Neurotransmission in human brains measured by 3D-PET

通过 3D-PET 测量人脑的神经传递

基本信息

批准号：
08044235
负责人：
YANAI Kazuhiko
金额：
$ 8.38万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

Positron emission tomography (PET) is a unique method to examine brain chemistry non-invasively in humans.Using PET techniques, specific neurochemical systems, such as dopaminergic and histaminergic neuronal systems, was measured in the living human brain. For HA receptors, specific radiotracers for selective labeling of H3 receptors was newly synthesized. We also developed several new methods of imaging in the human brain using 3-demensional PET system. Our developed PET methods for human neuropharmacology are as follows : Non-invasive measurement of receptor binding parameters ; cerebral activation study with H_2^<15>O and 3D-PET ; "C-ligand activation study to measute neurotransmitter release. In this project, we were mainly focus on the PET studies of histaminergic neuron system in the human brain.Antihistamines are the efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamines is of central importance because of their widesprea … More d use in current medical practice. PET was used to better understand the pharmacological effects of antihistamines on the central nervous system. The H1 receptor occupancy was examined in young male volunteers with [^<11>C]-doxepin (a potent H1 antagonist) after the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The H1 receptor occupancy in the human frontal cortex caused by antihistamines is significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is well proportional to the impaired cognitive performance. To understand the brain mechanism of antihistamine-induced "sleepiness and impaired cognition", the regional cerebral blood flow (rCBF) during the task was measured using 3D-PET and H_2^<15>O before and after administration of d-chlorpheniramine. After its administration, the rCBF was significantly decreased on the bilateral middle temporal gyrus, midbrain and anterior cingulate. These findings suggest that H1 receptor blockade would be affected on the activity of the attention and cognitive system in the brain. Less

正电子发射断层扫描（PET）是一种独特的方法，可在人类中使用PET技术，在人类中进行非侵入性检查。对于HA受体，新合成了用于选择性标记H3受体的特异性放射性示意剂。我们还使用三维宠物系统开发了几种在人脑中成像的新方法。我们开发的人类神经药理学的PET方法如下：受体结合参数的非侵入性测量； H_2^<15> O和3D-PET的脑激活研究； “ C-LIGAND激活研究以测量神经递质释放。在该项目中，我们主要集中于人脑中组胺能神经系统的PET研究。抗组织胺是有效的药物用于症状性疾病，用于过敏性疾病的疾病。对抗组织症的安全性是较中心的，因为它们的较中心是更高的，因为它的范围更具范围的使用。抗组胺药对中枢神经系统的药物效果。抗组胺药与报道的临床试验中嗜睡发生率值显着相关，并且该占用率与认知性能受损成正比。为了了解抗组胺药诱导的“嗜睡和认知受损”的大脑机制，使用3D-PET和H_2^<15> O测量了在d-氯苯胺之前和之后测量任务过程中大脑血流（RCBF）。给药后，在双侧中部回，中脑和前扣带回上，RCBF显着降低。这些发现表明，H1受体阻滞将受到大脑注意力和认知系统的活性的影响。较少的