Cerebral ischemia mainly manifests as decreased expression of A1R and increased expression of A2AR, and the effect of inhibition mediated by A1R is weakened and the effect of excitation mediated by A2AR is enhanced.80 Similar mechanisms exist in AD, depression, and epilepsy.81 Therefore, adenosine receptor homeostasis in the brain is the key to the treatments of these diseases. This evidence concerns the gene ADORA2A and major depressive disorder.