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CPEB1 在小鼠前扣带回皮层对内脏痛的影响。

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

机构信息

Department of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China.

Department of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China; The 154th Central Hospital of PLA, Xinyang 464000, China.

出版信息

Brain Res. 2019 Jun 1;1712:55-62. doi: 10.1016/j.brainres.2019.02.001. Epub 2019 Feb 4.

Abstract

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.

摘要

肠易激综合征患者患有慢性内脏疼痛,在其中一些患者中,这种疼痛伴有焦虑共病。细胞质多聚腺苷酸化元件结合蛋白 1(CPEB1)介导 mRNA 的细胞质多聚腺苷酸化,并促进其翻译。我们之前的研究表明,在炎症性疼痛的小鼠模型中,杏仁核中的 CPEB1 敲低具有抗焦虑作用,但没有镇痛作用。然而,CPEB1 在内脏疼痛调节中的前扣带皮层(ACC)中的作用尚不清楚。在这项研究中,通过向小鼠结肠注射酵母聚糖来建立内脏疼痛小鼠模型。酵母聚糖注射显著诱导小鼠内脏疼痛和焦虑样行为,并增加 ACC 中的 GluA1、磷酸化 GluA1 的 S845 和 S831 以及 CPEB1 的水平。通过 AAV-CPEB1-shRNA 在 ACC 中敲低 CPEB1 可降低酵母聚糖诱导的小鼠疼痛和焦虑样行为。这一观察结果与 AMPA 受体、突触小体蛋白和 PSD95 水平降低密切相关。这些数据表明,ACC 中的 CPEB1 是内脏疼痛和焦虑共病的潜在治疗靶点。

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