Human neurospheres on microelectrode arrays: a model to investigate ionizing radiation effects on neuronal network communication

Ionizing radiation is known to induce numerous effects in cells including cell cycle delay, DNA damage, altered gene expression and cell death. Although there are serious impacts on the organisms, the effects on prenatal development are largely unknown. Data regarding potential biological effects on the prenatal development after in utero radiation exposure predominantly stem from atomic bomb survivors and from animal studies. These results indicate that the developing central nervous system is particularly sensitive to ionizing radiation and that exposure can lead to prenatal death, growth retardation, organ malformation or mental retardation [1]. Yet, there is hardly any information on the effects of ionizing radiation on neuronal network communication, the most vital function of neurons. To fill this gap we developed a protocol that enables electrical characterization of three-dimensional neurospheres (NS) derived from human embryonic stem cells using microelectrode arrays (MEA). This method allows assessing the electrical activity of neuronal tissue in a non-invasive way. Network functionality typically develops in three phases. First, electrical activity can be detected as random single spikes. In a second phase train-like spiking activity evolves, that further develops into burstlike activity. These bursts represent the mature signalling activity of the network [2]. The measurement of electrical activity of neurospheres on MEAs represents a new and promising tool to investigate the effects of ionizing radiation on the neuronal network communication during early brain development.