title: Brain-derived neurotrophic factor mediates neuroprotection against Aβ-induced toxicity through a mechanism independent on adenosine 2A receptor activation.
abstract: Brain-derived neurotrophic factor (BDNF) promotes neuronal survival through TrkB-FL activation. The activation of adenosine A2A receptors (A2AR) is essential for most of BDNF-mediated synaptic actions, such as synaptic plasticity, transmission and neurotransmitter release. We now aimed at evaluating the A2AR influence upon BDNF-mediated neuroprotection against Aβ25-35 toxicity in cultured neurons. Results showed that BDNF increases cell survival and reduces the caspase-3 and calpain activation induced by amyloid-β (Aβ) peptide, in a mechanism probably dependent on PLCγ pathway. This BDNF-mediated neuroprotection is not affected by A2AR activation or inhibition. Moreover neither activation nor inhibition of A2AR, per se, significantly influenced Aβ-induced neuronal death on calpain-mediated cleavage of TrkB induced by Aβ. In conclusion, these results suggest that, in opposition to the fast synaptic actions of BDNF, the neuroprotective actions of this neurotrophin against a strong Aβ insult do not require the activation of A2AR.
authors.affiliation: a Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon , Lisbon , Portugal and.|b Instituto de Medicina Molecular, University of Lisbon , Lisbon , Portugal.
authors.forename: André
authors.initials: A
authors.lastname: Jerónimo-Santos
authors.affiliation: a Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon , Lisbon , Portugal and.|b Instituto de Medicina Molecular, University of Lisbon , Lisbon , Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Fonseca-Gomes
authors.affiliation: a Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon , Lisbon , Portugal and.|b Instituto de Medicina Molecular, University of Lisbon , Lisbon , Portugal.
authors.forename: Diogo Andrade
authors.initials: DA
authors.lastname: Guimarães
authors.affiliation: a Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon , Lisbon , Portugal and.|b Instituto de Medicina Molecular, University of Lisbon , Lisbon , Portugal.
authors.forename: Sara Ramalho
authors.initials: SR
authors.lastname: Tanqueiro
authors.affiliation: a Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon , Lisbon , Portugal and.|b Instituto de Medicina Molecular, University of Lisbon , Lisbon , Portugal.
authors.forename: Rita Mira
authors.initials: RM
authors.lastname: Ramalho
authors.affiliation: a Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon , Lisbon , Portugal and.|b Instituto de Medicina Molecular, University of Lisbon , Lisbon , Portugal.
authors.forename: Joaquim Alexandre
authors.initials: JA
authors.lastname: Ribeiro
authors.affiliation: a Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon , Lisbon , Portugal and.|b Instituto de Medicina Molecular, University of Lisbon , Lisbon , Portugal.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Sebastião
authors.affiliation: a Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon , Lisbon , Portugal and.|b Instituto de Medicina Molecular, University of Lisbon , Lisbon , Portugal.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Diógenes
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D043683:Receptors, Adenosine A2 / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D043683:Receptors, Adenosine A2; D020813:Receptor, trkB; D053148:Caspase 3
keywords: Adenosine; BDNF; TrkB; amyloid-β; calpain; caspase-3