Modeling the effects of radiation on neurogenesis using an in vitro neurogenic niche approach

Abstract

Radiation-induced neurocognitive dysfunction after brain radiotherapy is a growing concern among the increasing numbers of long-term cancer survivors, particularly in children. This dysfunction significantly impacts memory, learning, and overall quality of life. Neural stem and progenitor cells (NSPCs) play a vital role in maintaining neurogenesis and plasticity, processes essential for memory formation and cognitive resilience. Currently, no effective treatments exist, highlighting the urgent need for strategies to mitigate these effects. One potential contributing factor to this dysfunction is the depletion or dysregulation of NSPCs following radiation. Here, we developed an in vitro microfluidic neurogenic niche setup to investigate how non-irradiated NSPCs respond to the inflammatory secretome produced by irradiated human fetal astrocytes (HFA) and human brain microvascular endothelial cells (HBMEC). NSPCs viability was dose-dependently affected when exposed to conditioned media from irradiated cells. Notably, NSPCs exposed to conditioned media from cells irradiated at 2 Gy and 8 Gy exhibited increased expression of SOX9 and S100B, respectively, suggesting a shift toward a gliogenic fate. Our findings suggest that this microfluidic model is valuable for exploring radiation-induced neurocognitive dysfunction and identifying potential therapeutic targets.