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.
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Science, Budapest, Hungary. karlocai@koki.hu.
authors.forename: Mária R
authors.initials: MR
authors.lastname: Karlócai
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Science, Budapest, Hungary.|Institute of Cognitive Neuroscience and Psychology, Research Institute of Natural Sciences, Hungarian Academy of Science, 1117, Budapest, Hungary.|National Institute of Clinical Neuroscience, Budapest, 1577, Hungary.
authors.forename: Lucia
authors.initials: L
authors.lastname: Wittner
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Science, Budapest, Hungary.|Institute of Cognitive Neuroscience and Psychology, Research Institute of Natural Sciences, Hungarian Academy of Science, 1117, Budapest, Hungary.
authors.forename: Kinga
authors.initials: K
authors.lastname: Tóth
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Science, Budapest, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Maglóczky
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Science, Budapest, Hungary.
authors.forename: Zoja
authors.initials: Z
authors.lastname: Katarova
authors.affiliation: National Institute of Clinical Neuroscience, Budapest, 1577, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Rásonyi
authors.affiliation: National Institute of Clinical Neuroscience, Budapest, 1577, Hungary.
authors.forename: Loránd
authors.initials: L
authors.lastname: Erőss
authors.affiliation: National Institute of Clinical Neuroscience, Budapest, 1577, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Czirják
authors.affiliation: National Institute of Clinical Neuroscience, Budapest, 1577, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Halász
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Science, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.affiliation: Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, 95616, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Payne
authors.affiliation: Department of Biosciences, University of Helsinki, 00014, Helsinki, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaila
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Science, Budapest, Hungary.
authors.forename: Tamás F
authors.initials: TF
authors.lastname: Freund
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D010862:Pilocarpine; D027981:Symporters / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D010862:Pilocarpine; D027981:Symporters; C000606816:SLC12A5 protein, human; D000096922:K Cl- Cotransporters
keywords: GABA; Hippocampus; Human TLE; KCC2; Spinogenesis