Astrocyte reactivity as a novel biomarker for combined effects of ionizing radiation and simulated microgravity

Abstract

During their missions in space, astronauts are exposed to weightlessness and increased doses of radiation. Consequences for their stay in space can include cognitive decline or depression. In response to impairment of the central nervous system, astrocytes can express a reactive phenotype. They can have either beneficial or detrimental effects on the surrounding tissue. After irradiation of rats and mice, studies showed that astrocytes changed their phenotypic behaviour and became reactive. Astronauts are exposed to increased radiation as well as weightlessness during space missions. Aim of this thesis is to investigate the effects of simulated space conditions, i.e., ionizing irradiation in combination with simulated weightlessness on astrocytes as a model system relevant for human space exploration missions. The current study was conducted by exposing primary murine astrocytes to a combination of different doses of X-irradiation and varying exposure times of simulated weightlessness. Effects were assessed by immunostaining with several astrocytic reactivity and DNA damage markers. In order to get insights into a differential gene expression profile in future studies, six genes were tested for their suitability as housekeeping genes in studies combining X-irradiation and simulated weightlessness. The results did not indicate a transition of astrocytes into a reactive state in any condition. Furthermore, no significant influence of simulated weightlessness on DNA damage could be detected, but there is a tendency towards less damage after simulated weightlessness. Due to variability in expression of housekeeping genes, it was not possible to draw clear conclusions regarding their suitability as validation for use in studies combining X-irradiation and simulated weightlessness. Results obtained here do not indicate that astrocytes exhibit a reactive phenotype when treated with X-irradiation followed by simulated weightlessness. This study contributes to understand how simulated space conditions effect astroglia. Astrocytes in pure culture are largely unaffected by X-irradiation and simulated weightlessness, they do not exhibit a reactive phenotype. Since reactive astrocytes can also have beneficial consequences, further research could reveal opportunities to target astrocyte reactivity to counteract the negative consequences of space missions.