Modulation of brain-derived neurotrophic factor (BDNF) actions in the nervous system by adenosine A2A receptors and the role of lipid rafts

In this paper we review some novel aspects related to the way adenosine A2A receptors (A2AR) modulate the action of BDNF or its high-affinity receptors, the TrkB receptors, on synaptic transmission and plasticity, as well as upon cholinergic currents and GABA transporters. Evidence has been accumulating that adenosine A2ARs are required for most of the synaptic actions of BDNF. In some cases, where A2ARs are constitutively activated (e.g. by endogenous extracellular adenosine), the need for A2AR activation for the maintenance of the synaptic influences of BDNF can be envisaged from the loss of BDNF effects upon blockade of adenosine A2ARs or upon removal of extracellular adenosine with adenosine deaminase. In some other cases, it is necessary to enhance extracellular adenosine levels (e.g. depolarization) or to further activate A2ARs (e.g. with selective agonists) to trigger a BDNF neuromodulatory role at the synapses. Age- and cell-dependent differences may determine the above two possibilities, but in all cases it is quite clear that there is close interplay between adenosine A2ARs and BDNF TrkB receptors at synapses. The role of lipid rafts in this cross-talk will be discussed. This article is part of a Special Issue entitled: “Adenosine Receptors”.