Journal article
Inhibition of microRNA 128 promotes excitability of cultured cortical neuronal networks
KM McSweeney, AB Gussow, SS Bradrick, SA Dugger, S Gelfman, Q Wang, S Petrovski, WN Frankel, MJ Boland, DB Goldstein
Genome Research | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT | Published : 2016
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..
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Awarded by National Institute of General Medical Sciences
Funding Acknowledgements
We thank Dr. Edward M. Kennedy and Dr. Bryan Cullen for providing us with the plasmids and generous advice on sponge generation and transduction. We thank Dr. David Henshall and the EpimiRNA consortium (European Union Seventh Framework Programme [FP7/2007-2013] under grant agreement no. 602130) for valuable discussions. We also thank Dr. Xiaodi Yao, Dr. Yi-Fan Lu, and Dr. Brian Krueger for useful discussions in experiment planning and Sam Hofacker for performing some of the experimental recordings. A.B.G. is supported by the National Institute of Neurological Disorders And Stroke of the National Institutes of Health under award number F31NS092362, and S.P. is a National Health and Medical Research Council of Australia (NHMRC; CJ Martin) Early Career Fellow. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The listed funders had no role in design, collection, analysis, or interpretation of data and no role in the drafting of the manuscript.