PhD defence: Marie Deen
- Published: Monday, 17 December 2018 14:07
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The defence will take place in Auditorium C, Rigshospitalet Glostrup, Valdemar Hansens Vej 5, 2600 Glostrup.
Chairperson: Professor Steen Gregers Hasselbalch, University of Copenhagen
Opponent: Professor Andrew Charles, UCLA, Los Angeles
Opponent: Associate Professor Andrea Varrone, Karolinska Institute, Stockholm
Principal supervisor: Professor Messoud Ashina, University of Copenhagen
Primary co-supervisor: Professor Gitte Moos Knudsen, University of Copenhagen
Co-supervisor: Anders Hougaard, MD, PhD, Rigshospitalet
Co-supervisor: Hanne Demant Hansen, PhD, Rigshospitalet
Migraine is the most prevalent and disabling neurological disorder worldwide. Since the 1960s serotonin (5-HT) has been implicated in migraine pathophysiology but the exact role of brain serotonin levels in migraine is still unknown. The overall goal of the thesis was to investigate the serotonergic system in the migraine brain using positron emission tomography imaging of two different serotonin receptors.
We used 5-HT4 receptor binding as a biomarker of brain serotonin levels. Based on the serotonin deficiency theory in migraine, we hypothesized that migraine patients would have higher 5-HT4 receptor binding compared to controls. Instead, we found that patients had lower 5-HT4 receptor binding indicating higher brain serotonin levels. However, there was no difference between chronic and episodic migraine patients. This suggests that a high level of brain serotonin is an inherent trait of the migraine brain.
We also investigated 5-HT1B receptor binding in episodic migraine patients and found that they had lower 5-HT1B receptor binding across pain-modulating brain regions compared to controls. During migraine attacks we found that the 5-HT1B receptor binding was reduced compared to outside of attacks, indicating that brain serotonin levels increase during attacks. After treatment with sumatriptan, the 5-HT1B receptor binding decreased further, indicating that sumatriptan binds to central 5-HT1B receptors.
In conclusion, the present thesis supports the hypothesis that the serotonergic system plays a role in migraine pathophysiology, with migraine patients exhibiting high brain serotonin levels between attacks, which increase further during attacks. Further, we show that the 5-HT1B receptor density is altered in migraine patients and provide evidence that sumatriptan may act on central 5-HT1B receptors.