Molecular and morphological changes induced by ionising radiation on maturing neurons

With exception for radiotherapy, many examinations deliver relatively low doses of radiations. However, the effect during the fetal stage or the childhood is considerable because of this particularly radiosensitive period, in which cells such as neurons are still maturating. Their damage may lead to abnormal patterning of the brain. An increase in severe mental and/or cognitive disorders has been evidenced among children exposed in utero to irradiation doses (0.06 to 0.31 Gy) during Hiroshima and Nagasaki's A-bombings. In this study, we focused on the morphological and molecular variations in neurons after X-irradiation. Image analysis of immuno-stained control compared to irradiated neurons with low and moderate doses (0.1, 0.2 and 0.5 Gy), showed an effect on neurite outgrowth. The main morphological effects were: shortened neurite length, decreased number of neurite per neuron and reduced axonal branching accompanied with down-regulation of pathways involved in cytoskeleton remodelling, necessary for neurite outgrowth. Later on, during the crucial step of synapse formation, neurons underwent neuronal degeneration and apoptosis. This radiation induced cell death appeared to involve an excitotoxicity like phenomenon which might lead to a defect in neuronal network formation and consequently to cognitive disorders.