Xiaoyaosan Ameliorates Chronic Restraint Stress-Induced Depression-Like Phenotype by Suppressing A2AR Signaling in the Rat Striatum.
Xiaoyaosan Ameliorates Chronic Restraint Stress-Induced Depression-Like Phenotype by Suppressing A2AR Signaling in the Rat Striatum.
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逍遥散通过抑制大鼠纹状体中的 A2AR 信号传导改善慢性束缚应激诱发的抑郁样表型
DOI：
10.3389/fphar.2022.897436
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发表时间：
2022
影响因子：
5.6
通讯作者：
Chen, Jiaxu
中科院分区：
文献类型：
--
作者：
Zhu, Xiaoxu;Ma, Qingyu;Yang, Furong;Li, Xiaojuan;Liu, Yueyun;Chen, Jianbei;Li, Lan;Chen, Man;Zou, Xiaojuan;Yan, Li;Chen, Jiaxu
抑郁症是一种常见的精神障碍，其特征是悲观和厌世。在我们之前的研究中，我们发现消药散可能具有抗抑郁作用，但其作用机制尚不清楚。多项研究表明，大脑中的腺苷A （2a）受体（A2AR）是治疗抑郁症的关键。本研究旨在探讨XYS对慢性抑制应激大鼠纹状体A2AR信号通路的影响。将96只雄性Sprague-Dawley大鼠随机分为8组（对照组、模型组、阴性对照组、XYS、A2AR拮抗剂、A2AR拮抗剂+ XYS、A2AR激动剂、A2AR激动剂+ XYS）。模型组、XYS组、A2AR拮抗剂组和A2AR拮抗剂+ XYS组大鼠进行CRS，每天3 h。阴性对照组、XYS组、A2AR拮抗剂+ XYS组、A2AR拮抗剂+ XYS组大鼠灌胃XYS煎剂[2.224 g/(kg·d)]。A2AR拮抗剂组和A2AR拮抗剂+ XYS组大鼠给予SCH 58261 [0.05 mg/(kg·d)]， A2AR激动剂和A2AR激动剂+ XYS组大鼠给予CGS 21680 [0.1 mg/(kg·d)]。这些手术连续21天进行。行为学研究包括开放场试验、升高加迷宫试验、蔗糖偏好试验和强迫游泳试验来检测抑郁样表型。然后，观察XYS对CRS-或A2AR激动剂诱导的纹状体亚细胞损伤、小胶质细胞激活和纹状体A2AR信号变化的影响。在这里，我们报道了XYS改善了CRS大鼠的抑郁样表型（如体重减轻以及抑郁和焦虑样行为），并改善了突触存活和生长。此外，XYS还能降低A2AR活性，抑制纹状体小胶质细胞的过度激活。XYS的组织和细胞作用与已知的A2AR拮抗剂相似。综上所述，XYS通过抑制纹状体中的A2AR来减轻CRS大鼠的抑郁。
Depression is a common mental disorder characterized by pessimism and world-weariness. In our previous study, we found that Xiaoyaosan (XYS) could have antidepressive effects, however the underlying mechanisms remain unclear. Several studies have shown that adenosine A (2 A) receptor (A2AR) in the brain is a key point in the treatment of depression. Our present study aimed to investigate the effects of XYS on A2AR signaling in the striatum of rats exposed to chronic restraint stress (CRS). Ninety-six male Sprague–Dawley rats were randomly divided into 8 groups (control, model, negative control, XYS, A2AR antagonist, A2AR antagonist + XYS, A2AR agonist, A2AR agonist + XYS). The rats in the model group, XYS group, A2AR antagonist group and A2AR antagonist + XYS group were subjected to CRS for 3 h a day. The XYS decoction [2.224 g/(kg·d)] was intragastrical administered by oral gavage to the rats in the negative control group, XYS group, A2AR antagonist + XYS group, and A2AR agonist + XYS group. The rats in the A2AR antagonist group and A2AR antagonist + XYS group were treated with SCH 58261 [0.05 mg/(kg·d)], and the rats in the A2AR agonist and A2AR agonist + XYS group were treated with CGS 21680 [0.1 mg/(kg·d)]. These procedures were performed for 21 consecutive days. Behavioral studies including the open field test, elevated plus maze test, sucrose preference test and forced swimming test, were performed to examine depression-like phenotypes. Then, the effects of XYS on CRS- or A2AR agonist-induced striatal subcellular damage, microglial activation and A2AR signaling changes in the striatum were examined. Here, we report that XYS ameliorates depression-like phenotypes (such as body weight loss as well as depression- and anxiety-like behaviors) and improves synaptic survival and growth in the stratum of the CRS rats. Moreover, XYS reduces A2AR activity and suppresses hyper-activation of striatal microglia. The tissue and cellular effects of XYS were similar to those of the known A2AR antagonists. In conclusion, XYS alleviates depression in the CRS rats via inhibiting A2AR in the striatum.
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影响因子：
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DOI：
10.1073/pnas.1423088112
发表时间：
2015-06-23
影响因子：
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作者：
Kaster, Manuella P.;Machado, Nuno J.;Cunha, Rodrigo A.
通讯作者：
Cunha, Rodrigo A.