PARP14在3种抑郁症模型小鼠海马区的表达升高及其与神经炎性反应的关系

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (5): 641-647.

PARP14在3种抑郁症模型小鼠海马区的表达升高及其与神经炎性反应的关系

李辰, 修建波, 许琪^*

中国医学科学院基础医学研究所北京协和医学院基础学院生物化学与分子生物学系医学分子生物学国家重点实验室,北京 100005

收稿日期:2021-01-22 修回日期:2021-03-20 出版日期:2021-05-05 发布日期:2021-05-06
通讯作者: ^*xuqi@pumc.edu.cn
基金资助:
国家自然科学基金(81625008, 81930104, 31970952);国家重点研发计划(2016YFC1306700, 2020YFA0804502);北京市科技计划(Z181100001518001);中国医学科学院创新工程项目(2016-I2M-1-004);广东省重点领域研发计划(2018B030334001)

PARP14 is increased in the hippocampus of three mouse depression models and its relationship with neuroinflammation

LI Chen, XIU Jian-bo, XU Qi^*

State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Science CAMS, School of Basic Medicine PUMC, Beijing 100005, China

Received:2021-01-22 Revised:2021-03-20 Online:2021-05-05 Published:2021-05-06
Contact: ^*xuqi@pumc.edu.cn

摘要/Abstract

摘要： 目的探究ADP核糖聚合酶14(PARP14)与抑郁症是否相关及其是否影响小胶质细胞的炎性反应。方法构建抑郁症小鼠模型,通过实时定量PCR和Western blot对比了慢性束缚(CRS)模型、慢性不可预知压力(CUMS)模型和脂多糖(LPS)模型,3种抑郁症模型小鼠抑郁症相关脑区中相比于对照组PARP14的蛋白及mRNA表达水平变化。而后在永生化小胶质细胞系BV2中检测其敲低及过表达Parp14后对炎性反应的影响。结果在3种抑郁症模型小鼠海马区均观察到了PARP 4表达水平相较于对照组的升高(P＜0.05),且在CRS模型组中观察到PARP14表达水平与组织中炎性反应因子的表达水平相关(P＜0.05)。LPS刺激小鼠永生化小胶质细胞系BV2后PARP14表达水平也随之升高(P＜0.05);同时过表达PARP14后的BV2细胞响应LPS刺激表达更多促炎性细胞因子(P＜0.01),而敲低Parp14或使用PARP14抑制剂处理后表现与其相反(P＜0.05)。结论抑郁模型小鼠海马区PARP14表达水平升高,这可能加剧小胶质细胞响应LPS的炎性反应,从而促使神经炎性反应水平升高。

关键词: 重度抑郁症, ADP核糖聚合酶14(PARP14), 神经炎性反应, 小胶质细胞

Abstract: Objective To explore whether ADP ribose polymerase 14(PARP14) is related to depression and does it affect the inflammatory response of microglia. Methods Three kinds of mouse depression model were established to find potential relationship between the expression level of PARP14 and the change in depression-related brain areas including chronic restraint(CRS)model, chronic unpredictable mild stress(CUMS)model, lipopolysaccharide (LPS) model. Then the effect of Parp14 over-expression and knockdown on inflammatory response was examined in immortalized microglia cell line BV2. Results The expression of PARP14 increased in the hippocampal tissues of all three kinds of depression models, and the expression of PARP14 in the CRS model group was correlated with the expression level of inflammatory response factors in the tissues. The expression level of PARP14 also increased after stimulation of mouse immortalized microglia cell line BV2 by LPS .At the same time, BV2 cells with over-expression of PARP14 expressed more pro-inflammatory cytokines as a response to LPS stimulation, while those with knockdown Parp14 or treatment with PARP14 inhibitor showed the opposite results. Conclusions This study shows that the expression level of PARP14 in the hippocampus of depression model mice increased, which may enhance the level of neuroinflammation and aggravate depression-like phenotype by exacerbating the :PS induced inflammatory response of microglia cells .

Key words: major depressive disorder, poly ADP-ribose polymerase 14(PARP14), neuroinflammation, microglia

中图分类号:

R338.2

李辰, 修建波, 许琪. PARP14在3种抑郁症模型小鼠海马区的表达升高及其与神经炎性反应的关系[J]. 基础医学与临床, 2021, 41(5): 641-647.

LI Chen, XIU Jian-bo, XU Qi. PARP14 is increased in the hippocampus of three mouse depression models and its relationship with neuroinflammation[J]. Basic & Clinical Medicine, 2021, 41(5): 641-647.

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