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

National Institute Of Mental Health

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Abstract

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.