title: BDNF is required for seizure-induced but not developmental up-regulation of KCC2 in the neonatal hippocampus.
abstract: A robust increase in the functional expression of the neuronal K-Cl cotransporter KCC2 during CNS development is necessary for the emergence of hyperpolarizing ionotropic GABAergic transmission. BDNF-TrkB signaling has been implicated in the developmental up-regulation of KCC2 and, in mature animals, in fast activity-dependent down-regulation of KCC2 function following seizures and trauma. In contrast to the decrease in KCC2 expression observed in the adult hippocampus following trauma, seizures in the neonate trigger a TrkB-dependent up-regulation of neuronal Cl(-) extrusion capacity associated with enhanced surface expression of KCC2. Here, we show that this effect is transient, and impaired in the hippocampus of Bdnf(-/-) mice. Notably, however, a complete absence of BDNF does not compromise the increase in KCC2 protein or K-Cl transport functionality during neuronal development. Furthermore, we present data indicating that the functional up-regulation of KCC2 by neonatal seizures is temporally limited by calpain activity.
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Martin
authors.initials: M
authors.lastname: Puskarjov
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Faraz
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Khirug
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Sivakumaran
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaila
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: blaesse@uni-muenster.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Blaesse
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D002154:Calpain / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007608:Kainic Acid; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000503:physiopathology*; D013226:Status Epilepticus / Q000503:physiopathology; D027981:Symporters / Q000378:metabolism*; D046509:Tissue Culture Techniques; D015854:Up-Regulation; D000096922:K Cl- Cotransporters
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002154:Calpain; D002712:Chlorides; D007608:Kainic Acid; D027981:Symporters; D000096922:K Cl- Cotransporters
keywords: BDNF; Calpain; KCC2; Neonatal; Seizures; Status epilepticus