Nesher Elimelech, Koman Igor, Gross Moshe, Tikhonov Tatiana, Bairachnaya Maryia, Salmon-Divon Mali, Levin Yishai, Gerlitz Gabi, Michaelevski Izhak, Yadid Gal, Pinhasov Albert
1] Department of Molecular Biology. Ariel University, Ariel. Israel [2] Faculty of Life Sciences. Bar-Ilan University, Ramat Gan. Israel.
Department of Molecular Biology. Ariel University, Ariel. Israel.
Sci Rep. 2015 May 22;5:10287. doi: 10.1038/srep10287.
Dominance and submissiveness are important functional elements of the social hierarchy. By employing selective breeding based on a social interaction test, we developed mice with strong and stable, inheritable features of dominance and submissiveness. In order to identify candidate genes responsible for dominant and submissive behavior, we applied transcriptomic and proteomic studies supported by molecular, behavioral and pharmacological approaches. We clearly show here that the expression of Synapsin II isoform b (Syn IIb) is constitutively upregulated in the hippocampus and striatum of submissive mice in comparison to their dominant and wild type counterparts. Moreover, the reduction of submissive behavior achieved after mating and delivery was accompanied by a marked reduction of Syn IIb expression. Since submissiveness has been shown to be associated with depressive-like behavior, we applied acute SSRI (Paroxetine) treatment to reduce submissiveness in studied mice. We found that reduction of submissive behavior evoked by Paroxetine was paired with significantly decreased Syn IIb expression. In conclusion, our findings indicate that submissiveness, known to be an important element of depressive-like behavioral abnormalities, is strongly linked with changes in Syn IIb expression.
支配和顺从是社会等级制度的重要功能要素。通过基于社会互动测试进行选择性育种，我们培育出了具有强大且稳定的、可遗传的支配和顺从特征的小鼠。为了确定与支配和顺从行为相关的候选基因，我们应用了转录组学和蛋白质组学研究，并辅以分子、行为和药理学方法。我们在此清楚地表明，与支配型和野生型小鼠相比，顺从型小鼠海马体和纹状体中突触结合蛋白II亚型b（Syn IIb）的表达持续上调。此外，交配和分娩后顺从行为的减少伴随着Syn IIb表达的显著降低。由于顺从已被证明与类似抑郁的行为有关，我们应用急性选择性5-羟色胺再摄取抑制剂（帕罗西汀）治疗以减少所研究小鼠的顺从行为。我们发现，帕罗西汀引起的顺从行为减少与Syn IIb表达的显著降低相关。总之，我们的研究结果表明，顺从作为类似抑郁行为异常的一个重要因素，与Syn IIb表达的变化密切相关。
