The Outcomes of Maternal Immune Activation Induced with the Viral Mimetic Poly I:C on Microglia in Exposed Rodent Offspring

Maternal immune activation (MIA) can result from a variety of maternal inflammatory factors, including metabolic disorders, nutritional deficits, infections, and psychosocial stress. MIA has been consistently recognized as a major risk factor for neurodevelopmental disorders, and this association seems to be especially important for viral infections, as viral exposure during pregnancy was associated with a higher risk of developing neurodevelopmental disorders, such as schizophrenia. In MIA, the gestational parent's inflammatory response to an immune stimulus alters or interrupts fetal development, triggering neurodevelopmental consequences. As MIA can occur in any pregnancy it is important to understand the many factors at play that contribute to altered brain development in the offspring, especially considering recent global events such as the COVID-19 pandemic. The underlying mechanisms by which MIA results in deleterious outcomes are not yet clear, but due to the inflammatory response it initiates, it is becoming apparent that microglia are critically involved. Through investigation of MIA animal models, the role of microglia in this field is becoming more evident. Compelling evidence from animal models indicates that MIA can disrupt synaptic pruning, neuronal progenitor cell proliferation /differentiation, oligodendrogenesis and more. Microglia appear as an active player, assisting these neural-related functions during healthy development, but also mediating MIA-induced disturbances in these critical processes when neurodevelopment is challenged. The present review illustrates this complex web by reviewing recent literature, focusing on the outcomes of MIA resulting from viral mimetic poly I:C in rodents, to provide a clear description of how MIA impacts microglial functions and what this means for the offspring's neurodevelopment. Moreover, we discuss the possible implications of the COVID-19 pandemic on the neurodevelopment of the current and next generations in the frame of MIA models and propose some putative pharmacological and non-pharmacological approaches to prevent or attenuate MIA consequences.

Automated summary

Maternal immune activation (MIA) caused by various factors such as metabolic disorders, infections, and stress, is recognized as a major risk factor for neurodevelopmental disorders, especially with viral infections. MIA alters fetal development and triggers neurodevelopmental consequences, with microglia playing a crucial role. Animal models suggest that MIA disrupts important processes like synaptic pruning and cell proliferation/differentiation, and the COVID-19 pandemic may have implications for neurodevelopment. This review focuses on the impact of viral mimetic poly I:C-induced MIA on microglial functions and proposes approaches to prevent or mitigate MIA consequences.