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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Thomas-crusells, Judith Lahtinen, Hannele Li, Hong Kokaia, Zaal Kaila, Kai Airaksinen, Matti S. Viitanen, Tero Saarma, Mart Nanobashvili, Avtandil Rivera, Claudio Voipio, Juha |
| Description | Author Affiliation: Rivera C ( Department of Biosciences, Division of Animal Physiology, Institute of Biotechnology, University of Helsinki, Finland. rivera@operoni.helsinki.fi) |
| 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 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. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 5 |
| Volume Number | 159 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2002-12-09 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Brain-Derived Neurotrophic Factor Pharmacology Chlorides Metabolism Hippocampus Neurons Receptor, TrkB Symporters Animals Down-Regulation Drug Effects Electrophysiology Cytology Ion Transport Kindling, Neurologic Physiology Kinetics Membrane Potentials Mice Mice, Inbred C57BL Molecular Sequence Data Nerve Growth Factors Organ Culture Techniques Pyramidal Cells RNA, Messenger Rats, Wistar Recombinant Proteins Time Factors Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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