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Role for glia-neuron interaction in the brain ageing and longevity

胶质神经元相互作用在大脑衰老和长寿中的作用

基本信息

批准号：
BB/K009192/1
负责人：
Yuriy Pankratov
金额：
$ 64.33万
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：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FK009192%2F1
关键词：
Role glia neuron interaction brain

项目摘要

Maintaining brain function is very important for mental and physical health of individuals. The brain is composed of two major types of cells: neurons which transmit electrical signals and glial cells which maintain the wellbeing and function of neurons.Recent discoveries highlighted the importance of interaction between neuronal and glial cells for many brain functions, like memory and cognition. Glial cells turned out to an active player in the brain. They can communicate with each other and neurons as well. They are capable to release neurotransmitters - small molecules transmitting chemical signals between cells. Glial cells also have receptors to these neurotransmitters - special proteins located in their membrane. One of the most important neurotransmitters that mediate bi-directional communication between neurons and glial cells are glutamate and adenosine-3-phosphate (ATP).Through the course of life, glial cells maintain the wellbeing of neurons and protect brain tissue from neuronal over-excitability. Glia malfunction is related to many brain disorders such as ischemia, stroke, epilepsy, Alzheimer's disease and even effects of drug abuse. There is growing evidence, including our preliminary results, that the function of glial cells and their communication with neurons can change with age and these changes underlie frailty of the aged brain. Thus, glia-neuron communication may be of crucial importance for brain longevity and healthy ageing. However, age-related changes in astroglial signalling and their impact on brain longevity remain almost unexplored. Research teams headed by the applicants have experience of whole-cell electrophysiological recordings and fluorescent imaging in brains of old animals. Our data on age-related alterations of glutamate- and ATP- mediated glial signalling have been recently published in the Ageing Cell - a leading international journal in the field. We have also developed a range of novel optogenetic and molecular tools for the study of astrocyte-to-neurone communication. The power of this approach is illustrated by our recent paper in Science which demonstrates another role for release of ATP from glial cells in the brain control of respiration. We wish to capitalise on this potential and propose a quantitative study of astrocytic control of age-related changes in communication between neurons and glial cells brain signaling.The outcome of this research will be a new understanding of the role of astroglial cells in brain function and brain longevity. Results obtained will also contribute to further understanding of the physiology of ageing and will help to develop novel approaches for therapeutic interventions in neurological disorders and strategies for promotion of successful ageing

维持大脑功能对个人的身心健康非常重要。大脑由两种主要类型的细胞组成：神经元和神经胶质细胞，神经元传递电信号，神经胶质细胞维持神经元的健康和功能。最近的发现强调了神经元和神经胶质细胞之间的相互作用对许多大脑功能的重要性，如记忆和认知。神经胶质细胞在大脑中扮演着积极的角色。它们可以相互交流，也可以与神经元交流。它们能够释放神经递质-在细胞之间传递化学信号的小分子。神经胶质细胞也有这些神经递质的受体-位于其膜上的特殊蛋白质。谷氨酸和3-磷酸腺苷（ATP）是介导神经元和神经胶质细胞之间双向通讯的重要神经递质之一，在整个生命过程中，神经胶质细胞维持神经元的健康并保护脑组织免受神经元过度兴奋的影响。神经胶质功能障碍与许多脑部疾病有关，如缺血、中风、癫痫、阿尔茨海默病，甚至药物滥用的影响。越来越多的证据，包括我们的初步结果，表明胶质细胞的功能及其与神经元的通讯可以随着年龄的变化而变化，这些变化是老年大脑脆弱的基础。因此，胶质神经元通信可能对大脑寿命和健康老龄化至关重要。然而，星形胶质细胞信号传导中与年龄相关的变化及其对大脑寿命的影响仍然几乎未被探索。以申请人为首的研究团队拥有老年动物大脑全细胞电生理记录和荧光成像的经验。我们关于年龄相关的谷氨酸和ATP介导的神经胶质细胞信号转导的改变的数据最近发表在该领域的国际领先期刊《衰老细胞》上。我们还开发了一系列新颖的光遗传学和分子工具，用于研究星形胶质细胞与神经元的通讯。我们最近在《科学》杂志上发表的一篇论文说明了这种方法的威力，该论文证明了神经胶质细胞释放ATP在大脑控制呼吸中的另一个作用。我们希望利用这一潜力，并提出一个定量研究星形胶质细胞控制的年龄相关的变化之间的沟通神经元和神经胶质细胞脑signaling.The研究的结果将是一个新的理解星形胶质细胞在脑功能和脑寿命的作用。所获得的结果还将有助于进一步了解衰老的生理学，并将有助于开发神经系统疾病治疗干预的新方法和促进成功衰老的战略。

项目成果

期刊论文数量（10）

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.

Current technical approaches to brain energy metabolism.

DOI：
10.1002/glia.23248
发表时间：
2018-06
期刊：
Glia
影响因子：
6.2
作者：
Barros LF;Bolaños JP;Bonvento G;Bouzier-Sore AK;Brown A;Hirrlinger J;Kasparov S;Kirchhoff F;Murphy AN;Pellerin L;Robinson MB;Weber B
通讯作者：
Weber B

Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging