基础医学与临床 ›› 2021, Vol. 41 ›› Issue (6): 779-785.

• 研究论文 •    下一篇

精神分裂症“二次打击”小鼠模型的建立与评价

尤鹏升, 韦晖, 许琪*   

  1. 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:2021-02-24 修回日期:2021-04-16 出版日期:2021-06-05 发布日期:2021-05-31
  • 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)

Establishment and evaluation of a two-hit model of mouse schizophrenia

YOU Peng-sheng, WEI Hui, XU Qi*   

  1. 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:2021-02-24 Revised:2021-04-16 Online:2021-06-05 Published:2021-05-31
  • Contact: *xuqi@pumc.edu.cn

摘要: 目的 探究精神分裂症的风险因素孕期感染和产后炎性反应对疾病表型是否具有累加效应。方法 给GD 9.5孕鼠腹腔注射聚肌胞苷酸建立母体免疫激活模型,其子代于青春期或成年早期再次注射poly Ⅰ:C,建立“二次打击”小鼠模型:1)通过ELISA和RT-qPCR检测模型小鼠外周血和大脑中的炎性因子表达; 2)通过前脉冲抑制和MK-801诱导的自发活动等行为学实验,检测小鼠的精神分裂症表型。结果 1) MIA小鼠成年后表现出明显的行为学改变,如感觉运动门控障碍、MK-801的高敏感性等,且雌性小鼠受累程度较雄性小鼠更重;2)“二次打击”之后,MIA小鼠的感觉运动门控障碍减轻,精神分裂症相关表型部分缓解。结论 青春期或成年早期的炎性反应与孕期感染间不存在协同的病理效应。

关键词: 精神分裂症, 母体免疫激活, 二次打击, poly Ⅰ:C

Abstract: Objective Prenatal infection and postpartum inflammatory experiences have been associated with increased risk of schizophrenia. To explore whether prenatal immune activation and prepubertal inflammation have cumulative impact on vulnerability to schizophrenia. Methods Polyinosinin-polycytidylic acid was injected into pregnant mice to establish maternal immune activation models on gestation day 9.5. Offspring were treated with poly I:C during puberty or adulthood as the second hit. 1)Using ELISA and quantitative real-time PCR to detect inflammatory response after administration of poly Ⅰ:C. 2)The effects of single or combined exposure to prenatal immune activation and prepubertal inflammation were examined by prepulse inhibition and locomotor reactions to dizocilpine(MK-801). Behavioral assessment took place when the animals reached adulthood. Results 1)Offspring from poly Ⅰ:C -treated mothers showed sensorimotor gating deficiency, as well as in the precipitation of behavioral hypersensitivity to the drugs dizocilpine, which were similar with schizophrenia. The phenotype of female was more pronounced than male. 2)However, double-hit model's sensorimotor gating deficient level was lower than that of prenatal immune activation model, and the phenotype of schizophrenia was relieved after second hit. Conclusions There is no synergistic pathological effect of prenatal immune activation plus pre-pubertal or adulthood inflammation.

Key words: schizophrenia, maternal immune activation, two-hit, poly Ⅰ:C

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