The role of mast cells in shaping neonatal hippocampal development

Abstract

Imbalances in the relationship between neuronal and immune cells in the CNS during development cause inflammatory cascades which drive neurodevelopmental disorders, including autism and schizophrenia. Exploration of mast cells (MC), an innate immune cell prototypically involved with allergy and atopy, in the developing CNS revealed a dense population lining the choroid fissure of the lateral ventricles, however factors recruiting MCs to this region and their brain-specific activities are not known. Here, we sought novel insights into the origin and regulation of this large population of MCs adjacent to the hippocampus throughout development. We discovered that MCs in the lateral ventricles of the neonatal brain replicate vigorously during the first week of life and are locally maintained near the hippocampus for only a narrow window embryonically and postnatally. These mast cells promote microglial genesis and depress microglial maturation in the hippocampus. We have begun to explore how MC activation by environmental stressors, including neonatal allergy, impact the homeostatic balance between these immune and glial cells. Exploration of brain MCs during development will frame our understanding of how peripheral inflammation destabilizes this normally harmonious relationship between MCs and developing neuronal niches.