不同碳纳米材料对星形胶质细胞神经递质稳态的影响及其机制研究

项目名称： 不同碳纳米材料对星形胶质细胞神经递质稳态的影响及其机制研究

项目编号： No.21477004

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 化学工业

项目作者： 郭新彪

作者单位： 北京大学

项目金额： 80万元

中文摘要： 碳纳米材料（CNMs）的广泛应用可能通过环境污染因素和神经生物医学应用两方面增加人体脑组织对其暴露的风险。然而CNMs对中枢神经系统的作用及分子机制目前还不清楚。本项目在间隙连接半通道和腺苷酸受体参与星形胶质细胞神经递质谷氨酸和ATP稳态调节的研究基础上，结合不同CNMs安全性评价的需求，评价单壁碳纳米管、聚乙二醇修饰的单壁碳纳米管、多壁碳纳米管、石墨烯及氧化石墨烯对体外培养的星形胶质细胞谷氨酸和ATP释放的影响及其作用特征，同时探讨CNMs对间隙连接半通道和腺苷酸受体的激活效应及其在谷氨酸和ATP释放中的作用，以阐明CNMs对星形胶质细胞神经递质稳态的影响及其机制；另外，进一步开展谷氨酸和ATP稳态改变对神经元细胞的影响，揭示CNMs神经毒性作用的分子机制；同时比较不同碳纳米材料的效应和特征，为CNMs的设计改进和神经生物医学的安全应用提供科学依据。

中文关键词： 碳纳米材料；神经递质；半通道；星形胶质细胞；神经毒性

英文摘要： Carbon nanomaterials (CNMs) have gained great attentions by their applications in industrial and biomedical fields, including the applications in therapy and diagnosis of central nervous system disease. The potential of CNMs to enter into brain tissue raises increasing concerns about their neurotoxicity. However, the effects of CNMs on central nervous system and the underlying mechanisms are still unclear. Based on the evidence that hemichannels involve the regulatory mechanisms of glutamate and ATP homeostasis of astrocytes, we will investigate whether different CNMs (single-walled carbon nanotubes, polyethylene glycol modified single-walled carbon nanotubes, multi-walled carbon nanotubes, graphene and graphene oxide) could regulate glutamate and ATP release from cultured astrocytes, and the involvement of hemichannels and purinergic receptors in the release mechanism. In addition, We will evaluate the effects of CNMs-induced glutamate and ATP release from astrocytes on neuronal cells. Our study will provide novel evidence about the mechanisms for neurotoxicity caused by CNMs. It is also expected to be useful for safety evaluation of CNMs and the development of nanostructure-based medical technology for therapy and diagnosis of brain diseases.

英文关键词： Carbon nanomaterials;Neurotransmitter;Hemichannel;Astrocyte;Neurotoxicity