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 A_2A receptors (A_2AR) is essential for most of BDNF-mediated synaptic actions, such as synaptic plasticity, transmission and neurotransmitter release. We now aimed at evaluating the A_2AR influence upon BDNF-mediated neuroprotection against Aβ_25–35 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 A_2AR activation or inhibition. Moreover neither activation nor inhibition of A_2AR, 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 A_2AR.

• Adenosine
• amyloid-β
• BDNF
• TrkB
• calpain
• caspase-3

Acknowledgements

We thank Regeneron for the gift of brain-derived neurotrophic factor.

Declaration of interest

None of the authors has any financial interest in this manuscript nor do we foresee any potential conflict of interests. The work was supported by Fundação para a Ciência e a Tecnologia (FCT) and Gabinete de Apoio à Investigação Científica, Tecnológica e Inovação (GAPIC), Faculty of Medicine of Lisbon, University of Lisbon, Portugal—16th Programme for Education and Science. AJS and RMR were supported by FCT (AJS: SFRH/BD/62828/2009; RMR: SFRH/BPD/94474/2013).