BASIC MECHANISMS OF HUMAN EPILEPSY

人类癫痫的基本机制

• 批准号: 3099895
• 负责人: ANTONIO V. DELGADO-ESCUETA
• 金额: $ 89.69万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3099895
• 关键词: epilepsy; immunocytochemistry; membrane channels; neurochemistry

This multidepartment, multi-instituite investigative effort on the basic mechanisms of human epilepsies evolved from the UCLA Comprehensive Epilepsy Program. It consists of nine component projects which examine the multifactorial mechanisms of temporal lobe epilepsies and the genetic mechanisms of benign juvenile myoclonic epilepsy. The first three projects examine the ion transport pathways of synaptic terminals and glial cells in lobectomy specimens of human temporal lobe epilepsies. (Na+K+)-ATPase, (Ca2+)-ATPase and ecto-ATPase activities are correlated in synapses and glial cells. The role of phosphorylation of brain membrane proteins with molecular weights of 18 K, 50-60 K, and 80 K in membrane permeability and depolarization is also studied in the lobectomy specimens. Biochemical and transport mechanisms of GABA and glutamate are further examined in synaptic terminals and glial cells. Ionic channels coupled to the GABA receptor are dissected in Project 4 by patch clamp recordings of single channel currents in dissociated cell cultures of hippocampus excised from lobectomy specimens. Project 5 assesses post-synaptic mechanisms of GABA actions; receptor binding sites for GABA and benzodiazepines are quantitated in homogenates of temporal lobectomy specimens. To provide a functional and morphological picture of neurons that use GABA or acetylcholine as neuroactive subsstances, the organization of GABA and Ach neurons in amygdala of anterior temporal lobectomy specimens are visualized by immunocytochemistry in Project 6. Animal experiments examine acquired and genetic epilepsies in Projects 1 to 6 and provide directions of research thrusts and new testable hypotheses for human temporal lobe epilepsies and juvenile myoclonic epilepsy. Projects 7 and 8 seek the chromosomal locus of juvenile myoclonic epilepsy by linkage analysis with 31 phenotypic blood markers and 20 restriction fragment length polymorphisms. Project 9 is developing candidate gene markers for human epilepsies and plans to engineer new genetic models of epilepsy by blocking the expression of genes for glutamic acid decarboxylase or GABA receptors. Through these nine mutually reinforcing component projects, new insights into the molecular mechanisms of acquired biochemical lesions and the epilepsy susceptibility gene of human epilepsies will be acquired.

这项多阶段，多机构的调查工作 人类癫痫的机制从UCLA综合癫痫演变而来 程序。 它由九个组件项目组成，这些项目检查 颞叶癫痫和遗传的多因素机制 良性青少年肌癫痫的机制。 前三个项目 检查突触末端和神经胶质细胞的离子传输途径 人颞叶癫痫的叶切除术标本。 （Na+K+） - ATPase， （Ca2+） - ATPase和Ecto-ATPase活性在突触中相关 神经胶质细胞。 脑膜蛋白磷酸化的作用 膜渗透性中的18 K，50-60 K和80 K的分子量和80 K 还研究了在小叶切除术标本中的去极化。 生化和 在突触中进一步检查了GABA和谷氨酸的运输机制 末端和神经胶质细胞。 与GABA受体耦合的离子通道是 单个通道电流的贴片夹记录在项目4中解剖 从叶切除术切除的海马的分离细胞培养物中 标本。 项目5评估GABA作用的突触后机制； GABA和苯二氮卓类药物的受体结合位点在 颞叶切除术标本的匀浆。 提供功能和 使用GABA或乙酰胆碱作为神经元的形态学图片 神经活性子阶层，GABA和ACH神经元的组织 前颞叶切除术标本的杏仁核可视化 项目6中的免疫细胞化学。动物实验检查获得的和 项目1至6中的遗传癫痫 人类颞叶癫痫和新的可测试假设和新的可检验假设 少年肌阵挛性癫痫。 项目7和8寻求染色体基因座 通过连锁分析与31个表型血的连锁分析的少年肌阵挛性癫痫 标记和20个限制片段长度多态性。 项目9是 为人类癫痫和计划开发候选基因标记 通过阻断基因的表达，工程师的癫痫的新遗传模型 用于谷氨酸脱羧酶或GABA受体。 通过这九个 相互加固的组件项目，对分子的新见解 获得的生化病变和癫痫易感性的机制 将获得人类癫痫的基因。