Poly I:C-induced maternal immune activation causes schizophrenia- like memory and prepulse inhibition deficits in the offspring by upregulating IL-6

Poly I:C-induced maternal immune activation(MIA) during gestation increases the risk of schizophrenia-like behaviors in the offspring. However, the molecular mechanism of poly I:C MIA-induced schizophrenia-like behaviors in the offspring is not well clarified. Available evidence showed that patients with schizophrenia have higher IL-6 levels in the blood and cerebrospinal fluid, which is correlated with psychotic and cognitive impairments. Previous findings suggest a key role for IL-6 in poly I:C MIA-induced schizophrenia-like abnormal behaviors. In the present study, we found that prenatal poly I:C exposure at gestational day (GD) 9 increased the expression of IL-6 and IL-6Rα and led to impaired prepulse inhibition (PPI) and recognition memory in adolescent and adult offspring. We also found that the expression and phosphorylation of IKKα/β, NF-κB, JAK2, and STAT3, the upstream and downstream signal molecules of IL-6, were increased in adolescent and adult offspring of poly I:C-treated mothers at GD 9. The increases in the expression of IL-6, IL-6Rα, IKKα/β, NF-κB, JAK2, and STAT3 and the impairments in PPI and recognition memory were alleviated by IL-6 blockade. These results suggest that IL-6 may be a potential mediator between NF-κB and JAK/STAT cross-talk, thereby contributing to poly I:C MIA-induced impairments in PPI and recognition memory in offspring. Our findings show that blocking of IL-6 could ameliorate prenatal poly I:C exposure-induced schizophrenia-like impairments in adolescent and adult offspring. Our study provides additional insight that targeting IL-6 is a potential strategy for treating poly I:C MIA-induced schizophrenia-like behaviors and behavioral deficits in schizophrenia. • Prenatal poly I:C exposure increased IL-6 and IL-6Rα expression in adolescent and adult offspring. • Prenatal poly I:C exposure led to impaired PPI and memory in adolescent and adult offspring. • Prenatal poly I:C exposure increased the expression of IKKα/β, NF-κB, JAK2, and STAT3 in adolescent and adult offspring. • Blocking IL-6 reversed increases in the expression of IL-6, IL-6Rα, IKKα/β, NF-κB, JAK2, and STAT3 and impairments in PPI and memory in adolescent and adult offspring. • IL-6 may be a potential mediator between NF-κB and JAK/STAT cross-talk, thereby contributing to poly I:C MIA-induced impairments in PPI and recognition memory in adolescent and adult offspring.