KCC2 downregulation facilitates epileptic seizures

Abstract GABAA receptor-mediated inhibition depends on the maintenance of low level intracellular [Cl−] concentration, which in adult depends on neuron specific K+-Cl− cotransporter-2 (KCC2). Previous studies have shown that KCC2 was downregulated in both epileptic patients and various epileptic ani...

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Autores principales:	Lulan Chen, Li Wan, Zheng Wu, Wanting Ren, Yian Huang, Binbin Qian, Yun Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d6fdb5f799d4b9dbd946c434bb2a123
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spelling	oai:doaj.org-article:5d6fdb5f799d4b9dbd946c434bb2a1232021-12-02T16:06:00ZKCC2 downregulation facilitates epileptic seizures10.1038/s41598-017-00196-72045-2322https://doaj.org/article/5d6fdb5f799d4b9dbd946c434bb2a1232017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00196-7https://doaj.org/toc/2045-2322Abstract GABAA receptor-mediated inhibition depends on the maintenance of low level intracellular [Cl−] concentration, which in adult depends on neuron specific K+-Cl− cotransporter-2 (KCC2). Previous studies have shown that KCC2 was downregulated in both epileptic patients and various epileptic animal models. However, the temporal relationship between KCC2 downregulation and seizure induction is unclear yet. In this study, we explored the temporal relationship and the influence of KCC2 downregulation on seizure induction. Significant downregulation of plasma membrane KCC2 was directly associated with severe (Racine Score III and above) behavioral seizures in vivo, and occurred before epileptiform bursting activities in vitro induced by convulsant. Overexpression of KCC2 using KCC2 plasmid effectively enhanced resistance to convulsant-induced epileptiform bursting activities in vitro. Furthermore, suppression of membrane KCC2 expression, using shRNAKCC2 plasmid in vitro and shRNAKCC2 containing lentivirus in vivo, induced spontaneous epileptiform bursting activities in vitro and Racine III seizure behaviors accompanied by epileptic EEG in vivo. Our findings novelly demonstrated that altered expression of KCC2 is not the consequence of seizure occurrence but likely is the contributing factor.Lulan ChenLi WanZheng WuWanting RenYian HuangBinbin QianYun WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lulan Chen Li Wan Zheng Wu Wanting Ren Yian Huang Binbin Qian Yun Wang KCC2 downregulation facilitates epileptic seizures
description	Abstract GABAA receptor-mediated inhibition depends on the maintenance of low level intracellular [Cl−] concentration, which in adult depends on neuron specific K+-Cl− cotransporter-2 (KCC2). Previous studies have shown that KCC2 was downregulated in both epileptic patients and various epileptic animal models. However, the temporal relationship between KCC2 downregulation and seizure induction is unclear yet. In this study, we explored the temporal relationship and the influence of KCC2 downregulation on seizure induction. Significant downregulation of plasma membrane KCC2 was directly associated with severe (Racine Score III and above) behavioral seizures in vivo, and occurred before epileptiform bursting activities in vitro induced by convulsant. Overexpression of KCC2 using KCC2 plasmid effectively enhanced resistance to convulsant-induced epileptiform bursting activities in vitro. Furthermore, suppression of membrane KCC2 expression, using shRNAKCC2 plasmid in vitro and shRNAKCC2 containing lentivirus in vivo, induced spontaneous epileptiform bursting activities in vitro and Racine III seizure behaviors accompanied by epileptic EEG in vivo. Our findings novelly demonstrated that altered expression of KCC2 is not the consequence of seizure occurrence but likely is the contributing factor.
format	article
author	Lulan Chen Li Wan Zheng Wu Wanting Ren Yian Huang Binbin Qian Yun Wang
author_facet	Lulan Chen Li Wan Zheng Wu Wanting Ren Yian Huang Binbin Qian Yun Wang
author_sort	Lulan Chen
title	KCC2 downregulation facilitates epileptic seizures
title_short	KCC2 downregulation facilitates epileptic seizures
title_full	KCC2 downregulation facilitates epileptic seizures
title_fullStr	KCC2 downregulation facilitates epileptic seizures
title_full_unstemmed	KCC2 downregulation facilitates epileptic seizures
title_sort	kcc2 downregulation facilitates epileptic seizures
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5d6fdb5f799d4b9dbd946c434bb2a123
work_keys_str_mv	AT lulanchen kcc2downregulationfacilitatesepilepticseizures AT liwan kcc2downregulationfacilitatesepilepticseizures AT zhengwu kcc2downregulationfacilitatesepilepticseizures AT wantingren kcc2downregulationfacilitatesepilepticseizures AT yianhuang kcc2downregulationfacilitatesepilepticseizures AT binbinqian kcc2downregulationfacilitatesepilepticseizures AT yunwang kcc2downregulationfacilitatesepilepticseizures
_version_	1718385151965134848

KCC2 downregulation facilitates epileptic seizures

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