Pharmacological studies on animal models of Alzheimer disease and Senile dementia, and development of therapeutic drugs

阿尔茨海默病和老年痴呆动物模型的药理研究及治疗药物的开发

• 批准号: 62570979
• 负责人: WATANABE Hiroshi
• 金额: $ 1.28万
• 依托单位: Toyama Medical and Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570979/
• 关键词: animal model; Alzheimer disease; Senile dementia; vincristine; ドーパミン; アセチルコリン; アルツハイマー病; 病態モデル

1. Animal models of alzheimer disease and senile dementia, and behavioral changes(1) In rats treated with vincristine into the nuilateral striatum, apomorphine produced transient rotational behavior 2 to 3 days agter the treatment.(2) Microinjection of vincristine into the bilateral striata prevented the acquisition and retention of spatial memory of rats 3 to 5 days after the injection. Since these rats died due to the paralysis of four legs by two to four weeks after the injection, vincristine-induced lesion was considered to be progressive.2. Changes of neurotransmitters in the striatum of the model animals(1) Measurement of catecholamines: Striatal dopamine and its metabolites slightly decreased 7 to 8 days after the intrastriatal microinjection of vincristine.(2) receptor binding assay: [^3H]-spiperone binding to striatal membranes decreased after vincristine treatment. Further investigation is required to clarify if an animal model of alzheimer disease is sensitive to drugs.

1.阿尔茨海默病和老年性痴呆动物模型及行为学改变（1）长春新碱注入大鼠侧纹状体后，阿朴吗啡在2 ~ 3天后可引起短暂的旋转行为。(2)双侧纹状体微量注射长春新碱3 ~ 5d后，大鼠空间记忆的获得和保持均受到抑制。由于这些大鼠在注射后2 - 4周因四肢瘫痪而死亡，长春新碱诱导的病变被认为是进行性的。模型动物纹状体神经递质的变化（1）儿茶酚胺测定：纹状体内微量注射长春新碱后7 ~ 8天，纹状体多巴胺及其代谢产物轻度降低。(2)受体结合试验：长春新碱处理后，[^3H]-螺哌隆与纹状体膜的结合减少。需要进一步的研究来澄清阿尔茨海默病的动物模型是否对药物敏感。

项目成果

渡辺裕司: 日本薬理学雑誌. 94. (1989)

渡边雄二：日本药理学杂志 94。（1989）

Hiroshi Watanabe: "Effect of vincristine on spatial memory of rats" Folia pharmacol. japon.

Hiroshi Watanabe：“长春新碱对大鼠空间记忆的影响”Foliapharmacol。