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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）是一种独特的非侵入性脑化学检查方法，使用PET技术，可以测量活体人脑中特定的神经化学系统，如多巴胺能和组胺能神经系统。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踪剂。我们还开发了几种新的方法成像在人脑中使用三维PET系统。我们开发的用于人类神经药理学的PET方法如下：受体结合参数的无创测量; H_2^ O和3D-PET脑激活研究<15>; C-配体激活研究以测量神经递质释放。本课题主要研究人脑组胺能神经元系统的PET显像。抗组胺药是治疗过敏性疾病的有效药物。抗组胺药的安全性问题是至关重要的，因为它们具有预防作用。 ...更多信息 D在当前的医疗实践中使用。PET用于更好地了解抗组胺药对中枢神经系统的药理作用。年轻男性志愿者<11>口服或静脉注射抗组胺药后，用[^ C]-多塞平（一种有效的H1拮抗剂）检查H1受体结合率。在其他研究中，认知表现也在服用抗组胺药前后进行了速示检查。由抗组胺药引起的人类额叶皮层中的H1受体占用与临床试验中报告的嗜睡发生率值显著相关，并且占用与受损的认知表现成正比。为了解抗组胺药引起“嗜睡和认知障碍”的脑机制，应用3D-PET和H_2^ O测定了d-氯苯那敏（d-chlorpheniramine，d-氯苯那敏）治疗前后大鼠作业过程中局部脑血流量（rCBF）<15>的变化。给药后，双侧颞中回、中脑和扣带回前部的rCBF显著降低。这些发现表明，H1受体阻断剂会影响大脑中注意和认知系统的活动。少