Maternal Immune Activation Induced by Prenatal Lipopolysaccharide Exposure Leads to Long-Lasting Autistic-like Social, Cognitive and Immune Alterations in Male Wistar Rats

Abstract

Several studies have supported the association between maternal immune activation (MIA) caused by exposure to pathogens or inflammation during critical periods of gestation and an increased susceptibility to the development of various psychiatric and neurological disorders, including autism and other neurodevelopmental disorders (NDDs), in the offspring. In the present work, we aimed to provide extensive characterization of the short- and long-term consequences of MIA in the offspring, both at the behavioral and immunological level. To this end, we exposed Wistar rat dams to Lipopolysaccharide and tested the infant, adolescent and adult offspring across several behavioral domains relevant to human psychopathological traits. Furthermore, we also measured plasmatic inflammatory markers both at adolescence and adulthood. Our results support the hypothesis of a deleterious impact of MIA on the neurobehavioral development of the offspring: we found deficits in the communicative, social and cognitive domains, together with stereotypic-like behaviors and an altered inflammatory profile at the systemic level. Although the precise mechanisms underlying the role of neuroinflammatory states in neurodevelopment need to be clarified, this study contributes to a better understanding of the impact of MIA on the risk of developing behavioral deficits and psychiatric illness in the offspring.

The PPARα Agonist Fenofibrate Reduces the Levels of Proinflammatory Cytokines in a Maternal Immune Activation Model of Schizophrenia

“…Several studies in animal models have concurred to unveil the relationship between MIA and altered fetal neurodevelopment, which might lead to long-term anatomical and behavioral impairments correlated with inflammation [6][7][8]. Thus, preclinical and clinical studies showed that MIA triggers a cytokine imbalance that increases the risk of neurodevelopmental disorders in the offspring [9][10][11][12]. Both rodent and non-human primate models took advantage of the polyriboinosinic-polyribocytidylic acid [poly (I:C)], a double-stranded synthetic RNA that elicits an innate immune response by simulating a viral infection.…”