Ionizing radiation induced transcriptional changes in the developing mouse brain

Brain damage induced by prenatal irradiation is of major concern in radioprotection. The brain is the final result of a series of well timed consecutive waves of cellular proliferation, migration, and differentiation. Acute irradiation during pregnancy could selectively disturb these events to result in various forms of malformations such as microencephaly, reduced cortical thickness, glioblastoma tumours and/or mental retardation. In this work we concentrated on the transcriptional alterations induced by ionising radiation in the mouse developing brain and its different cell-types. This work can be subdivided into four parts. In a first part the transcriptional response to ionising radiation was evaluated in the developing brain, with emphasis on the central role of the Trp53 oncogene. To determine possible regional differences we evaluated the radiation induced transcriptional response in three different regions of the telencepehalon. Since cell type dependent differences can be observed after radiation exposure, we evaluated the neural celltype and differentiation-stage dependent radiation induced transcriptional and cellular responses. Finally to examine other not cell death related cellular response the effect of ionising radiation on neurite outgrowth was studied.