PMID- 12473684
OWN - NLM
STAT- MEDLINE
DCOM- 20030123
LR  - 20231213
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 159
IP  - 5
DP  - 2002 Dec 9
TI  - BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and 
      impairs neuronal Cl- extrusion.
PG  - 747-52
AB  - 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 spatiotemporal 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.
FAU - Rivera, Claudio
AU  - Rivera C
AD  - Department of Biosciences, Division of Animal Physiology, Institute of 
      Biotechnology, University of Helsinki, Finland. rivera@operoni.helsinki.fi
FAU - Li, Hong
AU  - Li H
FAU - Thomas-Crusells, Judith
AU  - Thomas-Crusells J
FAU - Lahtinen, Hannele
AU  - Lahtinen H
FAU - Viitanen, Tero
AU  - Viitanen T
FAU - Nanobashvili, Avtandil
AU  - Nanobashvili A
FAU - Kokaia, Zaal
AU  - Kokaia Z
FAU - Airaksinen, Matti S
AU  - Airaksinen MS
FAU - Voipio, Juha
AU  - Voipio J
FAU - Kaila, Kai
AU  - Kaila K
FAU - Saarma, Mart
AU  - Saarma M
LA  - eng
SI  - GENBANK/AA982489
SI  - GENBANK/M61178
SI  - GENBANK/X55573
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20021209
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chlorides)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Symporters)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Chlorides/*metabolism
MH  - Down-Regulation/drug effects
MH  - Electrophysiology
MH  - Hippocampus/cytology/*metabolism
MH  - Ion Transport
MH  - Kindling, Neurologic/drug effects/physiology
MH  - Kinetics
MH  - Male
MH  - Membrane Potentials/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Nerve Growth Factors/pharmacology
MH  - Neurons/drug effects/*metabolism
MH  - Organ Culture Techniques
MH  - Pyramidal Cells/cytology/drug effects/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/drug effects/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Symporters/*metabolism
MH  - Time Factors
MH  - K Cl- Cotransporters
PMC - PMC2173387
EDAT- 2002/12/11 04:00
MHDA- 2003/01/24 04:00
PMCR- 2003/06/09
CRDT- 2002/12/11 04:00
PHST- 2002/12/11 04:00 [pubmed]
PHST- 2003/01/24 04:00 [medline]
PHST- 2002/12/11 04:00 [entrez]
PHST- 2003/06/09 00:00 [pmc-release]
AID - jcb.200209011 [pii]
AID - 200209011 [pii]
AID - 10.1083/jcb.200209011 [doi]
PST - ppublish
SO  - J Cell Biol. 2002 Dec 9;159(5):747-52. doi: 10.1083/jcb.200209011. Epub 2002 Dec 
      9.