Role of Adenosine A_2A Receptors in Modulating Synaptic Functions and Brain Levels of BDNF: a Possible Key Mechanism in the Pathophysiology of Huntington's Disease

Abstract

In the last few years, accumulating evidence has shown the existence of an important cross-talk between adenosine A_2A receptors (A_2ARs) and brain-derived neurotrophic factor (BDNF). Not only are A_2ARs involved in the mechanism of transactivation of BDNF receptor TrkB, they also modulate the effect of BDNF on synaptic transmission, playing a facilitatory and permissive role. The cAMP-PKA pathway, the main transduction system operated by A_2ARs, is involved in such effects. Furthermore, a basal tonus of A_2ARs is required to allow the regulation of BDNF physiological levels in the brain, as demonstrated by the reduced protein levels measured in A_2ARs KO mice. The crucial role of adenosine A_2ARs in the maintenance of synaptic functions and BDNF levels will be reviewed here and discussed in the light of possible implications for Huntington's disease therapy, in which a joint impairment of BDNF and A_2ARs seems to play a pathogenetic role.