Changes in astrocytic behavior induced by altered gravity

Abstract

After CNS injuries, neural regeneration and remyelination are inhibited, inter alia, by the formation of the glial scar. Although it prevents the widespread of damaged tissue, it is also preventing axon regrowth and therefore the healing of a CNS injury, leading to major and long-lasting or persistent restrictions. As soon as the mechanisms of this process are explored, possible therapeutic approaches to influence this process will be achievable. As astrocytes play an important role in the process of the formation of the glial scar, it is also essential to understand the mechanisms of the shift between their predominant non-reactive state and the reactive state following injury, as well as to find a way to reliably identify reactive astrocytes within the cell population. Previous studies have shown that astrocytes exposed to hypergravity in the physiological range (2 g) exhibited decreased cell spreading and migration rates in comparison to 1 g control samples. Furthermore, in contrast to astrocytes, neurons increase their neurite numbers as well as their neurite projection lengths under the influence of 2 g. Therefore, gravity might play an essential role in achieving possible therapeutic approaches to influence the formation of the glial scar. The aim of this thesis was to further investigate these promising results, focusing on the effects of hypergravity on key cellular parameters of primary murine astrocytes. These key parameters included apoptosis and necrosis, proliferation, reactivity, and morphology. Over the timespan of 120 h, for each parameter one assay was conducted, comparing 2 g samples with the 1 g control samples. Another important part of this thesis was to develop a measurable scoring approach to assess astrocyte reactivity, identifying if astrocytes are reactive, and subsequently in which state of reactivity they exist. This will build a base for further studies on astrocyte behavior under normal and altered gravity conditions. Overall, this study contributes to understanding the effects of hypergravity that is employed as a tool to specifically alter key astrocytic parameters, and thus influencing and possibly inhibiting the formation of a glial scar. Therefore, helping to find possible regeneration strategies, ideally, a regeneration method which induces a slower formation of a glial scar without the loss of the positive natural attributes could be developed.