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

大量研究表明，精神分裂症患者的大脑有异常的基因表达，这可能是由基因表达失调引起的。MicroRNAs （miRNAs）是调节翻译的小的非编码rna。它们通常在3非翻译区与mrna结合，抑制mrna的翻译或破坏mrna的稳定。mirna在多种神经元过程中发挥作用，包括突触的结构和功能。死后研究表明，DLPFC中的mirna在精神分裂症中发生了改变。miRNA可能参与DLPFC的神经成熟和突触发生，miRNA的改变可能导致精神分裂症的发生。因此，表征在精神分裂症中改变的mirna的功能，可能为精神分裂症的分子机制提供见解。

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.