Applied Neurotherapeutics Research Group, UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.
Proteomics. 2011 Nov;11(21):4189-201. doi: 10.1002/pmic.201100072. Epub 2011 Oct 17.
Information storage in the brain depends on the ability of neurons to alter synaptic connectivity within key circuitries such as the hippocampus. Memory-associated synaptic plasticity is mediated by a temporal cascade of de novo protein synthesis and altered protein processing. Here, we have used two-dimensional difference in gel electrophoresis (2-D DIGE) to investigate memory-specific protein changes in the hippocampal dentate gyrus at increasing times following spatial learning. We identified 42 proteins that were significantly regulated in the first 24 h of spatial memory consolidation. Two distinct waves of protein expression regulation were evident, at 3 and 12 h post-learning and this is in agreement with studies employing inhibitors of global translation. Functional classification of the memory-associated proteins revealed that the majority of regulated proteins contributed either to cellular structure or cellular metabolism. For example, actins, tubulins and intermediate filament proteins, core proteins of the three major cytoskeletal components, were dynamically regulated at times that suggest a role in memory-associated synaptic reorganization. Increased proteasome-mediated protein degradation was evident in the early post-training period including the down-regulation of phosphoprotein enriched in astrocytes 15 kDa, a key inhibitor of extracellular signal-regulated kinase signaling. Some of the most substantial protein expression changes were observed for secreted carrier proteins including transthyretin and serum albumin at 6-12 h post-learning, regulations that could serve an important role in increasing the supply of retinoic acid and thyroid hormone, key synaptic plasticity-promoting signals in the adult brain. Together these observations provide further insight into protein level regulations occurring in the hippocampus during spatial memory consolidation.
信息存储在大脑中依赖于神经元改变关键回路（如海马体）中突触连接的能力。与记忆相关的突触可塑性是由新的蛋白质合成和蛋白质加工改变的时程级联来介导的。在这里，我们使用二维差异凝胶电泳（2-D DIGE）来研究空间学习后不同时间点海马齿状回中与记忆相关的蛋白质变化。我们发现了 42 种在空间记忆巩固的头 24 小时内显著调节的蛋白质。在学习后 3 小时和 12 小时有明显的两个不同的蛋白质表达调控波，这与使用全局翻译抑制剂的研究结果一致。记忆相关蛋白的功能分类表明，大多数调节蛋白要么参与细胞结构，要么参与细胞代谢。例如，肌动蛋白、微管蛋白和中间丝蛋白，这三种主要细胞骨架成分的核心蛋白，在记忆相关的突触重组过程中，其表达的动态调节时间暗示了它们可能发挥作用。在训练后的早期阶段，蛋白酶体介导的蛋白质降解明显增加，包括富含星形胶质细胞的磷酸蛋白 15 kDa 的下调，这是细胞外信号调节激酶信号的关键抑制剂。在学习后 6-12 小时，一些分泌载体蛋白的蛋白质表达变化最大，包括转甲状腺素蛋白和血清白蛋白，这些调节可能在增加视黄酸和甲状腺激素的供应方面发挥重要作用，视黄酸和甲状腺激素是成年大脑中促进突触可塑性的关键信号。总之，这些观察结果为空间记忆巩固过程中海马体中发生的蛋白质水平调节提供了进一步的深入了解。
