Regulation of immune cells in the periphery and central nervous system after X-ray irradiation

Abstract

Space environment presents great danger for astronauts' health. One of the major risk factors is exposure to ionizing radiation, which has the potential to ionize atoms and molecules. This can have detrimental effects to cellular mechanisms as well as the biological systems as a whole. Due to the overlap of different biological systems it is impossible to study them individually. Two important organ systems severely affected by ionizing radiation are the immune system and the central nervous system (CNS). The role of irradiated immune cells of the CNS in the pathogenesis of cognitive deficits in addition to those caused by radiation exposure of neuronal cells still needs to be elucidated. The aim of this thesis was to understand the response of microglia with an activated or an inactivated phenotype to different doses of X-irradiation. The murine BV-2 cell line was used as model for microglial cells. DNA damage, apoptotic activity and phagocyic rates after irradiation were determined. For comparison, DNA double strand breaks (DSB) were also measured in the monocyte cell line (U937) after irradiation. While X-irradiation caused a dosedependent increase in DSB, no significant induction of apoptosis or reduction of phagocytotic activity was observed. The responses were comparable for inactivated and activated microglia with an exception of significant results observed in the amount of DNA DSB after irradiation with a dose of 4 Gy. A trend of decreased phagocitic activity was observed in both activated and inactivated phenotype 24 hours post irradiation for the dose of 4 Gy, but did not yield a significant result. The radiation-induced effects 24-hours post irradiation decreased in comparison to the 1- hour post irradiation timepoint which entails the efficiency of the repair mechanisms. Further experiments should be done in order to truly understand the implications of the activated and inactivated phenotype as well as the X-irradiation dose effects on the immune cells of the CNS and the resulting neurological damage or protection.