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

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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 A2A receptor subtype is widely distributed in the brain regions, such as hippocampus, striatum, and cortex. Adenosine A2A receptor is colocalized with BDNF in brain regions and the functional interaction between A2A receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that the activation of A2A receptor modulates BDNF production in rat primary cortical neuron. CGS21680, an adenosine A2A receptor agonist, induced BDNF expression and release. An antagonist against A2A receptor, ZM241385, prevented CGS21680-induced increase in BDNF production. A2A 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 A2A 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 A2A receptor regulates BDNF production in rat cortical neuron, which provides neuro-protective action.

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Acknowledgments

This work was supported by WCU (World Class University) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (R33-2008-000-10090-0).

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Authors and Affiliations

  1. Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea

    Se Jin Jeon, So Young Rhee & Kwang Ho Ko

  2. Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyunghee University, Seoul, 130-701, Republic of Korea

    Jong Hoon Ryu

  3. Department of Pharmacy, Sahmyook University, Seoul, 139-742, Korea

    Jae Hoon Cheong

  4. Neuroscience Research Center, Institute for Biomedical Sciences and Technology, and School of Medicine, Konkuk University, Seoul, Korea

    Se Jin Jeon, So Young Rhee, Kyungja Kwon, Sung-IL Yang, Seung Hwa Park, Jongmin Lee, Hahn Young Kim, Seol-Heui Han & Chan Young Shin

  5. Department of Pharmacology, School of Medicine, Konkuk University, 1 Hwayang-Dong, Gwangjin-Gu, Seoul, 143-701, Korea

    Chan Young Shin

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  1. Se Jin Jeon
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Correspondence to Chan Young Shin.

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Jeon, S.J., Rhee, S.Y., Ryu, J.H. et al. Activation of Adenosine A2A Receptor Up-Regulates BDNF Expression in Rat Primary Cortical Neurons. Neurochem Res 36, 2259–2269 (2011). https://doi.org/10.1007/s11064-011-0550-y

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  • DOI: https://doi.org/10.1007/s11064-011-0550-y

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