A 3D in vitro cortical tissue model based on dense collagen to study the effects of gamma radiation on neuronal function

Abstract

Studies on gamma radiation-induced injury have long been focused on hematopoietic, gastrointestinal, and cardiovascular systems, yet little is known about the effects of gamma radiation on the function of human cortical tissue. The challenge in studying radiation-induced cortical injury is, in part, due to a lack of human tissue models and physiologically relevant readouts. Here, we have developed a physiologically relevant 3D collagen-based cortical tissue model (CTM) for studying the functional response of human iPSC derived neurons and astrocytes to a sub-lethal radiation exposure (5 Gy). We quantified cytotoxicity, DNA damage, morphology, and extracellular electrophysiology. We reported that 5 Gy exposure significantly increased cytotoxicity, DNA damage, and astrocyte reactivity while significantly decreased neurite length and neuronal network activity. Additionally, we found that clinically deployed radioprotectant amifostine ameliorated the DNA damage, cytotoxicity, and astrocyte reactivity. The CTM provides a critical experimental platform to understand cell-level mechanisms by which GR affects human cortical tissue and to screen prospective radioprotectant compounds.