肌动蛋白的氧化还原对神经元突触可塑性具有重要调节作用。最近研究发现，肌动蛋白第44和第47位甲硫氨酸受氧化形成亚砜会使微丝解聚，而硒蛋白R能够在体外使上述亚砜得到还原，从而恢复肌动蛋白的聚集能力。本项目组发现，在小鼠脑组织中SelR特异性表达于海马CA1区的Orien stratum/Alveus，这一区域与海马组织与其他周围系统间的信息传递有关。另外，在3×Tg AD模型小鼠脑组织中SelR的表达与野生型小鼠相比具有显著性的降低，这可能与AD小鼠脑组织氧化型肌动蛋白水平升高有关。因此，本项目将在3×Tg AD模型小鼠脑组织内过表达SelR，检测其对海马组织氧化型肌动蛋白水平及LTP的影响，同时对比SelR敲除小鼠与野生型小鼠海马组织LTP的差异，并利用双光子荧光显微镜检测敲低SelR对神经元突触的影响。从而说明在AD病理过程中SelR通过肌动蛋白还原能力对突触可塑性的调节作用。

The redox of actin plays an important role in the regulation of synaptic plasticity. Recently, it has been demonstrated that oxidation of the 44 and 47 methionine residues of actin to methionine-R-sulfoxide promoted F-actin depolymerization and further inhibited G-actin polymerization. Whereas, Selenoprotein R (SelR) could convert aforementioned methionine-R-sulfoxide to their reductive form, thus restoring actin the ability of aggregation. Furthermore, the works accomplished by our group showing that in mouse brain SelR was specifically expressed at the Orien stratum/Alveus of hippocampal CA1 region, where it is believed to relate with information transmission between hippocampus and other parts of limbic system. In addition, the expression of SelR was significantly down-regulated in the brain of 3×Tg AD model mice vs. their wild type counterparts. This is consistent with the up-regulation of oxidated actin level in brain of those mice. Therefore, we will assess the level of oxidated actin and the LTP after overexpression of SelR in the brain of 3×Tg AD model mice vs. control, and further compare the difference of the LTP between the SelR knockout mice and WT mice, in the meantime, we will also evaluate the impact of SelR knockdown on the synaptic plasticity by using two-photon microscopy. Consequently, we would demonstrate the involvement of SelR in regulation of synaptic plasticity during the process of AD pathology through its reductivity on actin.