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Turnover of neurotransmitters in the living and functional brain analized by positron emission Tomography

通过正电子发射断层扫描分析活体和功能性大脑中神经递质的周转

基本信息

批准号：
04044182
负责人：
WATANABE Yasuyoshi
金额：
$ 20.48万
依托单位：
Osaka Bioscience Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

1) For functional imaging and quantifying glutamate NMDA-type receptor, [3-^<11>C-cyano]MK-801 has been developed. Prior to PET study, affinity and specificity of this newly synthesized ^<11>C-labelled compound were tested, and it gave a quite reasonable result. Then, PET study using this [3-^<11>C-cyano]MK- 801 was pesformed in an ischemic model of rhesus monkey brain. Compared with regional cerebral blood flow (rCBF) measured by use of ^<15>O-labelled water in PET,higher uptake of radioactivity derived from [3-^<11>C-cyano]MK-801 was obtained in the ischemic site of the brain, indicating comparably high glutamate release in this site. Usefulness of [3-^<11>C-cyano]MK- 801 has thus been assessed.2) Two more cases of autistic patients were treated with tetrahydrobiopterin (R-BH_4) for 12 weeks. Before and after the treatment, PET studies were carried out for regional cerebral blood flow (rCBF) , dopamine turnover, and dopamine D_2 receptor binding, using H_2^<15>O,L-^<11>C-DOPA,and N-^<11>C- methylspiperone, respectively. No significant abnormality of rCBF was observed. Dopamine turnover and dopamine D_2 receptor binding were extraordinarily high, and high value of receptor binding was decreased with improvement of clinical symptoms by treatment.3) In drug-naive schizophrenic patients, dopamine turnover rate measured by PET with L-^<11>C-DOPA was tremendously high, and this rate was decreased by clozapine treatment.4) To assess interactions among dopaminergic, acetylcholinergic, glutamatergic, and GABAergic systems in the brain, especially in the depression, Alzheimer's disease and other disorders mentioned above, we started the series of PET studies using hemilesioned monkeys in the dopaminergic pathway.

1)为了进行谷氨酸NMDA型受体的功能成像和定量，我们研制了[3-^&lt；11&gt；C-氰基]MK-801。在进行PET研究之前，对这个新合成的~&lt；11&gt；C标记化合物的亲和力和特异性进行了测试，得出了相当合理的结果。然后，在恒河猴脑缺血模型上进行了使用该[3-^&lt；11&gt；C-氰基]MK-801的PET研究。与用~(15)O标记的水在PET中测得的局部脑血流量(RCBF)相比，[3-~^&lt；11&gt；C-氰基]MK-801在脑缺血部位获得了更高的放射性摄取，表明该部位谷氨酸的释放相对较高。因此，[3-^&lt；11&gt；C-氰基]MK-801的有效性已被评估。2)又有两例自闭症患者接受了四氢生物蝶呤(R-BH_4)治疗12周。治疗前后分别用H_2&lt；15&gt；O、L-11&gt；C-多巴和N-甲基螺环酮测定局部脑血流量、多巴胺转换率和多巴胺D_2受体结合率。RCBF未见明显异常。3)在药物未用药的精神分裂症患者中，L-^&lt；11&gt；C-DOPA的正电子发射计算机断层扫描测得的多巴胺周转率非常高，而氯氮平治疗后这一比率降低。4)为了了解多巴胺能、乙酰胆碱、谷氨酸和GABA能系统在大脑中的相互作用，特别是在抑郁症、阿尔茨海默病和上述疾病中，我们开始了一系列的PET研究，使用偏侧的猴子在多巴胺能通路中。