Borovok Natalia, Nesher Elimelech, Reichenstein Michal, Tikhonova Tatiana, Levin Yishai, Pinhasov Albert, Michaelevski Izhak
Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel-Aviv, Israel.
Department of Molecular Biology, Ariel University, Ariel, Israel.
Proteomics Clin Appl. 2017 Dec;11(11-12). doi: 10.1002/prca.201700089. Epub 2017 Sep 27.
Psychiatric conditions, in many cases, arise from social interactions necessary for optimal mental functioning. Dominance and submissiveness are two opposite poles of behavior, stemming from processes of social interactions between members inside one group or species. Extreme dominance and submissiveness expressions in humans is accompanied by mental impairments, including mania and depression. Here, taking advantage of animals bred selectively for traits of dominance and submissiveness, we assess protein expression profiles in dominant and submissive mice in the context of social interaction.
Proteins extracted from hippocampi of naïve and social interaction subjected dominant, submissive and wild type mice (15 mice per each group) are quantified using label-free quantitative LC/MS/MS analysis. Complexity of social interaction-related protein expression is resolved by factor analysis and enriched with GO and protein-protein interaction functional network analyses.
In total, 1146 proteins exhibiting expression changes in the wild type mice, as well as dominant and submissive mice are enriched in protein datasets responsible for: 1) socially triggered dominance (90 proteins), 2) inherent submissiveness (75 proteins), 3) socially triggered submissiveness (117 proteins), and 4) social interaction triggered protein expression changes, related to resilience/adaptation to stress (69 proteins). Among the most enriched categories, extensive changes are found in proteins related to presynaptic release, ion channel regulation, circadian rhythm, MAPK, ErbB and NF-kB pathways.
Data extracted from this first extensive proteomic study of a social interaction paradigm may facilitate decoding of molecular mechanisms responsible for pathogenesis of psychiatric disorders.
在许多情况下，精神疾病源于最佳心理功能所必需的社会互动。支配和顺从是行为的两个相反极点，源于一个群体或物种内部成员之间的社会互动过程。人类中极端的支配和顺从表达伴随着精神障碍，包括躁狂和抑郁。在此，我们利用为支配和顺从特征而选择性培育的动物，在社会互动的背景下评估显性和隐性小鼠的蛋白质表达谱。
使用无标记定量液相色谱/串联质谱分析对从未接触过社会互动以及经历过社会互动的显性、隐性和野生型小鼠（每组15只小鼠）的海马体中提取的蛋白质进行定量。通过因子分析解析社会互动相关蛋白质表达的复杂性，并通过基因本体（GO）和蛋白质-蛋白质相互作用功能网络分析进行富集。
总共1146种在野生型小鼠以及显性和隐性小鼠中表现出表达变化的蛋白质在负责以下方面的蛋白质数据集中得到富集：1）社会触发的支配（90种蛋白质），2）固有顺从（75种蛋白质），3）社会触发的顺从（117种蛋白质），以及4）与对应激的恢复力/适应相关的社会互动触发的蛋白质表达变化（69种蛋白质）。在最富集的类别中，与突触前释放、离子通道调节、昼夜节律、丝裂原活化蛋白激酶（MAPK）、表皮生长因子受体（ErbB）和核因子κB（NF-κB）途径相关的蛋白质发生了广泛变化。
从这项首次对社会互动范式进行的广泛蛋白质组学研究中提取的数据可能有助于解码导致精神疾病发病机制的分子机制。
