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 D Bu, Huaxi Xu, Yun wu Zhang, Weihong Zheng

Research output: Contribution to journalArticle

30 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Kainic Acid
Epilepsy
Seizures
Electroencephalography
MicroRNAs
Dizocilpine Maleate
Cerebrospinal Fluid
Theoretical Models
aspartic acid receptor
Brain
Therapeutics
protein kinase N

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Zheng, H., Tang, R., Yao, Y., Ji, Z., Cao, Y., Liu, Z., ... 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

MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy. / Zheng, Honghua; Tang, Rong; Yao, Yi; Ji, Zhilin; Cao, Yuanyuan; Liu, Zhaoji; Peng, Feng; Wang, Wenjie; Can, Dan; Xing, Huiqin; Bu, Guojun D; Xu, Huaxi; Zhang, Yun wu; Zheng, Weihong.

In: Molecular Neurobiology, Vol. 53, No. 1, 01.01.2016, p. 1-7.

Research output: Contribution to journalArticle

Zheng, H, Tang, R, Yao, Y, Ji, Z, Cao, Y, Liu, Z, Peng, F, Wang, W, Can, D, Xing, H, Bu, GD, Xu, H, Zhang, YW & Zheng, W 2016, 'MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy', Molecular Neurobiology, vol. 53, no. 1, pp. 1-7. https://doi.org/10.1007/s12035-014-8981-5
Zheng, Honghua ; Tang, Rong ; Yao, Yi ; Ji, Zhilin ; Cao, Yuanyuan ; Liu, Zhaoji ; Peng, Feng ; Wang, Wenjie ; Can, Dan ; Xing, Huiqin ; Bu, Guojun D ; Xu, Huaxi ; Zhang, Yun wu ; Zheng, Weihong. / MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy. In: Molecular Neurobiology. 2016 ; Vol. 53, No. 1. pp. 1-7.
@article{5537f137683140b896efb0f2b032fd31,
title = "MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy",
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.",
keywords = "CaMKIIγ, Epilepsy, Kainic acid, MiR-219, NMDA receptor",
author = "Honghua Zheng and Rong Tang and Yi Yao and Zhilin Ji and Yuanyuan Cao and Zhaoji Liu and Feng Peng and Wenjie Wang and Dan Can and Huiqin Xing and Bu, {Guojun D} and Huaxi Xu and Zhang, {Yun wu} and Weihong Zheng",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/s12035-014-8981-5",
language = "English (US)",
volume = "53",
pages = "1--7",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "1",

}

TY - JOUR

T1 - MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy

AU - Zheng, Honghua

AU - Tang, Rong

AU - Yao, Yi

AU - Ji, Zhilin

AU - Cao, Yuanyuan

AU - Liu, Zhaoji

AU - Peng, Feng

AU - Wang, Wenjie

AU - Can, Dan

AU - Xing, Huiqin

AU - Bu, Guojun D

AU - Xu, Huaxi

AU - Zhang, Yun wu

AU - Zheng, Weihong

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - CaMKIIγ

KW - Epilepsy

KW - Kainic acid

KW - MiR-219

KW - NMDA receptor

UR - http://www.scopus.com/inward/record.url?scp=84953354924&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953354924&partnerID=8YFLogxK

U2 - 10.1007/s12035-014-8981-5

DO - 10.1007/s12035-014-8981-5

M3 - Article

C2 - 25394384

AN - SCOPUS:84953354924

VL - 53

SP - 1

EP - 7

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 1

ER -