Linked Life Data

12514234

Source:http://linkedlifedata.com/resource/pubmed/id/12514234

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-1-6
pubmed:abstractText
Recent studies have indicated that exogenously administered neurotrophins produce antidepressant-like behavioral effects. We have here investigated the role of endogenous brain-derived neurotrophic factor (BDNF) and its receptor trkB in the mechanism of action of antidepressant drugs. We found that trkB.T1-overexpressing transgenic mice, which show reduced trkB activation in brain, as well as heterozygous BDNF null (BDNF(+/)-) mice, were resistant to the effects of antidepressants in the forced swim test, indicating that normal trkB signaling is required for the behavioral effects typically produced by antidepressants. In contrast, neurotrophin-3(+/)- mice showed a normal behavioral response to antidepressants. Furthermore, acute as well as chronic antidepressant treatment induced autophosphorylation and activation of trkB in cerebral cortex, particularly in the prefrontal and anterior cingulate cortex and hippocampus. Tyrosines in the trkB autophosphorylation site were phosphorylated in response to antidepressants, but phosphorylation of the shc binding site was not observed. Nevertheless, phosphorylation of cAMP response element-binding protein was increased by antidepressants in the prefrontal cortex concomitantly with trkB phosphorylation and this response was reduced in trkB.T1-overexpressing mice. Our data suggest that antidepressants acutely increase trkB signaling in a BDNF-dependent manner in cerebral cortex and that this signaling is required for the behavioral effects typical of antidepressant drugs. Neurotrophin signaling increased by antidepressants may induce formation and stabilization of synaptic connectivity, which gradually leads to the clinical antidepressive effects and mood recovery.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
349-57
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12514234-Animals, pubmed-meshheading:12514234-Antidepressive Agents, pubmed-meshheading:12514234-Behavior, Animal, pubmed-meshheading:12514234-Brain-Derived Neurotrophic Factor, pubmed-meshheading:12514234-Cerebral Cortex, pubmed-meshheading:12514234-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:12514234-Female, pubmed-meshheading:12514234-Fluoxetine, pubmed-meshheading:12514234-Imipramine, pubmed-meshheading:12514234-Kinetics, pubmed-meshheading:12514234-Male, pubmed-meshheading:12514234-Mice, pubmed-meshheading:12514234-Mice, Transgenic, pubmed-meshheading:12514234-Neurons, pubmed-meshheading:12514234-Neurotrophin 3, pubmed-meshheading:12514234-Phosphorylation, pubmed-meshheading:12514234-Prefrontal Cortex, pubmed-meshheading:12514234-Receptor, trkB, pubmed-meshheading:12514234-Signal Transduction
pubmed:year
2003
pubmed:articleTitle
Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects.
pubmed:affiliation
Department of Neurobiology, A. I. Virtanen Institute, University of Kuopio, 70211 Kuopio, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't