BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion
(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)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/record/321293
- author
- organization
- publishing date
- 2002
- 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
- 2007-11-09 08:42:42
- date last changed
- 2018-04-08 03:44:18
@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}, keyword = {neurotrophic factors,chloride homeostasis,depolarization,GABA(A),inhibition,hippocampus}, 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}, volume = {159}, year = {2002}, }