WDR1与小鼠精神分裂样阴性症状呈正相关性

目的 探讨海马CA1区条件性敲除WDR1与小鼠精神分裂样阴性症状的关系,并进一步分析其潜在神经机制.方法 利用分子生物学手段,构建海马CA1区的WDR1条件性敲除小鼠CA1-Cre; WDR1flox/flox(CKO)],结合做窝行为学手段、免疫荧光等实验方法观察分析CA1区WDR1在精神分裂样阴性症状中的作用.结果 ①脑片免疫荧光的结果显示WDR1在CKO小鼠中敲除成功;②做窝实验结果显示:WDR1 CKO小鼠做窝质量明显高于WDR1flox/flox小鼠(WT组);③培养海马神经元,免疫荧光染色法显示,CKO小鼠的树突棘密度明显增加.结论 实验结果表明敲除 WDR1能够增加海马CA1区神经元的树突棘,并提高小鼠做窝能力,提示WDR1与小鼠精神分裂样阴性症状呈正相关.

WDR1 positively correlated with schizophrenia-like negative symptoms

Objective To investigate the relationship between the conditional knockout WDR1 in the hippocampal CA1 region and schizophrenia-like negative symptoms in mice, and to analyze the underlying neural mechanisms. Methods By means of molecular biology, conditional knockout (CKO) mice with CA1-specific deletion of WDR1 by Cre-loxp system(CAl-Cre; WDRlflox/flox), combined with nest building behavioral analysis, cell biology assay and immunohistochemistry to analyze the role of WDR1 in negative-like symptoms of schizophrenia. Results ① Slices immunofluorescence showed WDR1 decreased in WDR1 CKO mice;② Nest building behavioral test results showed that the nest quality was significantly higher in CKO mice than WDR1flox/flox mice (WT group);③ Cell immunofluorescence showed that dendritic spine density was significantly increased in CKO mice. Conclusion WDR1 deficiency could increase the number of dendritic spines of neurons in hippocampal CA1 region and improve the ability of nest building, suggesting that WDR1 is negatively correlated with the schizophrenia-like negative symptoms.