Prenatal Exposure to the Viral Mimetic Poly I:C Alters Fetal Brain Cytokine Expression and Postnatal Behaviour

Abstract

An increased incidence of mental illness disorders is found in children and adolescents born to mothers who experienced an infection-based illness during pregnancy. Animal models to study the prenatal origin of such outcomes of pregnancy have largely used conventional rodents, which are immature (altricial) at birth compared with the human neonate. In this study, we used the precocial spiny mouse (Acomys cahirinus), whose offspring have completed organogenesis at birth, and administered a single subcutaneous injection of a 5 mg/kg dose of the viral mimetic poly I:C (polyriboinosinic-polyribocytidylic acid) at mid gestation (20 days; term is 39 days). Prenatal exposure to poly I:C caused a transient weight loss in the pregnant dam, produced a downregulation of the proinflammatory cytokine tumour necrosis factor-α in the fetal brain, and resulted in abnormalities in sensorimotor gating and reduced social interaction, memory and learning in juvenile offspring. No changes in exploratory activity or anxiety and fear behaviours were found between the treatment groups. This study provides evidence that, in a rodent model that more closely resembles human brain development, prenatal infection can lead to behavioural abnormalities in postnatal life.