Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism
The core symptoms of autism are deficits in social interaction and language, and the presence of repetitive/stereotyped behaviors. We demonstrate that behaviors related to these symptoms are present in a mouse model of an environmental risk factor for autism, maternal infection. We stimulate the maternal immune system by injecting the viral mimic poly(I:C) during pregnancy, and analyze the social and communicative behaviors of the offspring. In one test, young pups respond to a brief separation from the mother with ultrasonic vocalizations (USVs). We find that, compared to pups born to saline-injected mothers, pups born to maternal immune activation (MIA) mothers produce a lower rate of USVs in the isolation test starting at day 8. The quality of the vocalizations is also different; analysis of sound spectrograms of 10 day-old pups shows that male pups from MIA mothers emit significantly fewer harmonic and more complex and short syllables. These communication differences are also apparent in adult offspring. Compared to controls, adult MIA males emit significantly fewer USVs in response to social encounters with females or males, and display reduced scent marking in response to female urine. Regarding a second autism symptom, MIA males display decreased sociability. In a third test of characteristic autism behaviors, MIA offspring exhibit increased repetitive/stereotyped behavior in both marble burying and self-grooming tests. In sum, these results indicate that MIA yields male offspring with deficient social and communicative behavior, as well as high levels of repetitive behaviors, all of which are hallmarks of autism.
© 2012 Elsevier Inc. Received 14 September 2011. Revised 8 December 2011. Accepted 17 January 2012. Available online 29 January 2012. The authors acknowledge the kind assistance of J. Ko and B. Deverman with reviewing the manuscript, L. Sandoval and R. Sauza for maintaining the animals, and J. Grimsley for providing advice on syllable analysis. This research was supported by the National Institute of Mental Health EUREKA award to PHP and NVM, and an Autism Speaks Dennis Weatherstone Pre-Doctoral Fellowship to EYH.
Accepted Version - nihms-354340.pdf
Supplemental Material - mmc1.doc