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Properties and function of astroglial NMDA receptors: implications for plasticity of neuron-glial communication in the neocortex

星形胶质细胞 NMDA 受体的特性和功能：对新皮质神经元-胶质细胞通讯可塑性的影响

基本信息

批准号：
BB/F021445/1
负责人：
Yuriy Pankratov
金额：
$ 48.74万
依托单位：
University of Warwick
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF021445%2F1
关键词：
Properties function astroglial NMDA receptors

项目摘要

Brain function is mediated by two classes of cell, the electrically excitable neurons and electrically non-excitable glial cells. For more than a century, glial cells were thought to play the role of structural and nutritional support neurons. Even their name means 'glue' (in Greek). Glial cells outnumber neurons 10:1 and this gives rise to the popular cliché that 'we use the potential of our brain only for 10 %'. The view on the function of glial cells / astrocytes and oligodendrocytes has undergone revolutionary change in recent years. Today glial cells are recognized as competent participants of brain communications and the interest of neuroscience laboratories in astrocyte and oligodendrocyte studies is rapidly growing. Glial cells have also become new targets for developing therapeutic agents for treatment of neurodegenerative disorders. My project will study signals generated in cortical astrocytes by glutamate - a very important transmitter of neuronal communications. Data obtained in the last decade have demonstrated the capability of glial cells to generate and receive signals mediated by 'classical' neurotransmitters such as glutamate. The actions of glutamate as a transmitter are mediated by several types of receptors. Of these, one of the most important is the NMDA receptor. These are critical for many brain functions, like memory and cognition and many brain pathologies such as ischemia and various neurodegenerative disorders. Until recently, NMDA receptors were thought not to be very important for the function of glial cells. The few groups who have undertaken work in this area have provided new insights. They have shown that glial NMDA receptors have properties different from neuronal ones and contribute to signaling between neurons and glial cells. Glial NMDA receptors may also be promising targets for the development of novel therapeutic agents for neurological disorders. However, this is hampered by incomplete current knowledge about the properties and functions of astroglial NMDA receptors. My project will provide the first detailed investigation of properties of NMDA receptors in the cortical astrocytes and their role in the astrocyte signalling. The outcome of my research will be new understanding of the pharmacological and functional properties of glial NMDA receptors.

大脑功能由两类细胞介导，即电可兴奋神经元和电不可兴奋神经胶质细胞。一个多世纪以来，神经胶质细胞被认为扮演着结构和营养支持神经元的角色。甚至它们的名字在希腊语中的意思也是“胶水”。神经胶质细胞与神经元的数量之比为10：1，这就引出了一句流传甚广的老生常谈：“我们只用10%的时间来发挥大脑的潜能。”近年来，对胶质细胞/星形胶质细胞和少突胶质细胞功能的看法发生了革命性的变化。今天，神经胶质细胞被认为是脑通讯的合格参与者，神经科学实验室对星形胶质细胞和少突胶质细胞的研究兴趣正在迅速增长。神经胶质细胞也成为开发治疗神经退行性疾病的治疗药物的新靶点。我的项目将研究谷氨酸在大脑皮层星形胶质细胞中产生的信号--谷氨酸是神经元通讯的一种非常重要的递质。过去十年中获得的数据表明，神经胶质细胞有能力产生和接收由谷氨酸等经典神经递质介导的信号。谷氨酸作为递质的作用是由几种类型的受体介导的。其中，最重要的是NMDA受体。它们对许多大脑功能至关重要，如记忆和认知，以及许多大脑病理，如缺血和各种神经退行性疾病。直到最近，NMDA受体被认为对神经胶质细胞的功能并不是很重要。在这一领域开展工作的少数几个小组提供了新的见解。他们已经证明，神经胶质NMDA受体具有不同于神经元的特性，并有助于神经元和神经胶质细胞之间的信号传递。神经胶质细胞的NMDA受体也可能成为开发治疗神经疾病的新型药物的潜在靶点。然而，目前对星形胶质细胞NMDA受体的性质和功能的不完全了解阻碍了这一点。我的项目将首次详细研究大脑皮层星形胶质细胞中NMDA受体的特性及其在星形胶质细胞信号传递中的作用。我的研究结果将是对神经胶质细胞NMDA受体的药理和功能特性的新理解。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility.

DOI：
10.1038/ncomms5701
发表时间：
2014-08-19
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Eales, Katherine L.;Palygin, Oleg;O'Loughlin, Thomas;Rasooli-Nejad, Seyed;Gaestel, Matthias;Mueller, Juergen;Collins, Dawn R.;Pankratov, Yuriy;Correa, Sonia A. L.
通讯作者：
Correa, Sonia A. L.

Impact of Autophagy Impairment on Experience- and Diet-Related Synaptic Plasticity.