Differential proteome profiling in the hippocampus of amnesic mice
Differential proteome profiling in the hippocampus of amnesic mice
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DOI：
10.1002/hipo.22735
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发表时间：
2017-08-01
期刊：
影响因子：
3.5
通讯作者：
Thakur, Mahendra Kumar
中科院分区：
文献类型：
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作者：
Baghel, Meghraj Singh;Thakur, Mahendra Kumar
健忘或记忆丧失与大脑老化和包括阿尔茨海默病(AD)在内的几种神经退行性病变有关。这可以由胆碱能拮抗剂东莨菪碱诱导，但其潜在的分子机制尚不清楚。这项对海马区蛋白质组图谱的研究可以为失忆症的分子机制提供概念性的见解。为了揭示这一点，我们给小鼠注射东莨菪碱以诱发记忆障碍，并通过新的物体识别测试来验证记忆障碍。利用双向凝胶电泳法和MALDI-MS/MS联用技术对海马区蛋白质组进行了分析，鉴定出了18个差异表达的蛋白质。在这些蛋白质中，与对照组相比，东莨菪碱治疗组小鼠有11个蛋白质下调，7个蛋白质上调。蛋白质组学分析表明，大多数鉴定的蛋白质都参与了代谢、催化活性和细胞骨架构筑功能。序列相互作用网络分析表明，大多数已鉴定的蛋白质与Actg1细胞骨架蛋白和Vdac1能量转运蛋白具有共同的相关性。此外，相互作用图分析表明，Fascin1和Coron1b分别与Actg1相互作用，并调节肌动蛋白细丝的动力学。在遗忘症小鼠中，Vdac1的表达显著下调，并与相互作用网络中的其他蛋白相互作用。因此，我们在正常幼鼠的海马区沉默了Vdac1，并在Vdac1沉默和东莨菪碱治疗的小鼠的再认记忆中发现了类似的损害。因此，这些发现表明，Vdac1介导的能量代谢和细胞骨架结构的破坏可能参与了东莨菪碱诱导的遗忘症。
Amnesia or memory loss is associated with brain aging and several neurodegenerative pathologies including Alzheimer's disease (AD). This can be induced by a cholinergic antagonist scopolamine but the underlying molecular mechanism is poorly understood. This study of proteome profiling in the hippocampus could provide conceptual insights into the molecular mechanisms involved in amnesia. To reveal this, mice were administered scopolamine to induce amnesia and memory impairment was validated by novel object recognition test. Using two-dimensional gel electrophoresis coupled with MALDI-MS/MS, we have analyzed the hippocampal proteome and identified 18 proteins which were differentially expressed. Out of these proteins, 11 were downregulated and 7 were upregulated in scopolamine-treated mice as compared to control. In silico analysis showed that the majority of identified proteins are involved in metabolism, catalytic activity, and cytoskeleton architectural functions. STRING interaction network analysis revealed that majority of identified proteins exhibit common association with Actg1 cytoskeleton and Vdac1 energy transporter protein. Furthermore, interaction map analysis showed that Fascin1 and Coronin 1b individually interact with Actg1 and regulate the actin filament dynamics. Vdac1 was significantly downregulated in amnesic mice and showed interaction with other proteins in interaction network. Therefore, we silenced Vdac1 in the hippocampus of normal young mice and found similar impairment in recognition memory of Vdac1 silenced and scopolamine-treated mice. Thus, these findings suggest that Vdac1-mediated disruption of energy metabolism and cytoskeleton architecture might be involved in scopolamine-induced amnesia.