Maternal Viral Infection Alters the Social and Anxiety-Like Behaviour of the Offspring

Background: Early immune challenge during critical periods of development may influence the trajectory of CNS development. In particular, viral challenge in utero has been shown to result in molecular and behavioural changes in the offspring. In the present study, we examined the impact of prenatal immune activation using the viral mimic, polyriboinosinic-polyriobytidilic acid (Poly I:C) on the development of autistic-like behaviours over the lifespan in mice. Objectives: The objective of these experiments was to examine both social behaviour and anxiety-like behaviours following exposure to poly I:C in utero. Methods: Pregnant dams (CD1 mice) were given an i.p. injection (5mg/kg) of Poly I:C or saline on embryonic day 10. Social behaviour of the pups was assessed on postnatal day 17 (P17) and 12 weeks of age using a three-chamber apparatus. In this 2-stage testing paradigm, variation in frequency of interaction ("sociability") to a stranger mouse was tested and followed by an assessment of frequency of interaction to a familiar vs. stranger mouse (social novelty). Locomotor and exploratory behaviour was assessed at P25 using activity chambers. Anxiety-like behaviour was also assessed at 6 weeks of age using the elevated plus maze (EPM). Results: Our social behaviour analysis revealed an early deficit in both sociability and social novelty at P17, whereas at 12 weeks of age Poly I:C mice showed normal sociability and social novelty. While no differences were apparent in exploratory or locomotor activity at P25, we did observe increased anxiety-like behaviour in Poly I:C mice at 6 weeks of age. These data show that maternal immune challenge leads to alterations in the developmental behavioural trajectory of offspring in both socialbility and anxiety. The observed preweaning deficits in social behaviour in Poly I:C mice are concurrent with the critical developmental period for the emergence of anxiety-like behaviour in mice. Conclusions: Together with the observed increase in anxiety-like behaviour during adolescence, these findings suggest a link between the development of social behaviour and the molecular substrate underlying the emergence of anxiety-like behaviour. We plan to investigate the molecular signature underlying this behavioural phenotype. This work may provide important insights regarding the inter-relationship between co-morbid anxiety and social deficits in autism and changes in this dynamic across development.