Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms
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Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms. / Kogelman, Lisette J.A.; Falkenberg, Katrine; Ottosson, Filip; Ernst, Madeleine; Russo, Francesco; Stentoft-Hansen, Valdemar; Demharter, Samuel; Tfelt-Hansen, Peer; Cohen, Arieh S.; Olesen, Jes; Hansen, Thomas Folkmann.
In: Scientific Reports, Vol. 13, 12395, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms
AU - Kogelman, Lisette J.A.
AU - Falkenberg, Katrine
AU - Ottosson, Filip
AU - Ernst, Madeleine
AU - Russo, Francesco
AU - Stentoft-Hansen, Valdemar
AU - Demharter, Samuel
AU - Tfelt-Hansen, Peer
AU - Cohen, Arieh S.
AU - Olesen, Jes
AU - Hansen, Thomas Folkmann
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-023-38904-1
DO - 10.1038/s41598-023-38904-1
M3 - Journal article
C2 - 37524744
AN - SCOPUS:85166083500
VL - 13
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 12395
ER -
ID: 361847817