EAAT3 Contribution to Glutamate Uptake in the Hippocampus

EAAT3 对海马谷氨酸摄取的贡献

• 批准号: 7602989
• 负责人: Melissa A Herman
• 金额: $ 3.71万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7602989
• 关键词: Affinity; Amino Acid Transporter; Area; Brain; Cells; Communication; D Aspartate; Dendritic Spines; Diamond; EAAT3; Excision; Excitatory Amino Acids; Exposure to; Extracellular Space; Genes; Glutamate Receptor; Glutamate Transporter; Glutamates; Goals; Hippocampus (Brain); Interneurons; Ions; Knock-out; Knockout Mice; Longevity; Metabotropic Glutamate Receptors; Methods; Monitor; Mus; Neuraxis; Neuroglia; Neurons; Neurotransmitters; Phenotype; Play; Prevention; Research; Role; Seizures; Shapes; Slice; Supporting Cell; Synapses; Synaptic Cleft; Synaptic Transmission; Testing; Work; aspartate receptor; brain tissue; cell type; density; excitatory neuron; excitotoxicity; extracellular; gamma-Aminobutyric Acid; hippocampal pyramidal neuron; insight; neuron loss; neurotoxic; neurotoxicity; postsynaptic; prevent; receptor; response; uptake

DESCRIPTION (provided by applicant): Removal of the excitatory neurotransmitter glutamate from the synaptic cleft and extracellular space is critical in preventing excitotoxicity and neuronal cell death. Glutamate is cleared by excitatory amino acid transporters (EAATs). These EAATs are expressed on both neurons and glial cells in the central nervous system, and they work by harnessing the electrochemical energy of ions to drive glutamate translocation into the cell. Glial cell EAAT function is known to be crucial for glutamate clearance in the brain; however, the role of neuronal EAATs in specific brain areas, such as the hippocampus, has not been clearly defined. CA1 pyramidal neurons express low levels of a neuron specific subtype, EAATS; nonetheless conventional electrophysiological methods have been unable to detect EAATS functionality. The long-term goal of this application is to dissect the role of neuronal EAATS in the hippocampus and elucidate its effect on synaptic transmission. By using a highly sensitive electrophysiological approach, this project will attempt to detect EAATS functionality in hippocampal neurons. The aims of this proposal are 1) to determine transporter density differences between subpopulations of hippocampal neurons and 2) to examine the effects of EAATS on synaptic transmission in the hippocampus. Glutamate, the most abundant excitatory neurotransmitter in the brain, stimulates communication between neurons and plays a crucial role in brain function; however, in excess, glutamate can have neurotoxic effects resulting in neuronal cell death. To avoid this problem, neurons and glia, neuronal support cells, employ glutamate transport molecules, which actively transport the glutamate molecules into the cells and prevent neurotoxicity. The majority of research to date has focused on glutamate transporter subtypes expressed on glial cells, but little is known about the specific function of neuronal transporters, in particular, those expressed on neurons in the hippocampus. Deciphering the role played by neuronal glutamate transporters in the hippocampus will provide useful insight into normal brain function and prevention of excess glutamate neurotoxicity.

描述（由申请人提供）：从突触间隙和细胞外间隙去除兴奋性神经递质谷氨酸对于防止兴奋性毒性和神经元细胞死亡至关重要。谷氨酸被兴奋性氨基酸转运蛋白（EAATs）清除。这些eaat在中枢神经系统的神经元和神经胶质细胞上表达，它们通过利用离子的电化学能量驱动谷氨酸转移到细胞中。已知神经胶质细胞EAAT功能对大脑中的谷氨酸清除至关重要；然而，神经元eaat在特定大脑区域（如海马体）中的作用尚未明确界定。CA1锥体神经元低水平表达神经元特异性亚型EAATS；尽管如此，传统的电生理方法仍无法检测到EAATS的功能。本应用程序的长期目标是剖析神经元EAATS在海马中的作用，并阐明其对突触传递的影响。通过使用高灵敏度的电生理方法，本项目将尝试检测海马神经元中的EAATS功能。本研究的目的是：1)确定海马神经元亚群之间转运体密度的差异；2)检验EAATS对海马突触传递的影响。谷氨酸是大脑中最丰富的兴奋性神经递质，刺激神经元之间的交流，在大脑功能中起着至关重要的作用；然而，过量的谷氨酸会产生神经毒性作用，导致神经元细胞死亡。为了避免这个问题，神经元和神经胶质细胞（神经元支持细胞）利用谷氨酸转运分子，主动将谷氨酸分子转运到细胞内，防止神经毒性。迄今为止，大多数研究都集中在神经胶质细胞上表达的谷氨酸转运蛋白亚型，但对神经元转运蛋白的具体功能，特别是海马神经元上表达的转运蛋白的功能知之甚少。破译神经元谷氨酸转运体在海马体中的作用将为了解正常脑功能和预防过量谷氨酸神经毒性提供有用的见解。