Characterizing the Function of miRNAs in Neural Development, Synaptic Plasticity and Schizophrenia.

miRNAs与精神分裂症有关。编码miRNA或miRNA生物发生机制中的组分的基因突变与精神分裂症风险增加相关。假设miRNA表达在精神分裂症中是异常的。使用微阵列和定量PCR，几个研究小组检测了精神分裂症患者死后大脑中miRNA的表达，并一致地检测到miRNA表达的变化。然而，大脑中的发现并不一致。在本项目中，我们采用了新一代测序技术，该技术提供了优越的上级灵敏度和可定量性，以鉴定在精神分裂症患者大脑中差异表达的miRNA。我们还分析了精神药物和吸烟对miRNA表达的影响。利用生物信息学，我们发现在精神分裂症中差异表达的miRNAs的靶点富含编码突触蛋白和与精神分裂症风险相关的基因。在本报告期间，我们在人类IPSC衍生的神经元中表达并敲低了精神分裂症患者中改变的miRNA。我们研究了这些神经元的基本生物物理特性、微型突触释放和突触蛋白的表达。

miRNAs have been implicated in schizophrenia. Mutations in genes encoding miRNAs or components in the miRNA biogenesis machinery are associated with increased risk for schizophrenia. It is hypothesized that miRNA expression is aberrant in schizophrenia. Using microarray and quantitative PCR, several groups have examined miRNA expression in postmortem brains of people with schizophrenia, and consistently detected miRNA expression change. However, the findings in the brains have been inconsistent. In this project, we employed the next-generation sequencing technology which offers superior sensitivity and quantifiability to identify miRNAs that are differentially expressed in schizophrenic brains. We also analyzed the effect of psychiatric medications and tobacco smoking on miRNA expression. Using bioinformatics, we found that the targets of miRNAs differentially expressed in schizophrenia are enriched for genes encoding synaptic proteins and those associated with risk for schizophrenia. During this reporting period, we expressed and knocked down a miRNA altered in people with schizophrenia in human IPSC-derived neurons. We examined basic biophysical properties, miniature synaptic release, and the expression of synaptic proteins in these neurons.