title: Inhibition of microRNA 128 promotes excitability of cultured cortical neuronal networks.
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.
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA; University Program in Genetics and Genomics, Duke University, Durham, North Carolina 27708, USA.
authors: K Melodi
authors: KM
authors: McSweeney
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA; Computational Biology and Bioinformatics, Duke University, Durham, North Carolina 27708, USA.
authors: Ayal B
authors: AB
authors: Gussow
authors: Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors: Shelton S
authors: SS
authors: Bradrick
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA; Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA.
authors: Sarah A
authors: SA
authors: Dugger
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA.
authors: Sahar
authors: S
authors: Gelfman
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA.
authors: Quanli
authors: Q
authors: Wang
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA; Department of Medicine, The University of Melbourne, Austin Health and Royal Melbourne Hospital, Melbourne, Victoria 3052, Australia.
authors: Slavé
authors: S
authors: Petrovski
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA; Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA.
authors: Wayne N
authors: WN
authors: Frankel
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA; Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA.
authors: Michael J
authors: MJ
authors: Boland
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, New York 10032, USA; Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA.
authors: David B
authors: DB
authors: Goldstein
mesh_terms: D000200:Action Potentials; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods*; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D035683:MicroRNAs; C550324:Mirn128 microRNA, mouse