Summary of Research Project Results under JSPS FY2001
"Research for the Future Program"

1.Research Institution Osaka City University
2.Research Area Life Sciences
3.Research Field Higher Brain Functions
4.Term of Project FY 1998 〜 FY 2001
5.Project Number 98L00201
6.Title of Project Molecular Dynamics Imaging by Use of PET

7.Project Leader
Name Institution,Department Title of Position
Yasuyoshi, Watanabe Osaka City University, Graduate School of Medicine Professor

8.Core Members

Names Institution,Department Title of Position
Kazuyuki, Imamura Osaka Bioscience Institute, Dept. Neuroscience Vice-Head
Kiyoshi, Matsumura Kyoto University, Graduate School of Informatics Associate Professor
Yosuke, Kataoka Osaka Bioscience Institute, Dept. Neuroscience Research Scientist

9.Summary of Research Results

We aimed to explore the molecular dynamics in highly functioning brain and intended to develop the molecular probes for that purpose by use of Positron Emission Tomography (PET). For the basis, we also have to unveil the brain regions or circuits responsible for such higher brain function.
(1) By PET activation studies, we unveiled the neural substrates, i. e., the brain regions responsible for higher brain functions, such as visual recognition, time perception, and learning set formation in monkeys, and laughter or smile, and metal fatigue in human volunteers. Top-down signals of smell and taste have been studied with functional MRI in human volunteers.
(2) We developed a new method for controlling local brain activities to assess the activation sites or circuits obtained by the activation study using neuroimaging techniques such as PET and fMRI. Two unique methods were developed; Photo-Dynamic Tissue Oxidation (PDTO), and a laser light irradiation into the brain tissue. Both methods were able to be applied to suppress the neuronal activity in behaving animals.
(3) We developed novel molecular probes for PET; mostly, glutamate receptor system, prostaglandin receptor, and nicotinic and muscarinic cholinergic receptor systems. PET studies were performed with these ligands, in normal volunteers and patients.
(4) We also developed the radiotracers for PET to seek for brain-specific metabolism such as lactate and acetyl-L-carnitine, and demonstrated the brain-specific role of these molecules, related to the neural function.
(5) For the imaging of gene expression, we developed the key radiotracers for labeling oligonucleotides. By using radiolabelled oligonucleotides, we showed the radiolabel when injected into rats is mostly incorporated into DNA/RNA fraction and protein binding. MicroPET was introduced for PET imaging of smaller animals for this purpose. The performance by MicroPET has been established in our group.

10.Key Words

(1)Higher Brain Function、(2)Neuroimaging、(3)Positron Emission Tomography (PET)
(4)Molecular Dynamics、(5)Activation study、(6)Development of Molecular Probes
(7)Prostaglandin Receptor、(8)Gene Expression Imaging、(9)Transition of Active Brain Regions