• Maternal Immune Activation in Mice: A Longitudinal Analysis in the C57 Strain

Background:  Potential environmental risk factors for autism spectrum disorders (ASD) include viral/bacterial infection and rodent models of maternal immune activations have been developed and widely used also in preclinical studies to test treatment effectiveness.

Objectives: The present study investigated short- and long-term neurobehavioural effects of administration of immune factors during gestation to mimic a maternal viral infection.

Methods:  Polyinosinic-polycytidylic acid (Poly I:C), a synthetic analog of double-stranded RNA to mimic a viral infection, was injected into pregnant  C57BL6/j dams on gestational day 12.5.  Neonatal behavioural responses (ultrasonic vocalizations and spontaneous motor patterns) were measured on postnatal days 4, 7 and 10; at adulthood sociability in the three-chamber test, exploration in an open field test and marble burying behaviour were assessed. The experimental design includes 10/12 litters in each treatment group and data were analysed considering the litter-effect.   

Results:   Neonatal vocalizations were altered in Poly I:C pups: a reduction in vocalization rate was evident on pnd 10, with males more affected than females. As for spontaneous motor responses, Poly I:C male pups show an hyperlocomotor profile, with higher levels of pivoting/locomotion throughout the ages considered. An altered locomotor profile was still evident in adult Poly I:C male at adulthood, with lack of the expected habituation and less anxious profiles evident in the last part of a one-hour open field test; in Poly I:C males also increased stereotyped rearing responses were evident. In the three-chamber sociability test, Poly I:C treated mice (both sexes) show an increased sniffing response of the cage not containing the social stimulus, whereas a reduced response to novelty was evident in Poly I:C males.    

Conclusions:  Prenatal immune activation induces neonatal behavioural alterations in both vocal and motor domains that are more evident in males. The behavioural effects at adulthood appear more robust in explorative/stereotyped motor domains, more limited in the social competences, as measured in the three-chamber test, suggesting a more cautious use of these mice as a full model of ASD.