Fundamental Study on Assessment of Neurotransplantation and Drug Treatment in Alzheimers Disease Using Nuclear Medicine Imaging

(1)本研究将β-淀粉样蛋白注入大鼠脑室14 d；采用八臂放射状迷宫评价记忆能力。在同一动物中，测定囊泡乙酰胆碱转运体和毒蕈碱乙酰胆碱受体密度。β-淀粉样蛋白处理大鼠的八臂径向迷宫任务表现受损。在新皮层中，β-淀粉样蛋白处理的大鼠囊状乙酰胆碱转运体密度低于对照品处理的大鼠；两组毒蕈碱乙酰胆碱受体密度无差异。这些结果表明，囊泡乙酰胆碱转运体密度的降低与β-淀粉样蛋白诱导的记忆损伤有关。(2)认为结节神经节移植可改善大细胞基底核损伤大鼠的学习记忆障碍，[^3H]-维萨米醇是突触前胆碱能神经元的作图剂之一。采用高灵敏度显像板系统进行定量放射自显像，评价神经移植对[^3H]-维萨米醇结合的影响。大细胞基底核病变组[^3H]-维萨米醇在1、2、4周时的患侧与未患侧比值显著低于假手术组（p< 0.01）。移植组在4周时的比例显著高于未治疗组（p<0.05）。[^3H]-vesamicol结合是大细胞基底核病变及结节神经节移植效果最敏感的指标之一。

(1) In this study, β-amyloid protein was infused into the cerebral ventricle of rats for 14 days ; the eight-arm radial maze was used to evaluate memorial ability. In the same animals, vesicular acetylcholine transporter and muscarinic acetylcholine receptor density was measured. The performance of the eight-arm radial maze task was impaired in β-amyloid protein treated rats. In neocortex, the vesicular acetylcholine transporter density was lower in β-amyloid protein-treated rats than vehicle treated rats ; there was no difference in muscarinic acetylcholine receptor density between the two groups. These results suggest that the reduction in vesicular acetylcholine transporter density is related to memory impairment induced by β-amyloid protein.(2) It is considered that the nodosal ganglion grafting improves the learning and memory disorder in the nucleus basalis magnocellularis lesioned rat, and that [^3H]-vesamicol is one of the mapping agents for presynaptic cholinergic neurons. Quantitative autoradiography was performed using high sensitive imaging plate system to evaluate the effect of neurotransplantation on [^3H]-vesamicol binding. The affected-side to unaffected-side ratio of [^3H]-vesamicol in the nucleus basalis magnocellularis lesioned group was significantly lower than that in the sham-operated group at I , 2 and 4 weeks (p< 0.01). In the transplanted group, the ratio was significantly higher than that in the untreated group at 4 weeks (p<0.05). [^3H]-vesamicol binding is one of the most sensitive indicators of nucleus basalis magnocellularis lesions and the effect of the nodosal ganglion grafting.