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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）是一种独特的方法来检查大脑化学在人类的非侵入性。利用PET技术，在活人大脑中测量了特定的神经化学系统，如多巴胺能和组胺能神经元系统。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，利用三维PET系统在人脑成像。我们开发的用于人类神经药理学的PET方法有：无创测量受体结合参数；H_2^<15>和3D-PET脑活化研究c配体激活研究测量神经递质释放。在这个项目中，我们主要关注的是人脑组胺能神经元系统的PET研究。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，因为它们在当前的医疗实践中广泛使用。PET用于更好地了解抗组胺药对中枢神经系统的药理作用。在口服或静脉注射抗组胺药后，用[^< 11b> C]-多虑平（一种强效H1拮抗剂）检测年轻男性志愿者的H1受体占用情况。在其他研究中，在服用抗组胺药之前和之后，也用速视镜测量了认知表现。抗组胺药引起的H1受体在人额叶皮层的占据与临床试验中报道的嗜睡发生率显著相关，并且占据与认知能力受损成正比。为了解抗组胺诱导的“嗜睡和认知障碍”的脑机制，采用3D-PET和H_2^<15>测量d-氯苯那敏给药前后的脑血流（rCBF）。给药后，双侧颞中回、中脑和前扣带的rCBF明显减少。这些发现表明，H1受体阻断会影响大脑注意力和认知系统的活动。少