Exposure to high doses of ionizing radiation is known to have detrimental effects on human health. From epidemiological data obtained from atomic bomb survivors, there were indications that exposure does not only cause an increase in cancer occurrence, but also affects brain development when exposed in utero between weeks 8-25 of human gestation. At the long term, this leads to persistent defects such as mental retardation, and might also induce visual impairments, as was suggested in prenatally irradiated mice. In this thesis we investigated the short- and long-term effects of irradiation during this radiosensitive time period. To achieve this, we irradiated mice with 1.00 and 0.10 Gy at embryonic day 11, corresponding to week 8 of human gestation, and looked at radiation-induced effects at 6 h and 24 h post-irradiation (PI) as well as at postnatal day 10. This showed that DNA damage was still apparent at 6 h PI after 1.00 Gy, which was accompanied by cell death until 24 h PI. Next, we quantified the number of neural stem cells, since they play a crucial role in brain development, which revealed a reduction in stem cells and a concurrent increase in postmitotic neurons after irradiation. This, together with additional immunohistochemical analyses, led to the hypothesis of a premature neuronal differentiation, which is probably caused by an accelerated transition out of the ventricular zone. This hypothesis could also explain our observation of a decreased postnatal brain weight and thickness of the visual cortex, all supportive for a radiation-induced microcephaly phenotype.
|Qualification||Master of Science|
|Date of Award||6 Jul 2017|
|State||Published - 14 Jun 2017|