title: Increasing blood oxygen increases an index of 5-HT synthesis in human brain as measured using alpha-[(11)C]methyl-L-tryptophan and positron emission tomography.
abstract: The main objective of this investigation was to test the hypothesis that brain serotonin (5-HT) synthesis, as measured by trapping of alpha-[(11)C]methyl-L-tryptophan (alpha-MTrp) using positron emission tomography (PET), can be modulated by changes in blood oxygen. The study involved six healthy participants (three male and three female), who breathed a 15% or 60% oxygen mixture starting 15 min before the injection of tracer and continuing during the entire acquisition period. Participants were injected with up to 12m Ci of alpha-MTrp. Two sets of PET images were acquired while the participants were breathing each of the oxygen mixtures and, after reconstruction, all images were converted into brain functional images illustrating the brain trapping constant K(*) (microL/g/min). The K(*) values were obtained for 12 regions of interest outlined on the magnetic resonance images. The K(*) values obtained at high and low blood oxygen content were compared by paired statistics using Tukey's post hoc correction. As there were no difference in plasma tryptophan concentrations, these K(*) values are directly related to regional 5-HT synthesis. The results showed highly significant increases (50% on average) in brain serotonin synthesis (K(*) values) at high (mean value of 223+/-41 mmHg) relative to low (mean value 77.1+/-7.7 mmHg) blood oxygen levels. This suggests that tryptophan hydroxylase is not saturated with oxygen in the living human brain and that increases in blood oxygen can elevate brain serotonin synthesis.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University St. Montreal, QC H3A2B4, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kumakura
authors.forename: S N
authors.initials: SN
authors.lastname: Young
authors.forename: P
authors.initials: P
authors.lastname: Fiset
authors.forename: N
authors.initials: N
authors.lastname: Vogelzangs
authors.forename: M
authors.initials: M
authors.lastname: Leyton
authors.forename: C
authors.initials: C
authors.lastname: Benkelfat
authors.forename: M
authors.initials: M
authors.lastname: Diksic
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000502:physiology*; D049268:Positron-Emission Tomography; D012701:Serotonin / Q000096:biosynthesis*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D002250:Carbon Radioisotopes; C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan; D014365:Tryptophan Hydroxylase; D010100:Oxygen