Project/Area Number |
15K12772
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Basic / Social brain science
|
Research Institution | National Institutes for Quantum and Radiological Science and Technology |
Principal Investigator |
Minamimoto Takafumi 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, チームリーダー(定常) (50506813)
|
Co-Investigator(Renkei-kenkyūsha) |
NAGAI Yuji 量子科学技術研究開発機構, 放射線医学総合研究所・脳機能イメージング研究部, 研究員 (20415409)
JI Bin 量子科学技術研究開発機構, 放射線医学総合研究所・脳機能イメージング研究部, 主任研究員 (80392223)
|
Research Collaborator |
KIKUCHI Erika
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | イメージング / PET / サル / 化学遺伝学 / 脳・神経 / 霊長類 / 遺伝子 |
Outline of Final Research Achievements |
This research aimed at establishing two technologies, in vivo monitoring of gene expression in the brain and noninvasive neural projection mapping technology. Using PET with 11C-clozapine, we succeeded in visualizing the inhibitory DREADD, hM4Di expressed in the putamen of monkeys. To improve the sensitivity of DREADD-PET imaging, we developed a new ligand, a carbon-11-labeled derivative of DREADD agonists. As seen with 11C-clozapine, PET imaging localized an increased uptake of the new ligand at the putative hM4Di-expressing site. Compared with 11C-clozapine, the signal-to-noise ratio was largely improved. Besides the injection site in the putamen, an increased uptake was also found in its projection areas, i.e., the globus pallidus and the substantia nigra, presumably reflecting hM4Di expression at the axon terminal. These results indicate that the new PET ligand provides a high DREADD selectivity, and thus enables noninvasive neural projection mapping.
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