Maternal viral infection during pregnancy affects gene expression of offspring in pons and medulla oblongata after bacterial infection

Abstract

Viral and bacterial infections during pregnancy are risk factors for autism spectrum disorder (ASD) and schizophrenia in offspring. Polyinosinic-polycytidylic acid (poly I:C) and lipopolysaccharide (LPS) are often used as models for viral and bacterial infections, respectively. Maternal immune activation (MIA) using poly I:C or LPS is an animal model for studying ASD and schizophrenia. MIA induces abnormal behaviors in offspring, including anxiety- and depression-like behaviors and reduced social interactions. Neonates are immunologically immature and therefore susceptible to infections. Thus, a two-hit immune activation model was created in which a pseudo-viral infection occurs during pregnancy, followed by a pseudo-bacterial infection during the neonatal period. In this study, we induced a pseudo-bacterial infection (LPS administration) on postnatal day (P) 11 in pups born to rats infected with a pseudo-virus (poly I:C administration) on gestational day 10. Offspring administered LPS on P 11 due to viral infection during pregnancy had a significantly higher mortality rate, at 76.9 %, compared to 24.0 % in the control group. Furthermore, blood biochemistry test results revealed that viral infections during pregnancy are associated with decreased levels of calcium, phosphate and triacylglycerol, and increased levels of lactate dehydrogenase and total bilirubin. Although abnormalities in the pons and medulla oblongata are suspected in both ASD and schizophrenia, few studies have examined gene expression in these regions. Therefore, we analyzed gene expression in these regions using DNA microarrays. The results showed that the expression of a number of genes changed by more than twofold. These results suggest that the abnormal gene expression in the pons and medulla oblongata affected by MIA may increase vulnerability to LPS.