Loss of MsrB1 perturbs spatial learning and long-term potentiation/long-term depression in mice
Loss of MsrB1 perturbs spatial learning and long-term potentiation/long-term depression in mice
复制标题
MsrB1 的缺失会扰乱小鼠的空间学习和长期增强/长期抑制。
DOI：
10.1016/j.nlm.2019.107104
复制
发表时间：
2019-12-01
影响因子：
2.7
通讯作者：
Li, Nan
中科院分区：
文献类型：
--
作者：
Shi, Tengrui;Yang, Yujie;Li, Nan
MsrB1属于蛋氨酸亚砜还原酶家族，因其具有硒半胱氨酸残基，故又称硒蛋白R。据报道，MsrB1在体外可以与肌动蛋白、TRPM6、聚集素和淀粉样β蛋白相互作用。因此，我们推测MsrB1在中枢神经系统中可能起重要作用。为了探讨MsrB1基因敲除对小鼠脑发育或学习行为的影响，我们对MsrB1基因缺陷小鼠的脑组织进行了组织学研究，并用Morris水迷宫和电生理方法进一步检测了这些小鼠的空间学习能力和长时突触可塑性。结果表明，除海马区星形胶质细胞增生症外，MsrB1基因缺失并不影响中枢神经系统的整体发育，但可导致小鼠空间学习能力丧失，脑片LTP/LTD表达严重受损，突触蛋白PSD95、SYP、GIuN2A和G1uN2B表达下调，CaMKII在286(287)位的磷酸化水平较野生型小鼠显著降低。综上所述，这些结果表明，MsrB1对小鼠的空间学习和LTP/LTD诱导是必需的，MsrB1相关的氧化还原稳态可能参与调节CaMKII的磷酸化。
MsrBl belongs to the methionine sulfoxide reductase family, it is also known as selenoprotein R for the sake of possessing a selenocysteine residue. It has been reported that MsrBl could interact with actin, TRPM6, clusterin, and amyloid-beta in vitro. Thus, we presumed that MsrBl may play an important role in central nervous system. To examine whether MsrB1 knockout has any effects on brain development or learning behavior, we carried out histological study on brains of MsrBl deficient mice, and further tested spatial learning ability and long-term synaptic plasticity of these mice by using Morris water maze and electrophysiological methods. It was observed that loss of MsrBl did not perturb the overall development of central nervous system except for the astrogliosis in hippocampus, however, it led mice to be incapable in spatial learning and severe impairments in LTP/LTD expression in CAl of brain slices, along with the down-regulation of the synaptic proteins including PSD95, SYP, GIuN2A and G1uN2B, as well as the dramatic decrease of CaMKIIs phosphorylation at 286(287) compared with wild type mice. Taken together, these results suggest that MsrBl is essential for mice spatial learning and LTP/LTD induction, and the MsrBl related redox homeostasis may be involved in regulating the phosphorylation of CaMKIIs.