Snk-SPAR通路介导微波辐射后树突棘可塑性异常的机制研究

项目名称： Snk-SPAR通路介导微波辐射后树突棘可塑性异常的机制研究

项目编号： No.61501492

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 无线电电子学、电信技术

项目作者： 李海娟

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 21万元

中文摘要： 微波辐射致学习记忆障碍的机制尚不明确。树突棘可塑性与学习记忆功能密切相关，其中Snk-SPAR 通路在活化依赖性突触重构中起关键作用。研究表明，微波辐射可致海马神经元树突棘密度降低，形状改变，树突片段长度减少，因此推测Snk-SPAR 通路在微波辐射所致的树突棘形态和功能异常中发挥重要作用。本项目拟以Snk-SPAR 通路为切入点，探讨微波辐射致树突棘可塑性异常的机制。建立微波辐射致树突棘可塑性异常的动物和细胞模型，研究微波辐射对该通路中Snk、SPAR的表达及其磷酸化、SPAR泛素化降解的影响；细胞水平进一步研究微波辐射对Snk-SPAR通路上游分子CaN、CIB及Cdk5等的影响；给予关键分子拮抗剂、RNA干扰和基因转染等干预，研究微波辐射通过Snk-SPAR 通路影响树突棘形态和功能的机制。为阐明微波辐射致学习记忆障碍的机制奠定基础，并为微波辐射脑损伤的防治提供新的候选靶点。

中文关键词： 微波；树突棘；Snk；SPAR；泛素蛋白酶系统

英文摘要： The mechanisms for learning and memory deficits induced by microwave radiation remain undetermined. Studies suggested that plasticity of dendritic spines is intimately related to learning and memory ability and many central nervous system diseases in which Snk-SPAR pathway critically adjusted the synaptic reorganization. In the previous study, it was found that microwave radiation could decrease the density of dendritic spines and the length of dendrites per neuron and influence the morphology of dendritic spines in hippocampus. Accordingly, we assumed that Snk-SPAR pathway may be involved in the process of the abnormalities of dendritic spines morphology and function induced by microwave exposure. In this study, taking Snk-SPAR pathway as a target, we aimed to explore the mechanisms of microwave exposure-induced dendritic spines plasticity abnormality. Firstly, we planned to establish the animal and hippocampal neuron models, and evaluate the.effects of microwave on the expression and phosphorylation of Snk and SPAR, ubiquitination of SPAR. Secondly, in the hippocampal neuron model, we planned to assess the effects of the radiation on upstream molecules of Snk-SPAR pathway (CaN、CIB、Cdk5、RasGRF1、SynGAP and PDZGEF1) and ubiquitin-proteasome pathway (SCFβ-TRCP). Then RNA interference, gene transfection methods and inhibitors of Snk, CaN, Cdk5 molecules and Ubiquitin-proteasome would be applied to interfere in the Snk-SPAR pathway to further study the role of Snk-SPAR pathway in the process. To conclude, the purpose of this study was to clarify the role of Snk-SPAR pathway in the learning and memory function deficits induced by the microwave radiation and provide new candidate targets for prevention and treatment of brain injury by microwave radiation.

英文关键词： microwave;dendritic spine;Snk;SPAR;ubiquitin proteasome system