GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity.
GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity.
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DOI：
10.3389/fnins.2021.703044
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发表时间：
2021
影响因子：
4.3
通讯作者：
Tian Z
中科院分区：
文献类型：
--
作者：
Wang Y;Han J;Zhu J;Zhang M;Ju M;Du Y;Tian Z
应激引起的下丘脑-垂体-肾上腺（HPA）轴功能亢进，必然会破坏神经内分泌系统的稳态，损害生理功能。已有研究表明，电针对围手术期HPA轴亢进具有调节作用。下丘脑促肾上腺皮质激素释放激素（CRH）作为HPA轴的启动因子，是电针影响下丘脑功能的关键分子。然而，EA减少CRH合成和分泌的机制仍不清楚。活化的N-甲基-D-天冬氨酸受体（NMDAR）与应激诱导的下丘脑CRH过度分泌有关。为探讨电针对CRH过度表达的调控作用是否与NMDA受体有关，本实验建立了大鼠部分肝切除术（HT）模型。观察电针对HT小鼠下丘脑NMDAR表达的影响。然后，我们研究了NMDAR介导的细胞外调节蛋白激酶（ERK）/环磷酸腺苷反应元件结合蛋白（CREB）信号通路是否参与了电针调节HPA轴亢进。结果发现，手术可引起下丘脑CRH表达增强，HPA轴功能亢进。有趣的是，EA有效地抑制了HT小鼠CRH的表达，并降低了GluN 2A（NMDAR亚基），ERK和CREB的活化。GluN 2A、ERK和CREB拮抗剂对CRH表达和HPA轴功能的正常化作用与EA相似。提示手术可增强下丘脑GluN 2A/ERK/CREB信号通路的激活，从而促进CRH的合成和分泌。电针可抑制手术小鼠的GluN 2A、ERK和CREB的磷酸化，提示GluN 2A/ERK/CREB信号通路参与了电针缓解HPA轴亢进的作用。手术诱导HPA轴亢进，而电针干预抑制下丘脑GluN 2A/ERK/CREB信号通路的激活，从而减少CRH的合成和分泌，减轻手术后HPA轴的亢进。
The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis caused by stress will inevitably disrupt the homeostasis of the neuroendocrine system and damage physiological functions. It has been demonstrated that electroacupuncture (EA) can modulate HPA axis hyperactivity during the perioperative period. As the initiating factor of the HPA axis, hypothalamic corticotrophin-releasing hormone (CRH) is the critical molecule affected by EA. However, the mechanism by which EA reduces CRH synthesis and secretion remains unclear. Activated N-methyl-D-aspartate receptor (NMDAR) has been linked to over-secretion of hypothalamic CRH induced by stress. To determine whether NMDAR is involved in EA regulating the over-expression of CRH, a surgical model of partial hepatectomy (HT) was established in our experiment. The effect of EA on hypothalamic NMDAR expression in HT mice was examined. Then, we investigated whether the extracellular regulated protein kinases (ERK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway mediated by NMDAR was involved in EA regulating HPA axis hyperactivity. It was found that surgery enhanced the expression of hypothalamic CRH and caused HPA axis hyperactivity. Intriguingly, EA effectively suppressed the expression of CRH and decreased the activation of GluN2A (NMDAR subunit), ERK, and CREB in HT mice. GluN2A, ERK, and CREB antagonists had similar effects on normalizing the expression of CRH and HPA axis function compared with EA. Our findings suggested that surgery enhanced the activation of the hypothalamic GluN2A/ERK/CREB signaling pathway, thus promoting the synthesis and secretion of CRH. EA suppressed the phosphorylation of GluN2A, ERK, and CREB in mice that had undergone surgery, indicating that the GluN2A/ERK/CREB signaling pathway was involved in EA alleviating HPA axis hyperactivity. Surgery induced HPA axis hyperactivity, while EA intervention inhibited the activation of hypothalamic GluN2A/ERK/CREB signaling pathway, thereby reducing the synthesis and secretion of CRH, alleviating the hyperactivity of the HPA axis after surgery.
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影响因子：
16.2
作者：
Liu S;Wang ZF;Su YS;Ray RS;Jing XH;Wang YQ;Ma Q
通讯作者：
Ma Q
影响因子：
3.7
作者：
Collison KS;Inglis A;Shibin S;Saleh S;Andres B;Ubungen R;Thiam J;Mata P;Al-Mohanna FA
通讯作者：
Al-Mohanna FA
影响因子：
4.5
作者：
Cherian, Kirsten;Schatzberg, Alan F.;Keller, Jennifer
通讯作者：
Keller, Jennifer
DOI：
10.3109/10253890.2013.806907
发表时间：
2014-01-01
影响因子：
2.3
作者：
Cope, Jessica L.;Regev, Limor;Baram, Tallie Z.
通讯作者：
Baram, Tallie Z.
DOI：
10.13702/j.1000-0607.170617
发表时间：
2018-12-25
期刊：
Zhen ci yan jiu = Acupuncture research
影响因子：
--
作者：
Geng, Yan-Xia;Chen, Dong;Diao, Ren-Zheng
通讯作者：
Diao, Ren-Zheng