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Hypergravity Attenuates Reactivity in Primary Murine Astrocytes

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 phenot...

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Autores principales: Lichterfeld, Yannick, Kalinski, Laura, Schunk, Sarah, Schmakeit, Theresa, Feles, Sebastian, Frett, Timo, Herrmann, Harald, Hemmersbach, Ruth, Liemersdorf, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405820/
https://www.ncbi.nlm.nih.gov/pubmed/36009513
http://dx.doi.org/10.3390/biomedicines10081966
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author Lichterfeld, Yannick
Kalinski, Laura
Schunk, Sarah
Schmakeit, Theresa
Feles, Sebastian
Frett, Timo
Herrmann, Harald
Hemmersbach, Ruth
Liemersdorf, Christian
author_facet Lichterfeld, Yannick
Kalinski, Laura
Schunk, Sarah
Schmakeit, Theresa
Feles, Sebastian
Frett, Timo
Herrmann, Harald
Hemmersbach, Ruth
Liemersdorf, Christian
author_sort Lichterfeld, Yannick
collection PubMed
description 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.
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spelling pubmed-94058202022-08-26 Hypergravity Attenuates Reactivity in Primary Murine Astrocytes Lichterfeld, Yannick Kalinski, Laura Schunk, Sarah Schmakeit, Theresa Feles, Sebastian Frett, Timo Herrmann, Harald Hemmersbach, Ruth Liemersdorf, Christian Biomedicines Article 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. MDPI 2022-08-13 /pmc/articles/PMC9405820/ /pubmed/36009513 http://dx.doi.org/10.3390/biomedicines10081966 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lichterfeld, Yannick
Kalinski, Laura
Schunk, Sarah
Schmakeit, Theresa
Feles, Sebastian
Frett, Timo
Herrmann, Harald
Hemmersbach, Ruth
Liemersdorf, Christian
Hypergravity Attenuates Reactivity in Primary Murine Astrocytes
title Hypergravity Attenuates Reactivity in Primary Murine Astrocytes
title_full Hypergravity Attenuates Reactivity in Primary Murine Astrocytes
title_fullStr Hypergravity Attenuates Reactivity in Primary Murine Astrocytes
title_full_unstemmed Hypergravity Attenuates Reactivity in Primary Murine Astrocytes
title_short Hypergravity Attenuates Reactivity in Primary Murine Astrocytes
title_sort hypergravity attenuates reactivity in primary murine astrocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405820/
https://www.ncbi.nlm.nih.gov/pubmed/36009513
http://dx.doi.org/10.3390/biomedicines10081966
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