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，我们培育了一种新的转基因小鼠，在前脑特异性地过表达p75^<NTR>。利用southern blot技术鉴定转基因小鼠。Western blotting和免疫组化染色检测转基因基因的表达谱。在这些分析中，我们观察到海马和皮质线中p75^<NTR>蛋白的水平非常高，但在小脑中没有。解剖结果显示，成年转基因小鼠的大脑形态基本正常。我们与RIKEN生物资源中心的小鼠表型分析技术和开发团队进行了行为分析的合作研究。采用明暗转换、露天试验、家笼活动试验、被动回避试验、悬尾试验、热板试验、甩尾试验等方法对转基因小鼠进行评价。然后，他们表现出过度活跃。此外，我们在原始样本和荟萃分析中报告了支持p75^<NTR>的Ser205Leu多态性与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.