The incidence of brain diseases increases with aging, but the biological basis of brain aging is still poorly explored. Synaptic dysfunction occurs at the onset of brain diseases and synaptic neuromodulation systems, such as adenosine A 2A receptors (A 2A R), are necessary and sufficient to trigger brain dysfunction. Since A 2A R are upregulated upon aging, we compared wild-type and A 2A R global knockout mice to test if brain...

The adenosine modulation system is mostly composed by inhibitory A 1 receptors (A 1 R) and the less abundant facilitatory A 2A receptors (A 2A R), the latter selectively engaged at high frequency stimulation associated with synaptic plasticity processes in the hippocampus. A 2A R are activated by adenosine originated from extracellular ATP through ecto-5’-nucleotidase or CD73-mediated catabolism. Using hippocampal synaptosomes...