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

对脑内胆碱能神经支配的核医学成像进行了基础性研究。用鹅膏酸损毁大鼠一侧基底脑，建立胆碱能去神经模型，是阿尔茨海纳病的动物模型之一。为了从获得新反应和长时间保持两个方面评价被动回避的表现，新研制了一种高精度的避暗装置。获得潜伏期在模型组和假对照组之间没有显著差异。然而，模型显示，与假对照组相比，保留潜伏期在统计学上显著缩短。组织化学检查发现，苍白球腹侧肾核、实质无名核和基底前脑损伤的内囊的神经细胞丢失、胶质增生和乙酰胆碱酯酶(AChE)染色减弱。此外，还观察到额叶、顶叶和颞叶…的AChE染色减少模型组病变同侧L投射皮质较多。顶叶皮质氯化乙酰转移酶(CAT)和乙酰胆碱酯酶(AChE)的定量测定显示，同侧较对侧分别平均下降46%和40%。这些结果表明，该动物模型被批准为阿尔茨海默病的合适实验模型。顶叶皮质乙酰胆碱的定量测定显示，患侧较对侧平均减少31%，差异有统计学意义。体外受体放射自显影显示病变同侧和对侧脑皮质M_1和M_2受体无显著差异。用~3H-2-(4-苯基哌啶基)环己醇(AH5183)同时切断突触前胆碱能神经，发现AH5183的平均结合量较对侧额顶叶-颞叶皮质减少14%。这些结果表明，AH5183是胆碱能神经支配的理想配基。鉴于AH5183在SPECT研究中的应用，有望获得AH5183的^&lt；123&gt；i或^&lt；99m；tc标签。较少

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