LATE PRENATAL INFECTION AND NEURODEVELOPMENTAL DISORDERS: CHARACTERIZATION OF AN IMMUNE-MEDIATED MOUSE MODEL

Compelling evidence suggests that the aetiology of multifactorial and multisymptomatic psychiatric diseases include exposures to adverse events during prenatal and early postnatal life, which may disrupt the correct maturation of neural system and lead to long-lasting changes in brain function. Prenatal insults, and in particular prenatal infection, could thus act as a “primer” for the neuropsychiatric route, even if the specificity of the illness that develops is strongly influenced by the genetic and environmental context in which the process occurs (Meyer, 2013b). A similar concept of “early-life programming of adult disease” has been put forward by the seminal work of David Barker conducted in the context of cardiovascular disease (Dover, 2009), suggesting that specific environmental factors acting during sensitive prenatal or early postnatal developmental periods can induce persistent changes in physiological, emotional and behavioural functions throughout life (Bale et al, 2010). Against this background, the aim of my PhD thesis was to investigate and further characterize an established murine model of prenatal infection that is based on maternal administration of the viral mimic polyriboinosinic-polyribocytidilic acid [Poly(I:C)], focusing on different aspects of the relationship between altered neurodevelopment and psychiatric disease. First, I will give an overview of the state of the art regarding the association between prenatal infection and different neurodevelopmental illnesses as identified by human epidemiological studies, and then I will present our preclinical results obtained in an experimental model system of prenatal immune activation.