Impact of in vivo chronic blockade of adenosine A_2A receptors on the BDNF-mediated facilitation of LTP

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 A _2A receptor (A_2AR), the antagonists of A_2AR 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 A_2AR antagonist (KW-6002) in the BDNF actions upon hippocampal CA1 LTP. The results showed that chronic blockade of A _2AR 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 A_2AR blocking conditions.