2004 Fiscal Year Final Research Report Summary
The evaluation of nicotinic acetylcholine receptors in patients with neurodegenerative disorders
| Project/Area Number |
14370205
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kyoto University |
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Principal Investigator |
FUKUYAMA Hidenao Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (90181297)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIKAWA Kazuo Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (70281128)
SAJI Hideo Kyoto University, Graduate School of Pharcology, Professor, 医学研究科, 教授 (40115853)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Nicotinic receptor / neurodegenerative disorder / smoking / SPECT |
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| Research Abstract |
Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in the human brain. Recently, 5-iodo-3-(2S)-azetidinylmethoxy) pyridine (5IA) has been synthesized as a radioligand for imaging nAChRs with SPECT. The purpose of this study was to establish the quantitative measurements of nAChR binding by using 5IA SPECT and apply it to neurodegenerative disorders.
In the healthy volunteers, a 6-h dynamic SPECT acquisition was performed just after an I-123 5IA injection. Arterial blood samplings were done and pure 5IA concentrations were obtained by the TLC as input function. Two-compartment model (2C) and Logan plot were applied for kinetic analysis. Two scans were done in the smoking healthy volunteers, one was under smoking state and another was after 20-days smoke-free period. We also performed 5IA SPECT studies in the patients with Alzheimer's disease (AD) and Parkinson's disease (PD).
Good relationship was found between two distribution volumes(DV) obtained by using 2C and Logan plot. DVs were the highest in the thalamus, moderate in the pons, cerebellum, basal ganglia, lower in cerebral cortices. Good agreement was observed between DV values and results of autoradiographic experiments done in vitro for nAChR density in human brain. The DV during smoking were significantly lower than those under smoke-free state. The DV values of AD were significantly reduced in all brain regions in comparison with those of normal controls. The DVs of PD were significantly lowered in the thalamus and the pons. The significant reductions were found in DVs of akinesia dominant PD patients in almost all brain regions, however, only in the thalamus in DVs of tremor dominant patients, which may be related with the efficacy of anti-cholinergic drugs for symptoms of PD.
Our results indicated that 5IA SPECT may become a useful method for the quantitative measurements for nAChRs in neurodegenerative disorders.
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Research Products
(19 results)
