Role of complexin II in astrocytes

复合蛋白 II 在星形胶质细胞中的作用

• 批准号: 261915-2009
• 负责人: Hazell, Alan
• 金额: --
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=456169
• 关键词: Role; complexin; II; astrocytes

Complexins constitute a family of cytosolic proteins that are involved in the regulation of neurotransmitter release. Complexin I is considered a marker of inhibitory synapses, while complexin II (Cpx II) labels predominantly excitatory nerve terminals. Although it is clear that neurotransmitter release occurs at the presynaptic terminal, recent evidence suggest that astrocytes possess the same neuronal machinery used for synaptic vesiclar release. Since Cpx II is an integral part of this neuronal machinery, we plan to study its role in the release of glutamate from these glial cells. The research project will address hypotheses that consider 1) Cpx II is present in astrocytes and regulates the release of glutamate from these cells, 2) Cpx II II modulates synaptic neurotransmission, 3) Oxidative stress influences Cpx II-mediated glutamate release, and 4) Cpx II regulates a novel and distinct form of astrocytic glutamate release that is different to other types of glutamate release operating under conditions of pathology. These issues will be addressed using primary cultures of astrocytes and neurons, in which knockdown of Cpx II gene expression will be produced and consequential genomic effects of altered Cpx II function will be identified in astrocytes and neurons along with energy metabolism changes. We are confident this research project will not only increase our understanding of the role of complexins in astrocyte function, but will also provide new insight into the significance of glutamate release from these cells, the influence of this process on excitatory neurotransmission, and its vulnerability under pathological conditions.

复合体是一类参与调节神经递质释放的胞浆蛋白家族。复合素I被认为是抑制性突触的标志，而复合素II(CPX II)主要标记兴奋性神经末梢。虽然神经递质的释放显然发生在突触前终末，但最近的证据表明，星形胶质细胞拥有与突触囊泡释放相同的神经机制。由于CPX II是这一神经机制的组成部分，我们计划研究它在这些神经胶质细胞释放谷氨酸中的作用。该研究项目将针对如下假设：1)CPX II存在于星形胶质细胞中并调节这些细胞中谷氨酸的释放，2)CPX II II调节突触神经传递，3)氧化应激影响CPX II介导的谷氨酸释放，以及4)CPX II调节一种不同于在病理条件下运行的其他类型的谷氨酸释放的新型和独特的星形细胞谷氨酸释放。这些问题将通过星形胶质细胞和神经元的原代培养来解决，在这些培养中，将产生CPX II基因表达的下调，并将随着能量代谢的变化而在星形胶质细胞和神经元中确定相应的CPX II功能改变的基因组效应。我们相信，这一研究项目不仅将增加我们对复合素在星形胶质细胞功能中的作用的了解，还将为这些细胞释放谷氨酸的意义、这一过程对兴奋性神经传递的影响以及在病理条件下的脆弱性提供新的见解。