1994 Fiscal Year Final Research Report Summary
Turnover of neurotransmitters in the living and functional brain analized by positron emission Tomography
| Project/Area Number |
04044182
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
WATANABE Yasuyoshi Head, Department of Neuroscience, Osaka Bioscience Institute, 第3研究部, 研究部長 (40144399)
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| Co-Investigator(Kenkyū-buntansha) |
ONOE Hirotaka Research Scientist, Department of Neuroscience. Osaka Bioscience Institute, 第3研究部, 研究員 (80214196)
MIWA Souichi Vice-professor, Department of Medicine, Kyoto University, 医学部, 助教授 (40157706)
INOUE Osamu Head, Division of Clinical Research and Radiation Health, National Radiological, 障害臨床研究部, 室長 (50159969)
LANGSTROM Bengt Director, Uppsala University, PET Center, PETセンター 兼 化学研究所, 所長教授
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| Project Period (FY) |
1992 – 1994
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| Keywords | Positron emission tomography / Dopaminergic system / Dopamine turnover / Dopamine D_2 receptor / Glutamate system / Infantile antism / Schizophrenia / Brain ischemia model |
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| Research Abstract |
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.
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