BDNF is required for seizure-induced but not developmental up-regulation of KCC2 in the neonatal hippocampus. (January 2015)

• Record Type: Journal Article
• Authors: Puskarjov, Martin; Ahmad, Faraz; Khirug, Stanislav; Sivakumaran, Sudhir; Kaila, Kai; Blaesse, Peter
• Is Part Of: Neuropharmacology. Volume 88(2015)
• Page Start: 103
• Page End: 109
• Publication Date: 2015-01
• Subjects: KCC2 -- BDNF -- Calpain -- Neonatal -- Seizures -- Status epilepticus; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2014.09.005
• Languages: English
• ISSNs: 0028-3908

Abstract

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. This article is part of the Special Issue entitled 'GABAergic Signaling in Health and Disease'. Highlights: BDNF has been implicated in KCC2 up-regulation during neuronal development. Seizures induce age-dependent changes in KCC2 expression and function. We show that developmental up-regulation of KCC2 is unaffected in Bdnf −/− hippocampi. By contrast, lack of BDNF impairs KCC2 activation triggered by neonatal seizures.