| Project/Area Number |
63440040
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Radiation science
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| Research Institution | Kanazawa University |
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Principal Investigator |
HISADA Kinichi Kanazawa University, School of medicine, Professor, 医学部, 教授 (50019882)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Hiroshi Kanazawa University, School of Medicine, Assistant, 医学部, 助手 (90173848)
SHIBA Kazuhiro Kanazawa University, Radioisotope Center, Assistant, アイソトープ総合センター, 助手 (40143929)
AMANO Ryohei Kanazawa University, School of Allied Medical Professions, Associate professor, 医療技術短期大学部, 助教授 (30111769)
MORI Hirofumi Kanazawa University, Radioisotope Center, Associate Professor, アイソトープ総合センター, 助教授 (90019604)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1989: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1988: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | dementia / neurotransmitter / autoradlography / neuroreceptor / acetylcholine / radioligand / nuclear medicine imaging / Alzheimers disease / アルツハイマー型痴呆 / ラットモデル / アセチルコリンエステラーゼ / 受動的回避運動 / 受容体 / オートラジオグラフィ / QNB |
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| Research Abstract |
A fundamental study was performed on the nuclear medicine imaging of cholinertic innervation in the brain. A cholinergic denervation model was experimentally prepared by producing an ibotenic acid lesion in unilateral basaltorebrain in the rat, which is reported to be one of animal models of Alzheiner's disease. To assess the passive avoidance performance in terms of acquisition of new responses and long tern retention, a step-through apparatuswith high precision was newly developed. Acquisition latencies showed no significant differences between models and sham-controls. However, models revealed statistically significant shorter retention latencies than sham-controls. Histochemical investigation disclosed neuronal cell loss, gliosis, and diminished acetylcholine esterase (AchE) staining in a ventral renon of globus pallidus, substantial innominata, and internal capsule in the basal forebrain lesion. Furthermore decreased AchE staining was observed in the frontal, parietal, and tempora
… More
l projection cortices ipsilateral to the lesion in models. Quantitative determination of chorine acetyltransferase (CAT) and AchE in parietal cortices showed statistically significant 46% and 40% decrease on an average, respectively,in the ipsilateral side compared to the contralateral side. These results suggest that this animal model is approved as an appropriate experimental model of Alzheimer's disease. Quantitative determination of acetylcholine in parietal cortices revealed statisticallysigniticant 31% decrease on an average in the ipsilateral side relative to the contralateral side to the lesion. In-vitro receptor autoradlography showed no significant differences in total, M_1, and M_2 muscarinic acetylcholine receptors between the ipsllateral and contralateral cortices to the lesion. Simultaneous sapping of presynaptic cholinertic innervation using ^3H-2-(4-phenylpiperidino)cyclohexanol (AH5183) demonstrated sitniticant 14% decrease of AH5183 bindint on an averate in the ipsilateral relative to the contralateral fronto-parieto-temporal cortices to the lesion. These results suggest that AH5183 is a promissint ligand for tapping cholinersic innervation. The ^<123>I or ^<99m>Tc labelling of AH5183 is to be expected in view of application to a SPECT study. Less
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