Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses
Prenatal infections have been linked to the development of schizophrenia (SCZ) and other neurodevelopmental disorders in the offspring, and work in animal models indicates that this is to occur through the maternal inflammatory response triggered by infection. Several studies in animal models demonstrated that acute inflammatory episodes are sufficient to trigger brain alterations in the adult offspring, especially in the mesolimbic dopamine (DA) system, involved in the pathophysiology of SCZ and other disorders involving psychosis. In the current review, we synthesize the literature on the clinical studies implicating prenatal infectious events in the development of SCZ. Then, we summarize evidence from animal models of maternal immune activation (MIA) and the behavioral and molecular alterations relevant for the function of the DAergic system. Furthermore, we discuss the evidence supporting the involvement of maternal cytokines, such as interleukin 6 (IL-6) and leptin (a hormone with effects on inflammation) in mediating the effects of MIA on the fetal brain, leading to the long-lasting effects on the offspring. In particular, IL-6 has been involved in mediating the effects of MIA animal models in the offspring through actions on the placenta, induction of IL-17a, or triggering the decrease in non-heme iron (hypoferremia). Maternal infection is very likely interacting with additional genetic and environmental risk factors in the development of SCZ; systematically investigating how these interactions produce specific phenotypes is the next step in understanding the etiology of complex psychiatric disorders.
|Keywords||animal models, cytokines, dopamine, IL-6, iron, leptin, maternal infection, schizophrenia|
|Journal||Frontiers in Psychiatry|
Aguilar-Valles, A, Rodrigue, B. (Brandon), & Matta-Camacho, E. (Edna). (2020). Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses. Frontiers in Psychiatry (Vol. 11). doi:10.3389/fpsyt.2020.00852