Effects of CPEB1 in the anterior cingulate cortex on visceral pain in mice

Effects of CPEB1 in the anterior cingulate cortex on visceral pain in mice
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前扣带皮层 CPEB1 对小鼠内脏痛的影响

DOI:
10.1016/j.brainres.2019.02.001
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发表时间:
2019-06
期刊:
Brain Res
影响因子:
--
通讯作者:
Liu S. B.
Liu S. B.
中科院分区:
其他
文献类型:
--
作者:
Wang X. S;Yue J;Hu L. N;Tian Z;Yang L. K;Lu L;Zhao M. G;Liu S. B.

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肠易激综合征患者患有慢性内脏疼痛,其中一些患者伴有焦虑共病。胞质多聚腺苷酸化元件结合蛋白1(CPEB 1)介导mRNA的胞质多聚腺苷酸化并促进其翻译。我们先前的研究表明,在炎症性疼痛的小鼠模型中,杏仁核中的CPEB 1敲低产生抗焦虑作用,但不产生镇痛作用。然而,CPEB 1在前扣带皮层(ACC)内脏痛调制中的作用仍不清楚。本研究采用小鼠结肠内注射酵母多糖的方法,建立小鼠内脏痛模型。酵母多糖注射显著诱导小鼠内脏疼痛和焦虑样行为,并增加ACC中GluA 1、S845和S831磷酸化GluA 1和CPEB 1的水平。通过AAV-CPEB 1-shRNA敲低ACC中的CPEB 1可减少酵母多糖诱导的小鼠疼痛和焦虑样行为。这一观察结果与AMPA受体、突触素和PSD 95水平降低密切相关。这些数据表明,ACC中的CPEB 1是内脏疼痛和焦虑合并症的潜在治疗靶点。
Patients with irritable bowel syndrome suffer from chronic visceral pain, and in some of them, this is accompanied by anxiety comorbidity. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the cytoplasmic polyadenylation of mRNAs and facilitates their translation. Our previous studies have shown that CPEB1 knockdown in the amygdala exerts anxiolytic but not analgesic effects in a mouse model of inflammatory pain. However, the roles of CPEB1 in the anterior cingulate cortex (ACC) in visceral pain modulation remain unclear. In this study, a visceral pain mouse model was established by injecting zymosan into the colon of mice. Zymosan injection significantly induced visceral pain- and anxiety-like behaviors in mice and increased the levels of GluA1, phosphorylated GluA1 at S845 and S831, and CPEB1 in the ACC. CPEB1 knockdown in the ACC by AAV-CPEB1-shRNA reduced zymosan-induced pain- and anxiety-like behaviors in mice. This observation was closely correlated with reduced AMPA receptor, synaptophysin, and PSD95 levels. These data suggest that CPEB1 in the ACC is a potential therapeutic target for visceral pain and anxiety comorbidity.
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