TLR3激活协同干扰素α抑制小鼠海马神经元DISC1表达

doi:10.16352/j.issn.1001-6325.2022.12.1855

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (12): 1855-1860.doi: 10.16352/j.issn.1001-6325.2022.12.1855

TLR3激活协同干扰素α抑制小鼠海马神经元DISC1表达

姚景宏¹, 李加欢¹, 刘子建^2*

1.华中科技大学同济医学院附属协和医院感染科, 湖北武汉 430022;
2.华中科技大学同济医学院基础医学院解剖学系,湖北武汉 430030

收稿日期:2021-11-08 修回日期:2022-04-19 出版日期:2022-12-05 发布日期:2022-11-23
通讯作者: ^* liuzj@mail.hust.edu.cn
基金资助:
中国肝炎防治基金会天晴肝病研究基金(TQGB20200137)

Toll-like receptor 3 activation combined with INFα inhibits the expression of DISC1 in hippocampal neurons of mice

YAO Jing-hong¹, LI Jia-huan¹, LIU Zi-jian^2*

1. Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022;
2. Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Received:2021-11-08 Revised:2022-04-19 Online:2022-12-05 Published:2022-11-23
Contact: ^* liuzj@mail.hust.edu.cn

摘要/Abstract

摘要： 目的研究TLR3激活对小鼠海马神经元的精神分裂症断裂基因1(DISC1)表达的影响。方法分离培养C57BL/6J小鼠E18海马神经元,给予1 μg/mL polyI:C或/和100 IU/mL mIFNα处理细胞24 h后,用RT-qPCR、免疫细胞化学和Western blot方法检测DISC1 mRNA和蛋白的表达,并检测p38丝裂原活化蛋白激酶(p38 MAPK)、信号传导和转录激活因子1(STAT1)及糖原合成激酶3β(GSK-3β)的磷酸化。结果相比对照组,polyI:C组和IFNα组DISC1 mRNA及蛋白水平无明显变化,而共刺激(IFNα+polyI:C)组DISC1表达显著下降(P＜0.05)。此外,polyI:C和共刺激组p38 MAPK磷酸化水平增加(P＜0.05),且IFNα和共刺激组STAT1磷酸化水平亦显著升高(P＜0.05),而GSK-3β磷酸化水平无变化。结论外源性IFNα协同TLR3激活可部分通过p38 MAPK和JAK/STAT1信号通路抑制DISC1的表达。

关键词: 精神分裂症断裂基因1, Toll样受体3, 干扰素α, 信号传导和转录激活因子1, p38丝裂原活化蛋白激酶

Abstract: Objective To explore the effect of Toll-like receptor 3 (TLR3) activation on the expression of neuronal disrupted-in-schizophrenia 1 (DISC1). Methods C57BL/6J mouse hippocampal neurons were incubated with polyI:C(1 μg/mL) or/and mIFNα(100 IU/mL) for 24 hrs. DISC1 mRNA and protein were detected by quantitive RT-PCR, immuno-cytochemistry staining and Western blot. The expression of STAT1, phospho-STAT1, p38 MAPK, phospho-p38 MAPK, GSK-3β, and phospho-GSK-3β was also detected by Western blot. Results Comparing with control group, the mRNA and protein expression of DISC1 in polyI:C group and IFNα group didn't show any changes, but significantly decreased with the co-stimulation by polyI:C and IFNα (P＜0.05). In addition, the phosphorylation of STAT1 was significantly increased in both IFNα group and co-stimulation group(P＜0.05) and the phosphorylation of p38 MAPK was elevated in polyI:C group and co-stimulation group (P＜0.05).The expression of GSK-3β and phospho-GSK-3β had no changes. Conclusions The combined stimulations of IFNα and TLR3 activation may inhibit the expression of DISC1 potentially through JAK/STAT1 and p38 MAPK signaling pathways.

Key words: disrupted-in-schizophrenia 1, Toll-like receptor 3, interferon α, STAT1, p38 MAPK

中图分类号:

R373.2

姚景宏, 李加欢, 刘子建. TLR3激活协同干扰素α抑制小鼠海马神经元DISC1表达[J]. 基础医学与临床, 2022, 42(12): 1855-1860.

YAO Jing-hong, LI Jia-huan, LIU Zi-jian. Toll-like receptor 3 activation combined with INFα inhibits the expression of DISC1 in hippocampal neurons of mice[J]. Basic & Clinical Medicine, 2022, 42(12): 1855-1860.

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TLR3激活协同干扰素α抑制小鼠海马神经元DISC1表达

Toll-like receptor 3 activation combined with INFα inhibits the expression of DISC1 in hippocampal neurons of mice

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