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3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway

BACKGROUND: The development of rapid and safe antidepressants for the treatment of major depression is in urgent demand. Converging evidence suggests that glutamatergic signaling seems to play important roles in the pathophysiology of depression. METHODS: We studied the antidepressant effects of 3(’...

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Autores principales: Li, Bai, Hou, Yangyang, Zhu, Ming, Bao, Hongkun, Nie, Jun, Zhang, Grace Y., Shan, Liping, Yao, Yao, Du, Kai, Yang, Hongju, Li, Meizhang, Zheng, Bingrong, Xu, Xiufeng, Xiao, Chunjie, Du, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851261/
https://www.ncbi.nlm.nih.gov/pubmed/26443809
http://dx.doi.org/10.1093/ijnp/pyv112
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author Li, Bai
Hou, Yangyang
Zhu, Ming
Bao, Hongkun
Nie, Jun
Zhang, Grace Y.
Shan, Liping
Yao, Yao
Du, Kai
Yang, Hongju
Li, Meizhang
Zheng, Bingrong
Xu, Xiufeng
Xiao, Chunjie
Du, Jing
author_facet Li, Bai
Hou, Yangyang
Zhu, Ming
Bao, Hongkun
Nie, Jun
Zhang, Grace Y.
Shan, Liping
Yao, Yao
Du, Kai
Yang, Hongju
Li, Meizhang
Zheng, Bingrong
Xu, Xiufeng
Xiao, Chunjie
Du, Jing
author_sort Li, Bai
collection PubMed
description BACKGROUND: The development of rapid and safe antidepressants for the treatment of major depression is in urgent demand. Converging evidence suggests that glutamatergic signaling seems to play important roles in the pathophysiology of depression. METHODS: We studied the antidepressant effects of 3(’)-deoxyadenosine (3’-dA, Cordycepin) and the critical role of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in male CD-1 mice via behavioral and biochemical experiments. After 3’-dA treatment, the phosphorylation and synaptic localization of the AMPA receptors GluR1 and GluR2 were determined in the prefrontal cortex (PFC) and hippocampus (HIP). The traditional antidepressant imipramine was applied as a positive control. RESULTS: We found that an injection of 3’-dA led to a rapid and robust antidepressant effect, which was significantly faster and stronger than imipramine, after 45min in tail suspension and forced swim tests. This antidepressant effect remained after 5 days of treatment with 3’-dA. Unlike the psycho-stimulants, 3’-dA did not show a hyperactive effect in the open field test. After 45min or 5 days of treatment, 3’-dA enhanced GluR1 S845 phosphorylation in both the PFC and HIP. In addition, after 45min of treatment, 3’-dA significantly up-regulated GluR1 S845 phosphorylation and GluR1, but not GluR2 levels, at the synapses in the PFC. After 5 days of treatment, 3’-dA significantly enhanced GluR1 S845 phosphorylation and GluR1, but not GluR2, at the synapses in the PFC and HIP. Moreover, the AMPA-specific antagonist GYKI 52466 was able to block the rapid antidepressant effects of 3’-dA. CONCLUSION: This study identified 3’-dA as a novel rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the prefrontal AMPA receptor signaling pathway.
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spelling pubmed-48512612016-05-02 3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway Li, Bai Hou, Yangyang Zhu, Ming Bao, Hongkun Nie, Jun Zhang, Grace Y. Shan, Liping Yao, Yao Du, Kai Yang, Hongju Li, Meizhang Zheng, Bingrong Xu, Xiufeng Xiao, Chunjie Du, Jing Int J Neuropsychopharmacol Research Article BACKGROUND: The development of rapid and safe antidepressants for the treatment of major depression is in urgent demand. Converging evidence suggests that glutamatergic signaling seems to play important roles in the pathophysiology of depression. METHODS: We studied the antidepressant effects of 3(’)-deoxyadenosine (3’-dA, Cordycepin) and the critical role of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in male CD-1 mice via behavioral and biochemical experiments. After 3’-dA treatment, the phosphorylation and synaptic localization of the AMPA receptors GluR1 and GluR2 were determined in the prefrontal cortex (PFC) and hippocampus (HIP). The traditional antidepressant imipramine was applied as a positive control. RESULTS: We found that an injection of 3’-dA led to a rapid and robust antidepressant effect, which was significantly faster and stronger than imipramine, after 45min in tail suspension and forced swim tests. This antidepressant effect remained after 5 days of treatment with 3’-dA. Unlike the psycho-stimulants, 3’-dA did not show a hyperactive effect in the open field test. After 45min or 5 days of treatment, 3’-dA enhanced GluR1 S845 phosphorylation in both the PFC and HIP. In addition, after 45min of treatment, 3’-dA significantly up-regulated GluR1 S845 phosphorylation and GluR1, but not GluR2 levels, at the synapses in the PFC. After 5 days of treatment, 3’-dA significantly enhanced GluR1 S845 phosphorylation and GluR1, but not GluR2, at the synapses in the PFC and HIP. Moreover, the AMPA-specific antagonist GYKI 52466 was able to block the rapid antidepressant effects of 3’-dA. CONCLUSION: This study identified 3’-dA as a novel rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the prefrontal AMPA receptor signaling pathway. Oxford University Press 2015-10-06 /pmc/articles/PMC4851261/ /pubmed/26443809 http://dx.doi.org/10.1093/ijnp/pyv112 Text en © The Author 2015. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Li, Bai
Hou, Yangyang
Zhu, Ming
Bao, Hongkun
Nie, Jun
Zhang, Grace Y.
Shan, Liping
Yao, Yao
Du, Kai
Yang, Hongju
Li, Meizhang
Zheng, Bingrong
Xu, Xiufeng
Xiao, Chunjie
Du, Jing
3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway
title 3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway
title_full 3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway
title_fullStr 3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway
title_full_unstemmed 3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway
title_short 3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway
title_sort 3’-deoxyadenosine (cordycepin) produces a rapid and robust antidepressant effect via enhancing prefrontal ampa receptor signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851261/
https://www.ncbi.nlm.nih.gov/pubmed/26443809
http://dx.doi.org/10.1093/ijnp/pyv112
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