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

Rivera, C ; Li, H ; Thomas-Crusells, J ; Lahtinen, H ; Viitanen, T ; Nanobashvili, Avtandil LU ; Kokaia, Zaal LU ; Airaksinen, MS ; Voipio, J and Kaila, K , et al. (2002) In Journal of Cell Biology 159(5). p.747-752
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
neurotrophic factors, chloride homeostasis, depolarization, GABA(A), inhibition, hippocampus
in
Journal of Cell Biology
volume
159
issue
5
pages
747 - 752
publisher
Rockefeller University Press
external identifiers
  • wos:000179814700003
  • pmid:12473684
  • scopus:0037049553
ISSN
0021-9525
DOI
10.1083/jcb.200209011
language
English
LU publication?
yes
id
3789bf03-50f1-43c9-b9e7-71eb9959941c (old id 321293)
date added to LUP
2016-04-01 12:27:13
date last changed
2020-12-22 03:28:45
@article{3789bf03-50f1-43c9-b9e7-71eb9959941c,
  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.},
  author       = {Rivera, C and Li, H and Thomas-Crusells, J and Lahtinen, H and Viitanen, T and Nanobashvili, Avtandil and Kokaia, Zaal and Airaksinen, MS and Voipio, J and Kaila, K and Saarma, M},
  issn         = {0021-9525},
  language     = {eng},
  number       = {5},
  pages        = {747--752},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Cell Biology},
  title        = {BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion},
  url          = {http://dx.doi.org/10.1083/jcb.200209011},
  doi          = {10.1083/jcb.200209011},
  volume       = {159},
  year         = {2002},
}