Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF-mediated facilitation of LTP

Brain-derived neurotrophic factor (BDNF) through the activation of its receptor (TrkB-FL) exert well-described neuroprotective effects playing a major role in hippocampal synaptic transmission and plasticity such as long-term potentiation (LTP), a molecular surrogate for learning and memory. Impairm...

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Published in:Neuropharmacology 2014-08, Vol.83, p.99-106
Main Authors: Jerónimo-Santos, André, Batalha, Vânia L., Müller, Christa E., Baqi, Younis, Sebastião, Ana Maria, Lopes, Luisa V., Diógenes, Maria José
Format: Article
Language:English
Subjects:
Adenosine A2 Receptor Antagonists - pharmacology
Alzheimer's disease
Animals
Brain-Derived Neurotrophic Factor - metabolism
CA1 Region, Hippocampal - drug effects
CA1 Region, Hippocampal - metabolism
Istradefylline
KW-6002
Long-Term Potentiation - drug effects
Male
Purines - pharmacology
Rats
Rats, Wistar
Receptor, Adenosine A2A - metabolism
Receptor, trkB - metabolism
TrkB
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Summary:Brain-derived neurotrophic factor (BDNF) through the activation of its receptor (TrkB-FL) exert well-described neuroprotective effects playing a major role in hippocampal synaptic transmission and plasticity such as long-term potentiation (LTP), a molecular surrogate for learning and memory. Impairments in BDNF signalling have been associated to several neurodegenerative disorders such as Alzheimer's disease (AD). Therefore, the reestablishment of BDNF actions is considered a promising strategy for AD treatment. While, most of BDNF synaptic actions, namely on LTP, require the activation of adenosine A2A receptor (A2AR), the antagonists of A2AR have been proven to prevent AD induced deficits in different animal models. Therefore in this work we aimed to evaluate the impact of a chronic in vivo oral administration of an A2AR antagonist (KW-6002) in the BDNF actions upon hippocampal CA1 LTP. The results showed that chronic blockade of A2AR in male Wistar rats inhibits the facilitatory action of BDNF upon LTP on hippocampal CA1 area and decreases both mRNA and protein levels of the TrkB-FL receptor in hippocampus. These findings imply that BDNF signalling may be affected in chronic A2AR blocking conditions. •Chronic in-vivo blockade of A2AR abolishes BDNF effects upon hippocampal CA1 LTP.•Activation of A2AR after chronic blockade does not restore BDNF effects upon LTP.•Chronic blockade of A2AR reduces mRNA and protein levels of TrkB-FL receptor.
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2014.04.006