Document Detail


Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine.
MedLine Citation:
PMID:  18384819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The excitatory action of brain-derived neurotrophic factor (BDNF) on synaptic transmission is triggered by adenosine A2A receptor activation. Since high-frequency neuronal firing, such as that inducing long-term potentiation (LTP), favours both A2A receptor activation and BDNF effects on transmission, we now evaluated the influence of adenosine on the facilitatory action of BDNF upon CA1 hippocampal LTP. theta-Burst stimulation of the pyramidal inputs induced a significant and persistent increase in field EPSP slopes, and this potentiation was augmented in the presence of BDNF (20 ng/ml), an action prevented by the inhibitor of Trk receptor autophosphorylation, K252a (200 nM). Removal of endogenous extracellular adenosine with adenosine deaminase (ADA, 1 U/ml), as well as the antagonism of adenosine A2A receptors with SCH58261 (100 nM), prevented the excitatory action of BDNF upon LTP. In an adenosine depleted background (with ADA), activation of adenosine A2A receptors (with 10nM CGS21680) restored the facilitatory effect of BDNF on LTP; this was fully prevented by the protein kinase A inhibitor, H-89 (1 microM) and mimicked by the adenylate cyclase activator, forskolin (10 microM). In similar experiments, activation of adenosine inhibitory A1 receptors (with 5 nM CPA) did not affect the facilitatory effect of BDNF. In conclusion, the facilitatory action of BDNF upon hippocampal LTP is critically dependent on the presence of extracellular adenosine and A2A receptor activation through a cAMP/PKA-dependent mechanism. Since extracellular adenosine accumulates upon high-frequency neuronal firing, the present results reveal a key process to allow the influence of BDNF upon synaptic plasticity.
Authors:
B M Fontinha; M J Diógenes; J A Ribeiro; A M Sebastião
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-02-08
Journal Detail:
Title:  Neuropharmacology     Volume:  54     ISSN:  0028-3908     ISO Abbreviation:  Neuropharmacology     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-21     Completed Date:  2008-07-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  924-33     Citation Subset:  IM    
Affiliation:
Institute of Pharmacology and Neurosciences, Faculty of Medicine and Unit of Neurosciences, Institute of Molecular Medicine, University of Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal.
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MeSH Terms
Descriptor/Qualifier:
Adenosine / analogs & derivatives,  pharmacology,  physiology*
Animals
Brain-Derived Neurotrophic Factor / pharmacology*
Carbazoles / pharmacology
Cyclic AMP / physiology
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Data Interpretation, Statistical
Excitatory Postsynaptic Potentials / drug effects
Hippocampus / drug effects,  physiology
Indole Alkaloids / pharmacology
Isoquinolines / pharmacology
Long-Term Potentiation / drug effects*
Male
Neuroprotective Agents / pharmacology
Phenethylamines / pharmacology
Phosphorylation / drug effects
Pyrimidines / pharmacology
Rats
Rats, Wistar
Receptor, Adenosine A2A / agonists,  antagonists & inhibitors,  physiology*
Sulfonamides / pharmacology
Triazoles / pharmacology
Chemical
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 0/Carbazoles; 0/Indole Alkaloids; 0/Isoquinolines; 0/Neuroprotective Agents; 0/Phenethylamines; 0/Pyrimidines; 0/Receptor, Adenosine A2A; 0/SCH 58261; 0/Sulfonamides; 0/Triazoles; 120225-54-9/CGS 21680; 127243-85-0/H 89; 58-61-7/Adenosine; 60-92-4/Cyclic AMP; 97161-97-2/K 252; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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