Basic & Clinical Medicine ›› 2021, Vol. 41 ›› Issue (6): 779-785.

• Original Articles •     Next Articles

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

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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