MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy

Honghua Zheng, Rong Tang, Yi Yao, Zhilin Ji, Yuanyuan Cao, Zhaoji Liu, Feng Peng, Wenjie Wang, Dan Can, Huiqin Xing, Guojun Bu, Huaxi Xu, Yun wu Zhang, Weihong Zheng

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Emerging evidence indicates that certain microRNAs (miRNAs) play important roles in epileptogenesis. MiR-219 is a brain-specific miRNA and has been shown to negatively regulate the function of N-methyl-d-aspartate (NMDA) receptors by targeting Ca2+/calmodulin-dependent protein kinase II (CaMKII)γ. Herein, we found that the level of miR-219 was decreased in both the kainic acid (KA)-induced epilepsy model and in cerebrospinal fluid specimens of epilepsy patients. Importantly, silencing of miR-219 by its antagomir in vivo resulted in seizure behaviors, abnormal cortical electroencephalogram (EEG) recordings in the form of high-amplitude and high-frequency discharges, and increased levels of CaMKIIγ and an NMDA receptor component, NR1, in a pattern similar to that found in KA-treated mice. Moreover, treatments with the miR-219 agomir in vivo alleviated seizures, abnormal EEG recordings, and decreased levels of CaMKIIγ and NR1 in KA-treated mice. Furthermore, treatment with MK-801, an antagonist of NMDA receptors, significantly alleviated abnormal EEG recordings induced by miR-219 antagomir. Together, these results demonstrate that miR-219 plays a crucial role in suppressing seizure formation in experimental models of epilepsy through modulating the CaMKII/NMDA receptor pathway and that miR-219 supplement may be a potential anabolic strategy for ameliorating epilepsy.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalMolecular Neurobiology
Volume53
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • CaMKIIγ
  • Epilepsy
  • Kainic acid
  • MiR-219
  • NMDA receptor

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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    Zheng, H., Tang, R., Yao, Y., Ji, Z., Cao, Y., Liu, Z., Peng, F., Wang, W., Can, D., Xing, H., Bu, G., Xu, H., Zhang, Y. W., & Zheng, W. (2016). MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy. Molecular Neurobiology, 53(1), 1-7. https://doi.org/10.1007/s12035-014-8981-5