Format

Send to

Choose Destination
Neuropharmacology. 2015 Jan;88:103-9. doi: 10.1016/j.neuropharm.2014.09.005. Epub 2014 Sep 16.

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

Author information

1
Department of Biosciences and Neuroscience Center, University of Helsinki, FI-00014 Helsinki, Finland.
2
Department of Biosciences and Neuroscience Center, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: blaesse@uni-muenster.de.

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.

KEYWORDS:

BDNF; Calpain; KCC2; Neonatal; Seizures; Status epilepticus

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center