Hypothalamic paraventricular nucleus neurons activated by estrogen GPER1 receptors promote anti-inflammation effects in the early stage of colitis
Hypothalamic paraventricular nucleus neurons activated by estrogen GPER1 receptors promote anti-inflammation effects in the early stage of colitis
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雌激素GPER1受体激活下丘脑室旁核神经元促进结肠炎早期抗炎作用
DOI：
10.1093/abbs/gmz122
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Daxiang Wen
中科院分区：
文献类型：
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作者：
Tao Jiang;Ruoxi Wang;Wen Yin;Yuxi Zhou;Dexu Kong;Saihong Xu;Po Gao;Weifeng Yu;Yingfu Jiao;Daxiang Wen
下丘脑-垂体-肾上腺（HPA）轴参与了肠-脑的相互作用，肠道的病理性炎症过程可诱导HPA轴参与的“战或逃”反应，从而抑制或促进肠道炎症反应。下丘脑室旁核（PVN）神经元负责控制HPA轴活动，但它们在调节肠道炎症中的确切作用尚不清楚。在这项研究中，我们使用葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎模型，基因编辑和RNA干扰来确定PVN神经元对肠道炎症的影响。我们发现，在DSS治疗后的早期阶段（第三天），结直肠区域有轻度炎症，PVN神经元活化增加，但邻近区域没有。同时，约80%的激活的PVN神经元也表达新的雌激素GPER 1受体。结肠炎在GPER 1敲除小鼠和局部PVN GPER 1敲除小鼠中明显恶化。这些结果表明，PVN GPER 1阳性神经元在DSS诱导的结肠炎的早期阶段可能具有保护功能，这可能是中枢神经系统试图抑制肠道炎症以实现自我保护的机制。
The hypothalamus–pituitary–adrenal (HPA) axis is known to mediate gut–brain interaction, and the pathological inflammatory process in the intestine can induce HPA axis involved ‘fight or flight’ response to suppress or facilitate intestinal inflammation. Hypothalamic paraventricular nucleus (PVN) neurons are responsible for controlling the HPA axis activity, but their exact role in modulating intestinal inflammation remains unclear. In this study, we used the dextran sulfate sodium (DSS)-induced mice colitis model, gene editing, and RNA interference to determine the effects of PVN neurons on intestinal inflammation. We found that at the early stage (third day) after DSS treatment, there was a mild inflammation in the colorectal area and an increased neuron activation in the PVN but not in the adjacent area. At the same time, ~80% of activated PVN neurons also expressed novel estrogen GPER1 receptor. The colitis noticeably worsened in GPER1-knockout mice and local PVN GPER1-knockdown mice. These results indicated that PVN GPER1 positive neurons potentially have a protective function during the early stages of DSS-induced colitis, and this may be a mechanism by which the central nervous system attempts to suppress intestinal inflammation to achieve self-protection.