The Impact of Maternal Immune Activation on Social Cognition in a Mouse Model of Neurodevelopmental Disorders
Date
2015-07-01
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Abstract
Many neurodevelopmental disorders like Autism and Schizophrenia are
characterized by pervasive social behavior deficits, etiologically explained
through both genetic and environmental factors. Epidemiological reports have
linked maternal exposure to high- grade fever or viral infection during the second
and third trimesters of pregnancy with increased risk of having a child later
diagnosed with a neurodevelopmental disorder, including Autism and
Schizophrenia. It is thought that in-utero exposure to an elevated maternal
immune response, rather than a specific pathogen is likely mediating the increased
risk of these disorders. Murine models of maternal immune activation (MIA) use
Poly I:C (polyinosinic–polycytidylic acid), a viral mimic that is a toll like
receptor-3 agonist, to induce an elevated immune response in the mother resulting
in deficits in social approach behavior in the offspring. However, neural processes
contributing to these social behavior deficits are unknown and may be linked to
alterations in social cognitive development, suggesting that MIA might mediate
deficits in social recognition as well. To test this hypothesis, this study utilized the
Poly I:C MIA model in C57 Bl/ 6J mice to study the effects of maternal immune
activation on social recognition behavior in offspring.
Pregnant dams were intraperitoneally injected with a single dose of either
20mg/kg Poly I:C or saline on gestational day 12.5; offspring were weaned on
post-natal day (PND) 21 and a social recognition behavioral test was conducted at
3
PND 30, and again at PND 60. Typically developing control offspring from
saline-treated dams showed robust social recognition during the juvenile period
and this social memory was maintained in saline offspring when re-tested at PND
60. Conversely, offspring of Poly I:C-treated dams were found to show no
preference between novel and littermate mice at PND30, indicating deficits in
recognizing novel versus familiar social stimuli, and spent more time with the
familiar littermate mice at PND 60. These data suggest that maternal immune
activation mediates a delay in social cognitive and social recognition abilities and
support the notion that cognitive and recognition deficits might be impacting the
social behavior deficits observed in neurodevelopmental disorders like Autism
and Schizophrenia.
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Keywords
Autism, Maternal, Pregnancy, Immunity, Poly I:C