Activation of Adenosine A2A Receptor Up-Regulates BDNF Expression in Rat Primary Cortical Neurons

Abstract

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.

Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A2A receptor-dependent manner: A2A receptor blockade prevents BDNF release and proliferation of microglia

“…In parallel, it is known that A 2A R modulates BDNF levels both in neurons [34] and in native tissue [35]. Since this effect has not yet been reported in microglia, we tested the ability of a supra-maximal and selective concentration (50 nM) of an A 2A R antagonist, SCH58261 [24], to control BDNF levels in the absence and in the presence of LPS.…”

Oroxylin A enhances memory consolidation through the brain-derived neurotrophic factor in mice

“…It has been reported that GABA A receptor agonists suppress the activity of the MAPK pathway (Kalluri and Ticku, 2002;Igaz et al, 2006;Zheng et al, 2007) and that antagonists exert the opposite effect (Zheng et al, 2007;Kim et al, 2012). Moreover, adenosine A2 A receptor activation regulates BDNF production in rat cortical or hippocampal neurons (Diogenes et al, 2004;Jeon et al, 2011a). Taken together, the effect of oroxylin A on BDNF signaling might be mediated via GABA A or adenosine A2 A receptor signaling.…”

Purinergic Signaling and Hippocampal Long-Term Potentiation

“…detected decreased BDNF levels in the hippocampus of A2a receptor deficient mice by ELISA measurements [32]. These findings were supported recently by Jeon et al ., who demonstrated that A2a receptor stimulation increases BDNF expression in cultured rat cortical neurons via the Akt/GSK-3β signaling pathway [33]. …”