The Impact of Maternal Immune Activation on Social Cognition in a Mouse Model of Neurodevelopmental Disorders



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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.



Autism, Maternal, Pregnancy, Immunity, Poly I:C