Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms
Abstract 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 debate...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38904-1 |
| _version_ | 1797752738064367616 |
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| author | Lisette J. A. Kogelman Katrine Falkenberg Filip Ottosson Madeleine Ernst Francesco Russo Valdemar Stentoft-Hansen Samuel Demharter Peer Tfelt-Hansen Arieh S. Cohen Jes Olesen Thomas Folkmann Hansen |
| author_facet | Lisette J. A. Kogelman Katrine Falkenberg Filip Ottosson Madeleine Ernst Francesco Russo Valdemar Stentoft-Hansen Samuel Demharter Peer Tfelt-Hansen Arieh S. Cohen Jes Olesen Thomas Folkmann Hansen |
| author_sort | Lisette J. A. Kogelman |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T17:08:51Z |
| format | Article |
| id | doaj.art-019b32d50c554687bdf123c45787a1b2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T17:08:51Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-019b32d50c554687bdf123c45787a1b22023-08-06T11:11:50ZengNature PortfolioScientific Reports2045-23222023-07-011311810.1038/s41598-023-38904-1Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanismsLisette J. A. Kogelman0Katrine Falkenberg1Filip Ottosson2Madeleine Ernst3Francesco Russo4Valdemar Stentoft-Hansen5Samuel Demharter6Peer Tfelt-Hansen7Arieh S. Cohen8Jes Olesen9Thomas Folkmann Hansen10Department of Neurology, Danish Headache Center, Copenhagen University HospitalDepartment of Neurology, Danish Headache Center, Copenhagen University HospitalDepartment of Congenital Disorders, Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Statens Serum InstitutDepartment of Congenital Disorders, Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Statens Serum InstitutDepartment of Congenital Disorders, Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Statens Serum InstitutAbzu ApSAbzu ApSDepartment of Neurology, Danish Headache Center, Copenhagen University HospitalDepartment of Congenital Disorders, Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Statens Serum InstitutDepartment of Neurology, Danish Headache Center, Copenhagen University HospitalDepartment of Neurology, Danish Headache Center, Copenhagen University HospitalAbstract 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.https://doi.org/10.1038/s41598-023-38904-1 |
| spellingShingle | Lisette J. A. Kogelman Katrine Falkenberg Filip Ottosson Madeleine Ernst Francesco Russo Valdemar Stentoft-Hansen Samuel Demharter Peer Tfelt-Hansen Arieh S. Cohen Jes Olesen Thomas Folkmann Hansen Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms Scientific Reports |
| title | Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms |
| title_full | Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms |
| title_fullStr | Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms |
| title_full_unstemmed | Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms |
| title_short | Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms |
| title_sort | multi omic analyses of triptan treated migraine attacks gives insight into molecular mechanisms |
| url | https://doi.org/10.1038/s41598-023-38904-1 |
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