Reelin Exerts Structural, Biochemical and Transcriptional Regulation Over Presynaptic and Postsynaptic Elements in the Adult Hippocampus.
Reelin Exerts Structural, Biochemical and Transcriptional Regulation Over Presynaptic and Postsynaptic Elements in the Adult Hippocampus.
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DOI：
10.3389/fncel.2016.00138
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发表时间：
2016
影响因子：
5.3
通讯作者：
Martínez A
中科院分区：
文献类型：
--
作者：
Bosch C;Muhaisen A;Pujadas L;Soriano E;Martínez A
Reelin调节发育中大脑的神经元定位和突触发生，以及成人大脑的可塑性。在这里，我们使用过表达Reelin的转基因小鼠（Reelin-OE小鼠）进行全面解剖这种蛋白质对成年海马树突棘和轴突终末的结构和生化特征的影响。电子显微镜（EM）显示更高的密度的突触和结构复杂性的前和突触后元件在转基因小鼠比野生型小鼠。树突棘有较大的棘器，这与突触足蛋白的重新分配。在Reelin-OE小鼠中观察到的大多数变化在阻断转基因表达后是可逆的，因此支持观察到的表型的特异性。蛋白质印迹和转录分析没有显示突触前或突触后蛋白质，包括SNARE蛋白，谷氨酸受体，支架和信号蛋白的表达的重大变化。然而，EM免疫金分析显示，NMDA受体亚基NR 2a和NR 2b，和p-Cofilin显示从突触到突触外池的再分布。与以前的研究一起，目前的研究结果表明，Reelin调节成人海马突触的结构和生化特性，通过增加其密度和形态的复杂性，并通过修改的分布和贩运的主要mammatergic组件。
Reelin regulates neuronal positioning and synaptogenesis in the developing brain, and adult brain plasticity. Here we used transgenic mice overexpressing Reelin (Reelin-OE mice) to perform a comprehensive dissection of the effects of this protein on the structural and biochemical features of dendritic spines and axon terminals in the adult hippocampus. Electron microscopy (EM) revealed both higher density of synapses and structural complexity of both pre- and postsynaptic elements in transgenic mice than in WT mice. Dendritic spines had larger spine apparatuses, which correlated with a redistribution of Synaptopodin. Most of the changes observed in Reelin-OE mice were reversible after blockade of transgene expression, thus supporting the specificity of the observed phenotypes. Western blot and transcriptional analyses did not show major changes in the expression of pre- or postsynaptic proteins, including SNARE proteins, glutamate receptors, and scaffolding and signaling proteins. However, EM immunogold assays revealed that the NMDA receptor subunits NR2a and NR2b, and p-Cofilin showed a redistribution from synaptic to extrasynaptic pools. Taken together with previous studies, the present results suggest that Reelin regulates the structural and biochemical properties of adult hippocampal synapses by increasing their density and morphological complexity and by modifying the distribution and trafficking of major glutamatergic components.