title: Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF-mediated facilitation of LTP.
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 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.
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Universidade de Lisboa, Portugal.
authors.forename: André
authors.initials: A
authors.lastname: Jerónimo-Santos
authors.affiliation: Instituto de Medicina Molecular, Universidade de Lisboa, Portugal.
authors.forename: Vânia L
authors.initials: VL
authors.lastname: Batalha
authors.affiliation: PharmaCenter Bonn, Pharmazeutische Chemie I, Pharmazeutisches Institut, University of Bonn, Bonn, Germany.
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.affiliation: PharmaCenter Bonn, Pharmazeutische Chemie I, Pharmazeutisches Institut, University of Bonn, Bonn, Germany; Sultan Qaboos University, Department of Chemistry, Faculty of Science, Muscat, Oman.
authors.forename: Younis
authors.initials: Y
authors.lastname: Baqi
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Universidade de Lisboa, Portugal.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Sebastião
authors.affiliation: Instituto de Medicina Molecular, Universidade de Lisboa, Portugal.
authors.forename: Luisa V
authors.initials: LV
authors.lastname: Lopes
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Universidade de Lisboa, Portugal. Electronic address: diogenes@fm.ul.pt.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Diógenes
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D019208:Brain-Derived Neurotrophic Factor; D011687:Purines; D043705:Receptor, Adenosine A2A; C111599:istradefylline; D020813:Receptor, trkB
keywords: Alzheimer's disease; Istradefylline; KW-6002; TrkB