Hypergravity Attenuates Reactivity in Primary Murine Astrocytes

Abstract

Neuronal activity is the key modulator of nearly every aspect of behavior, affecting cognition, learning, and memory as well as motion. Hence, disturbances of the transmission of synaptic signals are the main cause of many neurological disorders. Lesions to nervous tissues are associated with phenotypic changes mediated by astrocytes becoming reactive. Reactive astrocytes form the basis of astrogliosis and glial scar formation. Astrocyte reactivity is often targeted to inhibit axon dystrophy and thus promote neuronal regeneration. Here, we aim to understand the impact of gravitational loading induced by hypergravity to potentially modify key features of astrocyte reactivity. We exposed primary murine astrocytes as a model system closely resembling the in vivo reactivity phenotype on custom-built centrifuges for cultivation as well as for live-cell imaging under hypergravity conditions in a physiological range (2g and 10g). We revealed spreading rates, migration velocities, and stellation to be diminished under 2g hypergravity. In contrast, proliferation and apoptosis rates were not affected. In particular, hypergravity attenuated reactivity induction. We observed cytoskeletal remodeling of actin filaments and microtubules under hypergravity. Hence, the reorganization of these key elements of cell structure demonstrates that fundamental mechanisms on shape and mobility of astrocytes are affected due to altered gravity conditions. In future experiments, potential target molecules for pharmacological interventions that attenuate astrocytic reactivity will be investigated. The ultimate goal is to enhance neuronal regeneration for novel therapeutic approaches.

Translation from Microgravity Research to Earth Application

“…The topic “Translation from Microgravity Research to Earth Application” comprises publications focusing on space life sciences, gravitational biology and space medicine [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. It covers publications reporting the impact of altered environmental conditions, such as microgravity (µ g ), cosmic radiation and isolation on organisms down to the level of cells [ 3 , 4 , 5 , 7 , 8 , 10 , 11 , 12 , 13 , 14 ].…”

“…It covers publications reporting the impact of altered environmental conditions, such as microgravity (µ g ), cosmic radiation and isolation on organisms down to the level of cells [ 3 , 4 , 5 , 7 , 8 , 10 , 11 , 12 , 13 , 14 ]. In addition, the topic collects studies validating causal diagrams of human health risks for spaceflight [ 1 ], hypergravity studies [ 2 ] and investigations about the impact of extreme isolation in the Antarctica on the human body [ 6 ].…”

“…Two research articles focused on neurological changes induced by altered gravity conditions [ 2 , 12 ]. An in vitro study evaluated the impact of hypergravity to potentially modify key features of astrocyte reactivity [ 2 ].…”

“…Two research articles focused on neurological changes induced by altered gravity conditions [ 2 , 12 ]. An in vitro study evaluated the impact of hypergravity to potentially modify key features of astrocyte reactivity [ 2 ]. Fundamental mechanisms on shape and mobility of astrocytes are affected due to increased gravitational stimulation (hypergravity).…”

“…Lichterfeld et al identified an attenuation of key features of astrocyte reactivity due to hypergravity exposure. This finding suggests hypergravity together with live-cell imaging as a tool for future studies with other cell types, organoids, 3D spheroids or ex vivo cultures [ 2 ]. The second neurological study used the hindlimb unloading model (HLU) to expose rats to s-µ g for seven days and focused on the distribution of monoamines in functional territories of the rat brain [ 12 ].…”