Brain-derived neurotrophic factor mediates neuroprotection against Aβ-induced toxicity through a mechanism independent on adenosine 2A receptor activation

• Published in: Growth factors (Chur, Switzerland) Vol. 33; no. 4; pp. 298 - 308
• Main Authors: Jerónimo-Santos, André, Fonseca-Gomes, João, Guimarães, Diogo Andrade, Tanqueiro, Sara Ramalho, Ramalho, Rita Mira, Ribeiro, Joaquim Alexandre, Sebastião, Ana Maria, Diógenes, Maria José
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01-01-2015
• Subjects: Adenosine; Amyloid beta-Peptides - toxicity; amyloid-β; Animals; BDNF; Brain-Derived Neurotrophic Factor - pharmacology; calpain; Caspase 3 - metabolism; caspase-3; Cells, Cultured; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, trkB - metabolism; Receptors, Adenosine A2 - metabolism; TrkB; amyloid-β; calpain; Adenosine; TrkB; BDNF; caspase-3
• ISSN: 0897-7194; 1029-2292
• DOI: 10.3109/08977194.2015.1080696

Brain-derived neurotrophic factor (BDNF) promotes neuronal survival through TrkB-FL activation. The activation of adenosine A
2A
receptors (A
2A
R) is essential for most of BDNF-mediated synaptic actions, such as synaptic plasticity, transmission and neurotransmitter release. We now aimed at evaluating the A
2A
R 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
2A
R activation or inhibition. Moreover neither activation nor inhibition of A
2A
R, 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
2A
R.