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Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients

The Na(+)-K(+)-Cl(-) cotransporter 1 and K(+)-Cl(-) cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the rela...

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Autores principales: Cai, Xiaodong, Yang, Libai, Zhou, Jueqian, Zhu, Dan, Guo, Qiang, Chen, Ziyi, Chen, Shuda, Zhou, Liemin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146056/
https://www.ncbi.nlm.nih.gov/pubmed/25206700
http://dx.doi.org/10.3969/j.issn.1673-5374.2013.06.010
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author Cai, Xiaodong
Yang, Libai
Zhou, Jueqian
Zhu, Dan
Guo, Qiang
Chen, Ziyi
Chen, Shuda
Zhou, Liemin
author_facet Cai, Xiaodong
Yang, Libai
Zhou, Jueqian
Zhu, Dan
Guo, Qiang
Chen, Ziyi
Chen, Shuda
Zhou, Liemin
author_sort Cai, Xiaodong
collection PubMed
description The Na(+)-K(+)-Cl(-) cotransporter 1 and K(+)-Cl(-) cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of Cl(-) homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na(+)-K(+)-Cl(-) cotransporter 1 and K(+)-Cl(-) cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na(+)-K(+)-Cl(-) cotransporter 1 expression and decreased K(+)-Cl(-) cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na(+)-K(+)-Cl(-) cotransporter 1 than for the K(+)-Cl(-) cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na(+)-K(+)-Cl(-) cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.
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spelling pubmed-41460562014-09-09 Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients Cai, Xiaodong Yang, Libai Zhou, Jueqian Zhu, Dan Guo, Qiang Chen, Ziyi Chen, Shuda Zhou, Liemin Neural Regen Res Basic Research in Neural Regeneration The Na(+)-K(+)-Cl(-) cotransporter 1 and K(+)-Cl(-) cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of Cl(-) homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na(+)-K(+)-Cl(-) cotransporter 1 and K(+)-Cl(-) cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na(+)-K(+)-Cl(-) cotransporter 1 expression and decreased K(+)-Cl(-) cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na(+)-K(+)-Cl(-) cotransporter 1 than for the K(+)-Cl(-) cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na(+)-K(+)-Cl(-) cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Medknow Publications & Media Pvt Ltd 2013-02-25 /pmc/articles/PMC4146056/ /pubmed/25206700 http://dx.doi.org/10.3969/j.issn.1673-5374.2013.06.010 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic Research in Neural Regeneration
Cai, Xiaodong
Yang, Libai
Zhou, Jueqian
Zhu, Dan
Guo, Qiang
Chen, Ziyi
Chen, Shuda
Zhou, Liemin
Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients
title Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients
title_full Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients
title_fullStr Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients
title_full_unstemmed Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients
title_short Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients
title_sort anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients
topic Basic Research in Neural Regeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146056/
https://www.ncbi.nlm.nih.gov/pubmed/25206700
http://dx.doi.org/10.3969/j.issn.1673-5374.2013.06.010
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