ROLE OF GLUTAMATE ACTIVATION IN ALZHEIMER'S

这项提议的目的是直接在小鼠的大脑中测试一种老年人 人们普遍认为，过量的钙通过 谷氨酸受体可导致神经退行性脑疾病 在阿尔茨海默氏症患者中观察到。这将通过遗传来实现 改造小鼠，使它们表达谷氨酸受体， 在正常突触过程中异常高的钙离子进入细胞 变速箱。 这些实验将利用重组DNA技术和 用基因工程方法培育突变小鼠。基因打靶 这些方法将被用来敲除或破坏谷氨酸受体基因。 点突变将被引入谷氨酸受体基因中 最近开发的“肇事逃逸”技术。 将使用各种技术对突变小鼠进行分析。这个 大脑将被切片并检查大体形态变化和 细胞死亡的证据。切片制备将用于测量 突触传递与突触经历突触的能力 LTP、LDP等塑性现象。将使用莫里斯迷宫 测试学习和记忆功能。

The aim of this proposal is to test directly in the mouse brain an old and widely believed idea that excess calcium entering a neuron through glutamate receptors can cause neurodegenerative brain disease as is observed in Alzheimer's patients. This will be accomplished by genetic engineering mice so that they express glutamate receptors which flux abnormally high amounts of calcium into the cell during normal synaptic transmission. The experiments will make use of recombinant DNA technology and the production of mutant mice by genetic engineering methods. Gene targeting methods will be used to knockout or disrupt glutamate receptor genes. Point mutations will be introduced into glutamate receptor genes using the recently developed "Hit and Run" technology. The mutant mice will be analyzed using a variety of techniques. The brains will be sectioned and examined for gross morphology changes and evidence of cell death. The slice preparation will be used to measure synaptic transmission and the ability of the synapses to undergo synaptic plasticity phenomenon such as LTP and LDP. The Morris maze will be used to test for learning and memory function.