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Radiation-induced neurotoxicity: investigating human neuronal damage in MEA-integrated microfluidic platforms
Andie E Padilla1, Marion Jones1, Binata Joddar1
1Inspired Materials & Stem-Cell Based Tissue Engineering Laboratory, Chemical, Biological and Environmental Engineering, Oregon State University 313 Gleeson Hall, 2115 SW Campus Way Corvallis OR 97331 USA binata.joddar@oregonstate.edu.
RSC Advances
|March 23, 2026
Summary
Human neuronal networks in a 3D tissue-on-a-chip model showed reduced survival and function after gamma radiation. This research aids in understanding radiation risks for deep-space missions and astronaut health.
Area of Science:
- Neuroscience
- Radiation Biology
- Biomedical Engineering
Background:
- Human glutamatergic neuronal networks are crucial for brain function.
- Understanding the effects of ionizing radiation on neuronal networks is vital for space exploration.
- Traditional 2D cell cultures do not fully replicate the complex 3D microenvironment of human brain tissue.
Purpose of the Study:
- To assess the functional response of human neuronal networks to gamma radiation using a novel microelectrode array (MEA)-integrated 3D tissue-on-a-chip platform.
- To investigate radiation-induced neurodegeneration and its underlying mechanisms.
- To evaluate the utility of this platform for modeling extraterrestrial health risks.
Main Methods:
- Development and utilization of a novel MEA-integrated 3D tissue-on-a-chip platform for culturing human glutamatergic neurons.
- Exposure of neuronal networks to 2.5 Gy and 5 Gy gamma radiation.
- Real-time electrophysiology (EPHYS) monitoring, live/dead cell viability staining, biochemical assessments (creatine kinase), and DNA methylation analysis.
Main Results:
- Significant reduction in neuronal survival and delayed cell death observed in both 3D and 2D cultures post-irradiation.
- Progressive deterioration of neuronal network performance, including reduced firing frequency and action potential amplitude, over one week post-irradiation.
- Downregulation of creatine kinase (CK) and radiation-associated alterations in DNA methylation, indicating impaired metabolism and epigenetic changes.
Conclusions:
- Human neuronal systems are susceptible to ionizing radiation, exhibiting functional decline and molecular alterations.
- The MEA-integrated 3D tissue-on-a-chip platform accurately models radiation effects on human brain tissue and is valuable for assessing extraterrestrial health risks.
- Findings provide mechanistic insights into radiation-induced neurodegeneration, supporting the development of countermeasures for astronaut health in deep-space missions.
