RT Journal Article
SR Electronic
T1 MicroRNA-137 regulates a glucocorticoid receptor–dependent signalling network: implications for the etiology of schizophrenia
JF Journal of Psychiatry and Neuroscience
JO J Psychiatry Neurosci
FD Canadian Medical Association
SP 312
OP 320
DO 10.1503/jpn.130269
VO 39
IS 5
A1 Astrid Vallès
A1 Gerard J.M. Martens
A1 Peter De Weerd
A1 Geert Poelmans
A1 Armaz Aschrafi
YR 2014
UL http://jpn.ca/content/39/5/312.abstract
AB 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 psycho-pharmacological treatments for schizophrenia.