Modulation of brain-derived neurotrophic factor (BDNF) actions in the nervous system by adenosine A(2A) receptors and the role of lipid rafts.
In this paper we review some novel aspects related to the way adenosine A(2A) receptors (A(2A)R) 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 A(2A)Rs are required for most of the synaptic actions of BDNF. In some cases, where A(2A)Rs are constitutively activated (e.g. by endogenous extracellular adenosine), the need for A(2A)R activation for the maintenance of the synaptic influences of BDNF can be envisaged from the loss of BDNF effects upon blockade of adenosine A(2A)Rs 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 A(2A)Rs (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 A(2A)Rs 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".
Sebastião
Ana M
AM
Institute of Pharmacology and Neurosciences, University of Lisbon, Lisbon, Portugal.
Assaife-Lopes
Natália
N
Diógenes
Maria J
MJ
Vaz
Sandra H
SH
Ribeiro
Joaquim A
JA
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D009435:Synaptic Transmission
D019208:Brain-Derived Neurotrophic Factor; D043705:Receptor, Adenosine A2A