Activation of adenosine A2_A receptor up-regulates BDNF expression in rat primary cortical neurons

As a member of neurotrophin family, brain derived neurotrophic factor (BDNF) plays critical roles in neuronal development, differentiation, synaptogenesis, and neural protection from the harmful stimuli. There have been reported that adenosine A2_A receptor subtype is widely distributed in the brain regions, such as hippocampus, striatum, and cortex. Adenosine A2 _A receptor is colocalized with BDNF in brain regions and the functional interaction between A2_A receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that the activation of A2_A receptor modulates BDNF production in rat primary cortical neuron. CGS21680, an adenosine A2_A receptor agonist, induced BDNF expression and release. An antagonist against A2_A receptor, ZM241385, prevented CGS21680-induced increase in BDNF production. A2_A receptor stimulation induced the activation of Akt-GSK-3β signaling pathway and the blockade of the signaling pathway with specific inhibitors abolished the increase in BDNF production, possibly via modulation of ERK1/2-CREB pathway. The physiological roles of A2_A receptor-induced BDNF production was demonstrated by the protection of neurons from the excitotoxicity and increased neurite extension as well as synapse formation from immature and mature neurons. Taken together, activation of A2_A receptor regulates BDNF production in rat cortical neuron, which provides neuro-protective action.