Sex-dependent behavioral alterations in a poly(I:C)-induced maternal immune activation model without segment filamentous bacteria

Abstract

Abstract Maternal immune activation is one of the major environmental risk factors for offspring to develop psychiatric disorders. A synthetic viral mimetic immunogen, polyinosinic-polycytidylic acid (poly(I:C)), has often been used to induce maternal immune activation in animal models of psychiatric disorders. In the mouse poly(I:C) model, the existence of segment filamentous bacteria (SFB) in the maternal intestine has been reported to be important for the induction of ASD-related behavioral alterations as well as atypical cortical development called cortical patches. This study aimed to elucidate the effect of poly(I:C) in the absence of intestinal SFB, which was maintained by vancomycin drinking. The poly(I:C) was administered at various time points between embryonic Day 9 to 16. In this condition, cortical patches were not observed at postnatal Day 0 or 1. The conspicuous PPI deficit of male adult offspring was observed in a poly(I:C) time-dependent manner, whereas the effect on females appeared less clear. On the other hand, a notable deficit in social interaction was observed in female mice, whereas males were less affected. This study revealed sex-dependent behavioral alterations in the mouse poly(I:C) model in the SFB-negative condition.