Nishikawa M, Kumakura Y, Young S N, Fiset P, Vogelzangs N, Leyton M, Benkelfat C, Diksic M
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University St. Montreal, QC H3A2B4, Canada.
Neurochem Int. 2005 Dec;47(8):556-64. doi: 10.1016/j.neuint.2005.07.006. Epub 2005 Sep 12.
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.
本研究的主要目的是验证一个假设,即通过正电子发射断层扫描(PET)利用α-[(11)C]甲基-L-色氨酸(α-MTrp)捕获来测量的脑血清素(5-HT)合成,可因血氧变化而受到调节。该研究纳入了6名健康参与者(3名男性和3名女性),他们在注射示踪剂前15分钟开始呼吸15%或60%的氧气混合物,并在整个采集期间持续呼吸。参与者注射了高达12m Ci的α-MTrp。在参与者呼吸每种氧气混合物时采集了两组PET图像,重建后,所有图像都转换为显示脑捕获常数K*(微升/克/分钟)的脑功能图像。在磁共振图像上勾勒出12个感兴趣区域,并获得其K值。使用Tukey事后检验通过配对统计比较高血氧含量和低血氧含量下获得的K值。由于血浆色氨酸浓度没有差异,这些K值与区域5-HT合成直接相关。结果显示,相对于低血氧水平(平均值77.1±7.7 mmHg),高血氧水平(平均值223±41 mmHg)时脑血清素合成(K值)显著增加(平均增加50%)。这表明在活体人脑中色氨酸羟化酶并未被氧气饱和,血氧增加可提高脑血清素合成。