Effects of early-life infection and immune signaling on neural development

About This Grant

Project Summary Building a healthy adult brain requires the precise coordination of multiple developmental processes, including neural stem cell proliferation and differentiation, neuropil extension, synaptogenesis, and synaptic pruning. These processes are sensitive to genetic, environmental, and physiological conditions, and disruptions can have lasting consequences on brain structure, function, and behavior. Early-life immune activation, such as that triggered by infection, has been associated with impaired growth, cognitive deficits, and increased risk of metabolic syndrome later in life. However, the mechanisms linking immune activity during development to long- term neural outcomes remain poorly understood. This project investigates how systemic infection and innate immune signaling influence brain development and adult physiology. Neural stem cells depend on nutrient- responsive growth signaling pathways to support their proliferation and the production of neurons and glia. Preliminary data show that activation of a conserved innate immune pathway—whether through bacterial exposure or genetic manipulation—leads to reduced body and brain size and delays the reactivation of neural stem cells from quiescence. The central hypothesis is that early-life infection activates immune signaling that disrupts neurodevelopmental programs, leading to persistent changes in brain structure and function. This research will define how immune activation alters neural stem cell behavior, impacts brain growth, and shapes adult behavioral outcomes. The findings will provide insight into how developmental immune stressors influence long-term brain health and may inform our understanding of neurodevelopmental disorders associated with early-life inflammation.