Tamaki Keisuke, Kamakura Masaki, Nakamichi Noritaka, Taniura Hideo, Yoneda Yukio
Laboratories of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
Neurosci Lett. 2008 Mar 15;433(3):183-7. doi: 10.1016/j.neulet.2007.12.062. Epub 2008 Jan 11.
Traumatic stress has been believed to result in a variety of unusual alterations of the integrity and the functionality in the hippocampus. In this study, we searched for genes responsive to traumatic stress in the mouse hippocampus to elucidate the underlying mechanisms. Adult male mice were subjected to water-immersion restraint stress (WIRS) for 3h as an extremely stressful experience, followed by dissection of the hippocampus and subsequent extraction of RNA for differential display polymerase chain reaction (PCR) analysis. The actin-based molecular motor protein myosin VI (Myo6) was identified as a gene markedly upregulated by traumatic stress in the mouse hippocampus 24h after WIRS. Real-time PCR and Western blotting analyses clearly revealed a significant increase in the expression of both mRNA and corresponding protein for Myo6 in the hippocampus within 24h after WIRS, while WIRS failed to significantly affect the expression of Myo6 protein in the cerebral cortex, cerebellum and olfactory bulb. Immunohistochemistry analysis revealed that Myo6 protein was ubiquitously expressed throughout the mouse brain, with an extremely high level in the olfactory bulb. These results suggest that Myo6 may be selectively and rapidly upregulated to play a hitherto unidentified role in the maintenance of the integrity and functionality in the hippocampus after traumatic stress.
创伤应激被认为会导致海马体的完整性和功能发生各种异常改变。在本研究中,我们在小鼠海马体中寻找对创伤应激有反应的基因,以阐明其潜在机制。成年雄性小鼠经历3小时的水浸束缚应激(WIRS)作为一种极其应激的体验,随后解剖海马体并提取RNA用于差异显示聚合酶链反应(PCR)分析。基于肌动蛋白的分子运动蛋白肌球蛋白VI(Myo6)被鉴定为在WIRS后24小时小鼠海马体中因创伤应激而显著上调的基因。实时PCR和蛋白质印迹分析清楚地显示,WIRS后24小时内海马体中Myo6的mRNA和相应蛋白质的表达均显著增加,而WIRS未能显著影响大脑皮层、小脑和嗅球中Myo6蛋白质的表达。免疫组织化学分析显示,Myo6蛋白在整个小鼠大脑中广泛表达,在嗅球中水平极高。这些结果表明,Myo6可能被选择性地快速上调,以在创伤应激后海马体的完整性和功能维持中发挥迄今未被识别的作用。