A 3D In Vitro Cortical Tissue Model Based on Dense Collagen to Study the Effects of Gamma Radiation on Neuronal...

Area of Science:

• Neuroscience
• Radiation Biology
• Biomedical Engineering

Background:

• Gamma radiation (GR) injury research traditionally focuses on systemic effects, neglecting human cortical tissue.
• Understanding GR's impact on the brain is limited by a lack of suitable human tissue models.

Purpose of the Study:

• To develop a 3D collagen-based cortical tissue model (CTM) for studying human iPSC-derived neurons and astrocytes.
• To investigate the functional response of human cortical tissue to sub-lethal gamma radiation exposure (5 Gy).
• To evaluate the efficacy of the radioprotectant amifostine.

Main Methods:

• Development of a 3D collagen-based cortical tissue model (CTM) using human induced pluripotent stem cell (iPSC)-derived neurons and astrocytes.
• Exposure of the CTM to 5 Gy of gamma radiation.
• Quantification of cytotoxicity, DNA damage, cell morphology, and extracellular electrophysiology.
• Assessment of amifostine's protective effects.

Main Results:

• 5 Gy gamma radiation significantly increased cytotoxicity, DNA damage, and astrocyte reactivity.
• Neurite length and neuronal network activity were significantly decreased post-irradiation.
• Amifostine treatment ameliorated radiation-induced DNA damage, cytotoxicity, and astrocyte reactivity.

Conclusions:

• The developed CTM is a physiologically relevant platform for studying gamma radiation effects on human cortical tissue.
• Gamma radiation impairs neuronal function and network activity in a human cortical model.
• Amifostine demonstrates radioprotective capabilities in this human cortical tissue model.