Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy

Mária R. Karlócai, Lucia Wittner, Kinga Tóth, Zsófia Maglóczky, Zoja Katarova, György Rásonyi, Loránd Erőss, Sándor Czirják, Péter Halász, Gábor Szabó, John A Payne, Kai Kaila, Tamás F. Freund

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAA receptor-mediated chloride currents. In addition, KCC2 also interacts with the actin cytoskeleton which is critical for dendritic spine morphogenesis, and for the maintenance of glutamatergic synapses and cell volume. Using immunocytochemistry, we examined the cellular and subcellular levels of KCC2 in surgically removed hippocampi of temporal lobe epilepsy (TLE) patients and compared them to control human tissue. We also studied the distribution of KCC2 in a pilocarpine mouse model of epilepsy. An overall increase in KCC2-expression was found in epilepsy and confirmed by Western blots. The cellular and subcellular distributions in control mouse and human samples were largely similar; moreover, changes affecting KCC2-expression were also alike in chronic epileptic human and mouse hippocampi. At the subcellular level, we determined the neuronal elements exhibiting enhanced KCC2 expression. In epileptic tissue, staining became more intense in the immunopositive elements detected in control tissue, and profiles with subthreshold expression of KCC2 in control samples became labelled. Positive interneuron somata and dendrites were more numerous in epileptic hippocampi, despite severe interneuron loss. Whether the elevation of KCC2-expression is ultimately a pro- or anticonvulsive change, or both—behaving differently during ictal and interictal states in a context-dependent manner—remains to be established.

Original languageEnglish (US)
JournalBrain Structure and Function
DOIs
StateAccepted/In press - Oct 1 2015

Fingerprint

Temporal Lobe Epilepsy
Hippocampus
Dendritic Spines
Interneurons
Chlorides
Epilepsy
Pilocarpine
Carisoprodol
GABA-A Receptors
Dendrites
Actin Cytoskeleton
Morphogenesis
Cell Size
Synapses
Homeostasis
Western Blotting
Immunohistochemistry
Stroke
Maintenance
Ions

Keywords

  • GABA
  • Hippocampus
  • Human TLE
  • KCC2
  • Spinogenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Anatomy
  • Histology

Cite this

Karlócai, M. R., Wittner, L., Tóth, K., Maglóczky, Z., Katarova, Z., Rásonyi, G., ... Freund, T. F. (Accepted/In press). Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy. Brain Structure and Function. https://doi.org/10.1007/s00429-015-1122-8

Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy. / Karlócai, Mária R.; Wittner, Lucia; Tóth, Kinga; Maglóczky, Zsófia; Katarova, Zoja; Rásonyi, György; Erőss, Loránd; Czirják, Sándor; Halász, Péter; Szabó, Gábor; Payne, John A; Kaila, Kai; Freund, Tamás F.

In: Brain Structure and Function, 01.10.2015.

Research output: Contribution to journalArticle

Karlócai, MR, Wittner, L, Tóth, K, Maglóczky, Z, Katarova, Z, Rásonyi, G, Erőss, L, Czirják, S, Halász, P, Szabó, G, Payne, JA, Kaila, K & Freund, TF 2015, 'Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy', Brain Structure and Function. https://doi.org/10.1007/s00429-015-1122-8
Karlócai, Mária R. ; Wittner, Lucia ; Tóth, Kinga ; Maglóczky, Zsófia ; Katarova, Zoja ; Rásonyi, György ; Erőss, Loránd ; Czirják, Sándor ; Halász, Péter ; Szabó, Gábor ; Payne, John A ; Kaila, Kai ; Freund, Tamás F. / Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy. In: Brain Structure and Function. 2015.
@article{47907f86a7a54dd59fe8bba495b17af6,
title = "Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy",
abstract = "Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAA receptor-mediated chloride currents. In addition, KCC2 also interacts with the actin cytoskeleton which is critical for dendritic spine morphogenesis, and for the maintenance of glutamatergic synapses and cell volume. Using immunocytochemistry, we examined the cellular and subcellular levels of KCC2 in surgically removed hippocampi of temporal lobe epilepsy (TLE) patients and compared them to control human tissue. We also studied the distribution of KCC2 in a pilocarpine mouse model of epilepsy. An overall increase in KCC2-expression was found in epilepsy and confirmed by Western blots. The cellular and subcellular distributions in control mouse and human samples were largely similar; moreover, changes affecting KCC2-expression were also alike in chronic epileptic human and mouse hippocampi. At the subcellular level, we determined the neuronal elements exhibiting enhanced KCC2 expression. In epileptic tissue, staining became more intense in the immunopositive elements detected in control tissue, and profiles with subthreshold expression of KCC2 in control samples became labelled. Positive interneuron somata and dendrites were more numerous in epileptic hippocampi, despite severe interneuron loss. Whether the elevation of KCC2-expression is ultimately a pro- or anticonvulsive change, or both—behaving differently during ictal and interictal states in a context-dependent manner—remains to be established.",
keywords = "GABA, Hippocampus, Human TLE, KCC2, Spinogenesis",
author = "Karl{\'o}cai, {M{\'a}ria R.} and Lucia Wittner and Kinga T{\'o}th and Zs{\'o}fia Magl{\'o}czky and Zoja Katarova and Gy{\"o}rgy R{\'a}sonyi and Lor{\'a}nd Erőss and S{\'a}ndor Czirj{\'a}k and P{\'e}ter Hal{\'a}sz and G{\'a}bor Szab{\'o} and Payne, {John A} and Kai Kaila and Freund, {Tam{\'a}s F.}",
year = "2015",
month = "10",
day = "1",
doi = "10.1007/s00429-015-1122-8",
language = "English (US)",
journal = "Anatomy and Embryology",
issn = "0177-5154",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy

AU - Karlócai, Mária R.

AU - Wittner, Lucia

AU - Tóth, Kinga

AU - Maglóczky, Zsófia

AU - Katarova, Zoja

AU - Rásonyi, György

AU - Erőss, Loránd

AU - Czirják, Sándor

AU - Halász, Péter

AU - Szabó, Gábor

AU - Payne, John A

AU - Kaila, Kai

AU - Freund, Tamás F.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAA receptor-mediated chloride currents. In addition, KCC2 also interacts with the actin cytoskeleton which is critical for dendritic spine morphogenesis, and for the maintenance of glutamatergic synapses and cell volume. Using immunocytochemistry, we examined the cellular and subcellular levels of KCC2 in surgically removed hippocampi of temporal lobe epilepsy (TLE) patients and compared them to control human tissue. We also studied the distribution of KCC2 in a pilocarpine mouse model of epilepsy. An overall increase in KCC2-expression was found in epilepsy and confirmed by Western blots. The cellular and subcellular distributions in control mouse and human samples were largely similar; moreover, changes affecting KCC2-expression were also alike in chronic epileptic human and mouse hippocampi. At the subcellular level, we determined the neuronal elements exhibiting enhanced KCC2 expression. In epileptic tissue, staining became more intense in the immunopositive elements detected in control tissue, and profiles with subthreshold expression of KCC2 in control samples became labelled. Positive interneuron somata and dendrites were more numerous in epileptic hippocampi, despite severe interneuron loss. Whether the elevation of KCC2-expression is ultimately a pro- or anticonvulsive change, or both—behaving differently during ictal and interictal states in a context-dependent manner—remains to be established.

AB - Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAA receptor-mediated chloride currents. In addition, KCC2 also interacts with the actin cytoskeleton which is critical for dendritic spine morphogenesis, and for the maintenance of glutamatergic synapses and cell volume. Using immunocytochemistry, we examined the cellular and subcellular levels of KCC2 in surgically removed hippocampi of temporal lobe epilepsy (TLE) patients and compared them to control human tissue. We also studied the distribution of KCC2 in a pilocarpine mouse model of epilepsy. An overall increase in KCC2-expression was found in epilepsy and confirmed by Western blots. The cellular and subcellular distributions in control mouse and human samples were largely similar; moreover, changes affecting KCC2-expression were also alike in chronic epileptic human and mouse hippocampi. At the subcellular level, we determined the neuronal elements exhibiting enhanced KCC2 expression. In epileptic tissue, staining became more intense in the immunopositive elements detected in control tissue, and profiles with subthreshold expression of KCC2 in control samples became labelled. Positive interneuron somata and dendrites were more numerous in epileptic hippocampi, despite severe interneuron loss. Whether the elevation of KCC2-expression is ultimately a pro- or anticonvulsive change, or both—behaving differently during ictal and interictal states in a context-dependent manner—remains to be established.

KW - GABA

KW - Hippocampus

KW - Human TLE

KW - KCC2

KW - Spinogenesis

UR - http://www.scopus.com/inward/record.url?scp=84944524805&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944524805&partnerID=8YFLogxK

U2 - 10.1007/s00429-015-1122-8

DO - 10.1007/s00429-015-1122-8

M3 - Article

C2 - 26427846

AN - SCOPUS:84944524805

JO - Anatomy and Embryology

JF - Anatomy and Embryology

SN - 0177-5154

ER -