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

doi:10.3969/j.issn.1673-5374.2013.06.010

Abstract

Abstract:

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.

Key words: neural regeneration, brain injury, mesial temporal lobe epilepsy, hippocampal sclerosis, sodium-potassium chloride cotransporter 1, potassium chloride cotransporter 2, gamma-aminobutyric acid, chloride ion, dentate gyrus, CA2 region, human, grants-supported paper, photographs-containing paper, neuroregeneration

Xiaodong Cai, Libai Yang, Jueqian Zhou, Dan Zhu, Qiang Guo, Ziyi Chen, Shuda Chen, Liemin Zhou. Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients[J]. Neural Regeneration Research, 2013, 8(6): 561-568.

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