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

André Jerónimo-Santos, Vânia L. Batalha, Christa E. Müller, Younis Baqi, Ana Maria Sebastião, Luisa V. Lopes, Maria José Diógenes

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18 Citations (Scopus)

Abstract

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 A 2A 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 A 2AR 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.

Original languageEnglish
Pages (from-to)99-106
Number of pages8
JournalNeuropharmacology
Volume83
DOIs
Publication statusPublished - 2014

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Keywords

  • Alzheimer's disease
  • Istradefylline
  • KW-6002
  • TrkB

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology
  • Medicine(all)

Cite this

Jerónimo-Santos, A., Batalha, V. L., Müller, C. E., Baqi, Y., Sebastião, A. M., Lopes, L. V., & Diógenes, M. J. (2014). Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF-mediated facilitation of LTP. Neuropharmacology, 83, 99-106. https://doi.org/10.1016/j.neuropharm.2014.04.006