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

By N. Malkova, Collin Z. Yu, E. Hsiao, Marlyn J. Moore, P. Patterson. Brain, behavior, and immunity, 2012

650 citations recorded by the source corpus.

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.

Subfields: Cognitive Neuroscience, Pharmacy, Social Psychology

View Paper: https://www.semanticscholar.org/paper/bbe866d5af28a30b901489c2d6bcf517ce78c241

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cognitive Neuroscience

1. P. Patterson
2. J. Cryan

In Pharmacy

1. J. Cryan
2. Ted G. Dinan
3. G. Clarke
4. S. Mazmanian
5. P. Kennedy
6. C. Stanton
7. J. Foster
8. T. Sampson

In Social Psychology

1. J. Cryan
2. Ted G. Dinan
3. S. Mazmanian
4. G. Clarke
5. P. Kennedy
6. E. Hsiao
7. P. Patterson
8. T. Sampson

Citations in the corpus

• Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation (2020, background): “Maternal infection or immune activation during pregnancy is another area of interest and may be a potential risk factor according to recent investigations (62-65).”
• Kynurenine pathway metabolism and the microbiota‐gut‐brain axis (2017, background): “The maternal immune activation model produces offspring exhibiting deficits in social behaviour, GI disturbances, increased intestinal permeability and alterations in the composition of the gut microbiota (Malkova et al., 2012).”
• The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring (2016, background): “As previously reported (7, 8), we found that prenatal exposure to MIA also caused social interaction deficits in adult offspring (Fig.”
• The microbiota modulates gut physiology and behavioral abnormalities associated with autism (2013, positive): “We replicated previous findings that adult MIA offspring display several core behavioral features of ASD (Malkova et al., 2012).”