Role of neurotrophin receptor p75 in psychiatric diseases

我们研究了神经营养因子，如脑源性神经营养因子及其受体在精神疾病中的作用。在这项研究中，我们产生了新的转基因小鼠，它们在前脑中特异性地过表达p75^&lt；NTR&gt；。对转基因小鼠进行Southern杂交鉴定。Western blotting和免疫组织化学染色确定转基因的表达模式。在这些分析中，我们观察到p75^&lt；NTR&gt；蛋白在海马体和皮质中的水平很高，但在小脑中没有。根据尸检结果，成年转基因小鼠的大脑大体形态正常。我们与理研生物资源中心老鼠表型分析技术与开发团队进行了行为分析方面的合作研究。通过光暗转换、开场试验、笼养活动试验、被动回避试验、尾部悬吊试验、热板试验、甩尾试验对转基因小鼠进行评价。然后，他们表现出过度活跃。此外，我们在原始样本和Meta分析中报告了支持p75^&lt；ntr&gt；Ser205Leu多态与MDD之间关联的证据。

We have investigated the role of neurotrophins such as brain-derived neurotrophic factor and their receptors in psychiatric disease. In this study, we generated novel transgenic mice that overexpress p75^<NTR> specifically in the forebrain. Transgenic mice were identified based on southern blot analysis. Western blotting and immunohistochemical staining were used to determine the expression pattern of the transgene. We observed the very high levels of p75^<NTR> protein in the hippocampus and cortex lines, but not in cerebellum in these analyses. According to the results of autopsy, the general morphology of brains of adult transgenic mice appeared normal. We have been conducted cooperative research on behavioral analysis with technology and Development Team for Mouse Phenotype Analysis, RIKEN BioResource Center. Our transgenic mice were estimated by light/dark transition, open-field test, home-cage activity test, passive avoidance test, tail suspension test, hot-plate test, tail-flick test. Then, they showed hyper-activity. Furthermore, we reported evidence supporting the association between the Ser205Leu polymorphism of p75^<NTR> and MDD in our original sample and in the meta-analysis.