BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Pathophysiological activity and various kinds of traumatic insults are known to have deleterious long-term effects on neuronal Cl- regulation, which can lead to a suppression of fast postsynaptic GABAergic responses. Brain-derived neurotrophic factor (BDNF) increases neuronal excitability through a conjunction of mechanisms that include regulation of the efficacy of GABAergic transmission. Here, we show that exposure of rat hippocampal slice cultures and acute slices to exogenous BDNF or neurotrophin-4 produces a TrkB-mediated fall in the neuron-specific K+-Cl- cotransporter KCC2 mRNA and protein, as well as a consequent impairment in neuronal Cl- extrusion capacity. After kindling-induced seizures in vivo, the expression of KCC2 is down-regulated in the mouse hippocampus with a spatio-temporal profile complementary to the up-regulation of TrkB and BDNF. The present data demonstrate a novel mechanism whereby BDNF/TrkB signaling suppresses chloride-dependent fast GABAergic inhibition, which most likely contributes to the well-known role of TrkB-activated signaling cascades in the induction and establishment of epileptic activity.

Detaljer

Författare
  • C Rivera
  • H Li
  • J Thomas-Crusells
  • H Lahtinen
  • T Viitanen
  • Avtandil Nanobashvili
  • Zaal Kokaia
  • MS Airaksinen
  • J Voipio
  • K Kaila
  • M Saarma
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi

Nyckelord

Originalspråkengelska
Sidor (från-till)747-752
TidskriftJournal of Cell Biology
Volym159
Utgåva nummer5
StatusPublished - 2002
PublikationskategoriForskning
Peer review utfördJa