Author(s): Jerónimo-Santos, André ; Fonseca-Gomes, João ; Guimarães, Diogo Andrade ; Tanqueiro, Sara ; Ramalho, Rita Mira ; Ribeiro, Joaquim A. ; Sebastião, Ana M ; Diógenes, Maria José
Date: 2015
Persistent ID: http://hdl.handle.net/10451/51779
Origin: Repositório da Universidade de Lisboa
Subject(s): Adenosine; Brain-derived neurotrophic factor (BDNF); TrkB; Amyloid-β; Calpain; Caspase-3
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.
