Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms
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Migraine is a common, polygenic disorder that is characterized by moderate to severe headache attacks. Migraine attacks are commonly treated with triptans, i.e. serotonin receptor agonists. However, triptans are effective in ~ 60% of the population, and the mechanisms of triptans are debated. Here, we aim to expose the mechanisms of triptan using metabolomics and transcriptomics in spontaneous migraine attacks. We collected temporal multi-omics profiles on 24 migraine patients, using samples collected at a migraine attack, 2 h after treatment with a triptan, when headache-free, and after a cold-pressor test. Differential metabolomic analysis was performed to find metabolites associated with treatment. Their effect was further investigated using correlation analysis and a machine learning approach. We found three differential metabolites: cortisol, sumatriptan and glutamine. The change in sumatriptan levels correlated with a change in GNAI1 and VIPR2 gene expression, both known to regulate cAMP levels. Furthermore, we found fatty acid oxidation to be affected, a mechanism known to be involved in migraine but not previously found in relation to triptans. In conclusion, using an integrative approach we find evidence for a role of glutamine, cAMP regulation, and fatty acid oxidation in the molecular mechanisms of migraine and/or the effect of triptans.
Originalsprog | Engelsk |
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Artikelnummer | 12395 |
Tidsskrift | Scientific Reports |
Vol/bind | 13 |
Antal sider | 8 |
ISSN | 2045-2322 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The work was funded by a grant from the Candys foundation ‘CEHEAD’ awarded to prof. Jes Olesen.
Publisher Copyright:
© 2023, The Author(s).
ID: 361847817