Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms
© 2023. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Scientific reports - 13(2023), 1 vom: 31. Juli, Seite 12395 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kogelman, Lisette J A [VerfasserIn] |
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| Links: |
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| Themen: |
0RH81L854J |
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| Anmerkungen: |
Date Completed 03.08.2023 Date Revised 03.08.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-023-38904-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360245714 |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Sumatriptan |2 NLM | |
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| 700 | 1 | |a Falkenberg, Katrine |e verfasserin |4 aut | |
| 700 | 1 | |a Ottosson, Filip |e verfasserin |4 aut | |
| 700 | 1 | |a Ernst, Madeleine |e verfasserin |4 aut | |
| 700 | 1 | |a Russo, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Stentoft-Hansen, Valdemar |e verfasserin |4 aut | |
| 700 | 1 | |a Demharter, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Tfelt-Hansen, Peer |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Arieh S |e verfasserin |4 aut | |
| 700 | 1 | |a Olesen, Jes |e verfasserin |4 aut | |
| 700 | 1 | |a Hansen, Thomas Folkmann |e verfasserin |4 aut | |
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