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

Research output: Contribution to journalArticle

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

Fingerprint

Adenosine A2A Receptors
Long-Term Potentiation
Brain-Derived Neurotrophic Factor
trkB Receptor
Alzheimer Disease
Neuronal Plasticity
Neuroprotective Agents
Synaptic Transmission
Neurodegenerative Diseases
Oral Administration
Wistar Rats
Hippocampus
Animal Models
Learning
Messenger RNA

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

Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF-mediated facilitation of LTP. / Jerónimo-Santos, André; Batalha, Vânia L.; Müller, Christa E.; Baqi, Younis; Sebastião, Ana Maria; Lopes, Luisa V.; Diógenes, Maria José.

In: Neuropharmacology, Vol. 83, 2014, p. 99-106.

Research output: Contribution to journalArticle

Jerónimo-Santos, A, Batalha, VL, Müller, CE, Baqi, Y, Sebastião, AM, Lopes, LV & Diógenes, MJ 2014, 'Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF-mediated facilitation of LTP', Neuropharmacology, vol. 83, pp. 99-106. https://doi.org/10.1016/j.neuropharm.2014.04.006
Jerónimo-Santos, André ; Batalha, Vânia L. ; Müller, Christa E. ; Baqi, Younis ; Sebastião, Ana Maria ; Lopes, Luisa V. ; Diógenes, Maria José. / Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF-mediated facilitation of LTP. In: Neuropharmacology. 2014 ; Vol. 83. pp. 99-106.
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