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

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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.

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Acknowledgments

We thank Zhengli Li for the helpful discussion of the manuscript. This work was supported by grants from the Natural Science Research Foundation of China (81100842, 81225008, 81271895, 81161120496, 91332112, and 91332114) and by the Natural Science Foundation of Fujian Province of China (No. 2012J01418). This work was also supported by the Foundation of Xiamen Science and Technology Bureau (No. 2011S0351).

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, 361005, Fujian Province, China

    Honghua Zheng, Zhilin Ji, Dan Can, Huiqin Xing, Guojun Bu, Huaxi Xu & Yun-wu Zhang

  2. Department of Basic Medicine, Medical College, Xiamen University, Xiamen, 361005, Fujian Province, China

    Honghua Zheng & Zhilin Ji

  3. Department of Neurology, Affiliated Zhongshan Hospital, Xiamen University, Xiamen, 361004, Fujian Province, China

    Rong Tang, Yuanyuan Cao, Zhaoji Liu, Feng Peng, Wenjie Wang & Weihong Zheng

  4. Epilepsy Research Center, Department of Neurosurgery, Affiliated Chenggong Hospital, Xiamen University, Xiamen, 361004, Fujian Province, China

    Yi Yao

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  1. Honghua Zheng
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  2. Rong Tang
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Correspondence to Yun-wu Zhang or Weihong Zheng.

Additional information

Honghua Zheng and Rong Tang contributed equally to this study.

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Zheng, H., Tang, R., Yao, Y. et al. MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy. Mol Neurobiol 53, 1–7 (2016). https://doi.org/10.1007/s12035-014-8981-5

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  • DOI: https://doi.org/10.1007/s12035-014-8981-5

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