.01, n = 6), whereas application of 100 nM capsaicin did not (p = 0.16, n = 6). Using quantitative real-time polymerase chain reaction (qRT-PCR), we found that Calca was expressed in the hypothalamus, but no difference was observed between male/female mice. Drd2 (encoding the D2 receptor) was the most highly expressed dopamine receptor in both the male and female hypothalamus and TNC, indicating a dominantly inhibitory effect of dopamine in these regions. In addition, results from qRT-PCR demonstrated a tendency towards lower expression levels of Drd2 in the TNC of female mice, as compared to males.
Conclusion
Central CGRP release can be detected from brain slices of mice, but the expression of Calca did not show any male/female difference. However, we found some sex differences in the dopaminergic pathways, suggesting that lower expression levels of Drd2 in females as compared to males could contribute to increased excitability of the TNC.