Increased NRSF/REST in anterior cingulate cortex contributes to diabetes-related neuropathic pain
Increased NRSF/REST in anterior cingulate cortex contributes to diabetes-related neuropathic pain
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前扣带皮层 NRSF/REST 增加导致糖尿病相关神经性疼痛
DOI：
10.1016/j.bbrc.2020.04.106
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发表时间：
2020
影响因子：
3.1
通讯作者：
Guo Jing-Chun
中科院分区：
文献类型：
--
作者：
Xu Xiao-Die;Wen Xiao-Hong;He Cheng-Feng;Yu Zhong-Yu;Wang Jian-Tao;Zhou Hou-Guang;Guo Jing-Chun
糖尿病神经性疼痛是糖尿病最常见的并发症之一。中枢调节的机制仍不清楚。在这里，我们研究了神经元限制性沉默因子（NRSF/REST）在糖尿病相关神经性疼痛中的作用。评估机械异常性疼痛和热痛觉过敏以评价疼痛行为。我们的结果发现，在 db/db 小鼠的前扣带皮层 (ACC) 中，NRSF/REST 水平显着增加。 NRSF/REST 的减少改善了疼痛感。同时，体外研究发现，高葡萄糖和高棕榈酸治疗会诱导 NRSF/REST 及其辅助因子（mSin3A、CoREST 和 HDAC1）升高，而 GluR2 和 NMDAR2B 下调。 NRSF/REST 的敲低可以减弱 LDH 的释放，并部分逆转 HDAC1 和 NMDAR2B 的表达变化。我们的结果表明，db/db 小鼠 ACC 区 NRSF/REST 的升高是糖尿病神经性疼痛的关键介质之一。
Diabetic neuropathic pain is one of the most common complications of diabetes. Mechanisms underlying the central modulation are still unclear. Here, we investigated the role of the neuron-restricted silencing factor (NRSF/REST) in diabetic-related neuropathic pain. Mechanical allodynia and thermal hyperalgesia were assessed to evaluate painful behaviors. Our results found that in the anterior cingulate cortex (ACC) of db/db mice, NRSF/REST levels increased significantly. Reduction of NRSF/REST improved the painful sensation. Meanwhile, in vitro study found that high glucose and high palmitic acid treatment induced elevation of NRSF/REST and its cofactors (mSin3A, CoREST and HDAC1), whereas downregulation of GluR2 and NMDAR2B. Knockdown of NRSF/REST could attenuate the LDH release and partially reversed the expression changes of HDAC1 and NMDAR2B. Our results suggested that the elevation of NRSF/REST in the ACC area of db/db mice is one of the key mediators of diabetic neuropathic pain.