腺苷A2A受体
腺苷
腺苷受体
内科学
内分泌学
腺苷A1受体
受体
CREB1号
腺苷A3受体
抗抑郁药
药理学
化学
医学
奶油
兴奋剂
生物化学
海马体
转录因子
基因
作者
Yinglin Zhao,Handi Zhang,Yinnan Zhang,Florian Zeman,Chongtao Xu
标识
DOI:10.1021/acschemneuro.2c00167
摘要
As neuromodulators, adenosine and its receptors are mediators of sleep–wake regulation. A putative correlation between CREB1 and depression has been predicted in our bioinformatics analyses, and its expression was also predicted to be upregulated in response to sleep deprivation. Therefore, this study aims to elaborate the A1 and A2A adenosine receptors and CREB1-associated mechanism underlying the antidepressant effect of rapid eye movement sleep deprivation (REMSD) in rats with chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors. The modeled rats were injected with adenosine A1 receptor antagonist DPCPX or adenosine A2A receptor antagonist ZM241385 to assess the role of adenosine receptors in depression. In addition, ectopic expression and depletion experiments of CREB1 and YAP1 were also conducted in vivo and in vitro. It was found that REMSD alleviated depressive-like behaviors in CUMS rats, as shown by increased spontaneous activity, sucrose consumption and percentage, and shortened escape latency and immobility duration. Meanwhile, A1 or A2A adenosine receptor antagonists negated the antidepressant effect of REMSD. REMSD enhanced adenosine receptor activation and promoted the phosphorylation of CREB1, thus increasing the expression of CREB1. In addition, the overexpression of CREB1 activated the YAP1/c-Myc axis and consequently alleviated depressive-like behaviors. Collectively, our results provide new mechanistic insights for an understanding of the antidepressant effect of REMSD, which is associated with the activation of adenosine receptors and the CREB1/YAP1/c-Myc axis.
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