Inhibition of microRNA 128 promotes excitability of cultured cortical neuronal networks
- K. Melodi McSweeney1,2,
- Ayal B. Gussow1,3,
- Shelton S. Bradrick4,
- Sarah A. Dugger1,5,
- Sahar Gelfman1,
- Quanli Wang1,
- Slavé Petrovski1,6,
- Wayne N. Frankel1,5,
- Michael J. Boland1,7 and
- David B. Goldstein1,5
- 1Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA;
- 2University Program in Genetics and Genomics, Duke University, Durham, North Carolina 27708, USA;
- 3Computational Biology and Bioinformatics, Duke University, Durham, North Carolina 27708, USA;
- 4Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA;
- 5Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA;
- 6Department of Medicine, The University of Melbourne, Austin Health and Royal Melbourne Hospital, Melbourne, Victoria 3052, Australia;
- 7Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA
- Corresponding author: dg2875{at}cumc.columbia.edu
Abstract
Cultured neuronal networks monitored with microelectrode arrays (MEAs) have been used widely to evaluate pharmaceutical compounds for potential neurotoxic effects. A newer application of MEAs has been in the development of in vitro models of neurological disease. Here, we directly evaluated the utility of MEAs to recapitulate in vivo phenotypes of mature microRNA-128 (miR-128) deficiency, which causes fatal seizures in mice. We show that inhibition of miR-128 results in significantly increased neuronal activity in cultured neuronal networks derived from primary mouse cortical neurons. These results support the utility of MEAs in developing in vitro models of neuroexcitability disorders, such as epilepsy, and further suggest that MEAs provide an effective tool for the rapid identification of microRNAs that promote seizures when dysregulated.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.199828.115.
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Freely available online through the Genome Research Open Access option.
- Received September 18, 2015.
- Accepted August 8, 2016.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
