Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism

Abstract

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 ten 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.

Maternal immune activation alters brain microRNA expression in mouse offspring

“…To investigate repetitive/stereotyped behaviors,19 we observed jumping and self‐grooming behaviors of tested mice in a clean, empty box for 10 min. The box was made of white plastic (40 × 40 × 40 cm).…”

Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment

“…Maternal effects on fetal development have been explored in other mouse models related to autism, but these studies have focused on environmental stressors that impact the prenatal environment (Bronson and Bale, 2014;Malkova et al, 2012). Recent studies related to mood and anxiety have indicated that genetic factors may also influence neurodevelopment by altering maternal physiology during pregnancy (Toth, 2014).…”

The Role of the Immune System in Autism Spectrum Disorder

“…The authors followed-up by challenging pregnant dams with either a single injected dose of influenza on embryonic day E9.5 or poly(I:C) on day E12.5; both groups had offspring with altered cerebellar development, akin to that seen in autism (Shi et al, 2009). A more expansive study injected pregnant mice three times with poly(I:C), each with one-fourth the dose of Shi, et al, starting on E10.5 and spaced with 2 days between injections (Malkova et al, 2012). The authors looked at ultrasonic vocalization (USV) responses among male offspring and found lower rates and total length of vocalizations.…”