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Animal models having deficiency in leatning and memory

学习和记忆缺陷动物模型

基本信息

批准号：
61870107
负责人：
YOSHIDA Hitoshi
金额：
$ 6.91万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

Our project is to make animal models having deficency in learning and memory, especially in relation with Alzheimer's desease. In Alzheimer's patients it is generally known that there is degenration in Meynert nucleus which contains chelinergic neurons innervationg the frontal and parietal cortices. Standing on these considetations we carried experimaents and following resuls were obtained.I) Injection of prBMC (proplybenzilylcholine mustard), irrversible antagonist of muscatinic acetylcholine receptor, into rat brain frontal and parietal cortices caused dificit in passive avoidance learning. But its injection into the occipital cortex did not cause significant deficit. Furthermore we examine the effect of prBCM on three phases of the memory, acquisition, retention and recalling phase. By out results, acquisition and recalling phases were impaired by prBCM byt retention phase was not significantly influenced by the injection.II) In shuttle active aboicdance leatning we also observed a deficient by injection of PrBCM iinto fronatl and parieral cortices of the rat. These results indicate that impairment in cholinergin synapses caused deficits in leatning and memory process.III) In search for endfogenous substances which cause degeneration of cholinergic neurons, we found taht injection of quinolinic acid, a metablit tryptophan, into basal nucleus to Meynert caused degenetation of cholinergic neuron in rat brain cortex by estimation of CAT (choline acetyl transterase) activity. Behavioral study on learning- and memory on these quinolinatetrasted rats progressed in our laboratory new. In the other hand we found that quainolinic acid have high affinity on gultamate receprots by binding experiments with^3H-gultamate of^3H-CPP (3-(2-carboxypiperazin-4yl)-propyl-phosphoric acid). This quinolinic acid-trated rats maybe one type of deficit model animal on learning and memory.

我们的项目是制作学习记忆障碍的动物模型，特别是与阿尔茨海默病有关的动物模型。阿尔茨海默病患者的Meynert核变性是众所周知的，Meynert核含有支配额叶和顶叶皮质的胆碱能神经元。基于上述考虑，我们进行了以下实验，结果表明：（1）向大鼠大脑额叶和顶叶皮质注射M胆碱能受体拮抗剂prBMC（prostaglandin benzilylcholine mustard，probenzilylcholine mustard），可引起被动回避学习障碍。但其注射到枕叶皮质并没有造成明显的缺陷。此外，我们还研究了记忆的三个阶段，即获得阶段、保持阶段和回忆阶段。结果表明，注射PrA后，大鼠的记忆和获得相均受到抑制，而记忆保持相则不受注射PrA的影响。这些结果表明，胆碱能神经元突触损伤可引起学习记忆过程的障碍。（3）在寻找引起胆碱能神经元变性的内源性物质时，我们用胆碱乙酰转移酶（CAT）测定发现，将色氨酸的代谢产物喹啉酸注入Meynert基底核，可引起大鼠大脑皮层胆碱能神经元变性。本实验室对喹啉类药物致大鼠学习记忆障碍的行为学研究取得了新的进展.另一方面，通过与3-（2-羧基哌嗪-4基）丙基磷酸（3-（2-carboxypiperazin-4 yl）-propyl-phosphate，CPP）的3-H-谷氨酸受体的结合实验，发现喹喔啉酸对谷氨酸受体有很高的亲和力。喹啉酸中毒大鼠可能是一种学习记忆障碍模型动物。