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Research Paper. MicroRNA-137 regulates a glucocorticoid receptordependent signalling network: implications for the etiology of schizophrenia.
- Source :
-
Journal of Psychiatry & Neuroscience . Sep2014, Vol. 39 Issue 5, p312-320. 9p. 1 Diagram, 4 Charts. - Publication Year :
- 2014
-
Abstract
- BACKGROUND: Schizophrenia is a highly heritable neurodevelopmental disorder. A genetic variant of microRNA-137 (miR-137) has yielded significant genome-wide association with schizophrenia, suggesting that this miRNA plays a key role in its etiology. Therefore, a molecular network of interacting miR-137 targets may provide insights into the biological processes underlying schizophrenia. METHODS: We first used bioinformatics tools to obtain and analyze predicted human and mouse miR-137 targets. We then determined miR-137 levels in rat barrel cortex after environmental enrichment (EE), a neuronal plasticity model that induces upregulation of several predicted miR-137 targets. Subsequently, expression changes of these predicted targets were examined through loss of miR-137 function experiments in rat cortical neurons. Finally, we conducted bioinformatics and literature analyses to examine the targets that were upregulated upon miR-137 downregulation. RESULTS: Predicted human and mouse miR-137 targets were enriched in neuronal processes, such as axon guidance, neuritogenesis and neurotransmission. The miR-137 levels were significantly downregulated after EE, and we identified 5 novel miR-137 targets through loss of miR-137 function experiments. These targets fit into a glucocorticoid receptor-dependent signalling network that also includes 3 known miR-137 targets with genome-wide significant association with schizophrenia. LIMITATIONS: The bioinformatics analyses involved predicted human and mouse miR-137 targets owing to lack of information on predicted rat miR-137 targets, whereas follow-up experiments were performed with rats. Furthermore, indirect effects in the loss of miR-137 function experiments cannot be excluded. CONCLUSION: We have identified a miR-137-regulated protein network that contributes to our understanding of the molecular basis of schizophrenia and provides clues for future research into psychopharmacological treatments for schizophrenia. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 11804882
- Volume :
- 39
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Psychiatry & Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 98579103
- Full Text :
- https://doi.org/10.1503/jpn.130269