14:10-14:30 Early origins of neurodevelopmental disorders

The intrauterine period of life represents a highly sensitive developmental time window, because of complex cellular and molecular interactions, ensuring healthy brain maturation. Besides maternal influences that promote healthy brain maturation, accumulating evidence also suggests that maternal mediators such as pro-inflammatory cytokines or obesity may adversely affect the developing brain favoring cognitive and behavioral impairments in childhood and beyond. Impairments of such cognitive and behavioral performances are summarized as a set of psychiatric and neurological disorders with neurodevelopmental etiology. Worldwide more over 3% of all children are suffering from such a disorder combining impaired cognitive function, communication, and behavior. Even though the heterogeneity in behavioral and cognitive phenotypes may suggest a heterogenous origin of these disorders, not only the inheritance of genetic repertoires, but also shared molecular and cellular pathways have been investigated. Over the last years, maternal molecular and cellular mediators have been proposed to cross the placenta, shape fetal microglia development and their activity. Microglia originate from myeloid progenitor cells in the yolk sac and invade the developing brain during embryonic life. It has been shown that microglia and immune-related proteins are essential for the elimination and refinement of synaptic connectivity. A cyclic microglia activity during these early days of brain development has been considered as a healthy process of sculpting the neuronal landscape. As supposed to that, once microglia were triggered by maternally-derived molecular and cellular mediators, it is assumed that their activity can be altered into a chronic process. To date, insights into how chronic and cyclic microglia activity is induced, and by that determine functional and structural brain alterations is extremely sparse. We will present how maternal mediators that were associated with functional and structural brain alterations early in human life as well as results from pre-clinical models that elucidated a variety of mechanisms, accounting for such observed alterations and behavioral phenotypes later in life.