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Basic research on neurotransmitter mapping for establishing objective nuclear medicine imaging of dlementia

建立痴呆客观核医学成像的神经递质图谱基础研究

基本信息

批准号：
63440040
负责人：
HISADA Kinichi
金额：
$ 5.06万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

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

对大脑胆碱神经支配的核医学成像进行了基础研究。通过在大鼠单侧基底脑中产生鹅膏菌酸损伤，实验性地制备了胆碱能去神经模型，据报道这是阿尔茨海纳病的动物模型之一。为了评估被动回避在获得新反应和长期保留方面的表现，新开发了一种高精度的步进装置。模型和假对照组之间的采集潜伏期没有显着差异。然而，模型显示统计上的保留潜伏期比假对照组显着缩短。组织化学研究揭示了基底前脑病变中苍白球腹侧肾脏、实质无名体和内囊的神经元细胞损失、神经胶质增生和乙酰胆碱酯酶 (AchE) 染色减少。此外，在模型中病变同侧的额叶、顶叶和颞叶投射皮质中观察到 AchE 染色减少。顶叶皮质中氯乙酰转移酶（CAT）和 AchE 的定量测定显示，与对侧相比，同侧平均分别降低了 46% 和 40%，具有统计学意义。这些结果表明该动物模型被批准作为阿尔茨海默病的合适实验模型。顶叶皮质中乙酰胆碱的定量测定显示，相对于病变的对侧，同侧的乙酰胆碱平均减少了 31%，具有统计学意义。体外受体放射自显影显示病变同侧和对侧皮质之间的总毒蕈碱乙酰胆碱受体、M_1 和 M_2 没有显着差异。使用 ^3H-2-(4-苯基哌啶基)环己醇 (AH5183) 同时削弱突触前胆碱神经支配表明，相对于病变的对侧额顶颞叶皮质，AH5183 的平均结合力降低了 14%。这些结果表明 AH5183 是利用胆碱神经支配的前配体。鉴于应用于SPECT研究，AH5183的^ 123 I或^ 99m Tc标记是预期的。较少的