title: Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients.
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.
authors.affiliation: Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Libai
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Jueqian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Guangdong 999 Brain Hospital, Guangzhou 510510, Guangdong Province, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Guangdong 999 Brain Hospital, Guangzhou 510510, Guangdong Province, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Shuda
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Liemin
authors.initials: L
authors.lastname: Zhou
keywords: CA2 region; brain injury; chloride ion; dentate gyrus; gamma-aminobutyric acid; grants-supported paper; hippocampal sclerosis; human; mesial temporal lobe epilepsy; neural regeneration; neuroregeneration; photographs-containing paper; potassium chloride cotransporter 2; sodium-potassium chloride cotransporter 1