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

许多研究表明，精神分裂症患者的大脑有异常的基因表达，这可能是由于基因表达失调引起的。microRNAs（miRNAs）是一类调控翻译的非编码小分子RNA。它们通常在3位非翻译区与mRNA结合，以抑制翻译或使mRNA不稳定。miRNA在包括突触的结构和功能在内的多种神经过程中发挥作用。尸检研究表明，DLPFC中的miRNAs在精神分裂症中发生了改变。miRNA可能参与了DLPFC的神经成熟和突触发生，并且miRNA的改变可能有助于精神分裂症的发展。因此，描述精神分裂症中改变的miRNAs的功能，可以为精神分裂症的分子机制提供见解。 我们先前使用下一代测序分析了精神分裂症患者死后DLPFC中的miRNA表达。在本报告期间，我们研究了在人DLPFC中差异表达的miRNA的层状和细胞类型分布模式及其在人诱导多能干细胞（iPSC）衍生的多巴胺能神经元中的功能。我们分析了改变的miRNA表达对这些神经元的基本生物物理特性、微型和诱发的突触反应以及突触数量的影响。

Numerous studies have shown that the brains of people with schizophrenia have anomalous gene expression which may arise from dysregulation of gene expression. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translation. They bind to mRNAs, usually at the 3 untranslated region, to suppress translation or destabilize mRNAs. miRNAs play a role in a variety of neuronal processes including the structure and function of synapses. Postmortem studies show that miRNAs in the DLPFC are altered in schizophrenia. It is possible that miRNAs are involved in neural maturation and synaptogenesis of the DLPFC and that miRNA alterations may contribute to the development of schizophrenia. Characterizing the functions of miRNAs altered in schizophrenia, therefore, may provide insights into the molecular mechanism of schizophrenia. We previously analyzed miRNA expression using next-generation sequencing in the postmortem DLPFC of individuals affected with schizophrenia. During this reporting period, we examined the laminar and cell-type distribution patterns of a miRNA differentially expressed in the human DLPFC and its function in human induced pluripotent stem cell (iPSC)-derived glutamatergic neurons. We analyzed the effect of altered miRNA expression on the basic biophysical properties, miniature and evoked synaptic responses, and synapse number in these neurons.