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

利用核医学成像评估阿尔茨海默病神经移植和药物治疗的基础研究

• 批准号: 10670832
• 负责人: MORI Hirofumi
• 金额: $ 1.92万
• 依托单位: KANAZAWA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670832/
• 关键词: Alzheimer's disease; Lesion of Nucleus Basalis Magnocellularis; Acetylcholine; Receptor; Neurotransplantation; Transporter; β-amyloid

(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.

(1)本研究将β-淀粉样蛋白（β-amyloid protein，AP）注入大鼠脑室，连续14 d，采用八臂迷宫法检测大鼠的记忆能力。在相同的动物，囊泡乙酰胆碱转运蛋白和毒蕈碱乙酰胆碱受体密度进行了测量。β-淀粉样蛋白处理的大鼠八臂径向迷宫任务的表现受损。在新皮质中，β-淀粉样蛋白给药大鼠的囊泡乙酰胆碱转运蛋白密度低于溶剂给药大鼠;两组之间的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障碍有关。(2)认为结状神经节移植可改善基底核大细胞毁损大鼠的学习记忆障碍，[^3H]-维索霉素是突触前胆碱能神经元的定位剂之一。采用高灵敏度成像板系统进行定量放射自显影，以评价神经移植对[^3H]-vesamicol结合的影响。大细胞基底核毁损组大鼠的[^3H]-vesamicol患侧/健侧比值在第1、2、4周均显著低于假手术组（p< 0.01）。移植组4周时，其比值明显高于未治疗组（p<0.05）。[^3H]-vesamicol结合是基底核大细胞病变和结状神经节移植效果的最敏感指标之一。

项目成果

Ikeda E: "Reduction of vesicular acetylcholine transporter in β-amyloid protein-infused Rats with memory impairment"Nuclear Medicine Communications. 21. 933-937 (2000)

Ikeda E：“记忆障碍的 β-淀粉样蛋白注入大鼠中囊泡乙酰胆碱转运蛋白的减少”核医学通讯 21. 933-937 (2000)。

Shiba K: "The potential of radioiodinated(-)-m-iodovesamikol for diagnosing cholinergic deficit dementia"Nuclear Medicine & Biology. (in press).

Shiba K：“放射性碘化 (-)-m-iodovesamikol 诊断胆碱能缺陷性痴呆的潜力”核医学

Ikeda E: "Effect of vagal autotransplantation on quantitative [^3H] -vesamicol bindingimage in rats with unilateral lesions of nucleus basalis magnocellularis"Neuroscience Letters. (in press).

Ikeda E：“迷走神经自体移植对大细胞核基底核单侧损伤大鼠定量 [^3H]-vesamicol 结合图像的影响”神经科学快报。

Ikeda E: "Effect of vagal autotransplantation on quantitative [^3H]-vesamicol bindingimage in rats with unilateral lesions of nucleus basalis binding image"Neuroscience Letters. (in press).

Ikeda E：“迷走神经自体移植对单侧基底核损伤大鼠定量 [^3H]-vesamicol 结合图像的影响”神经科学快报。