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Hypergravity Reduces Astrocyte Migration by Altering Cytoskeletal Dynamics

Liemersdorf, Christian and Lichterfeld, Yannick and Kalinski, Laura and Frett, Timo and Jordan, Jens and Hemmersbach, Ruth (2020) Hypergravity Reduces Astrocyte Migration by Altering Cytoskeletal Dynamics. FASEB JOURNAL, 34 (S1). Federation of American Societies for Experimental Biology. doi: 10.1096/fasebj.2020.34.s1.02872. ISSN 0892-6638.

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Glial scar formation through astrocytes impairs neural regeneration following spinal cord injury, head trauma, or stroke. Astrocyte migration towards the lesion and induction of a reactive astroglial phenotype require dynamic cytoskeletal protein rearrangements. In this glial cell model, hypergravity was used to alter cytoskeletal dynamics, i.e. stabilizing microtubules while destabilizing actin filaments. We hypothesize that increased gravitational (mechanical) loading by means of centrifugation (hypergravity) modulates in vitro astrocyte function in a way that could reduce their potential for scar formation. We exposed primary murine cortical astrocytes to 2g using two types of custom-designed hypergravity platforms at DLR (Cologne, Germany) and assessed a variety of parameters important for glial scarring in vitro. The platforms unlike commercial laboratory centrifuges model physiological hypergravity and allow for cell cultivation and live-cell imaging. Primary astrocytes were isolated from wildtype (C57BL/6J) as well as transgenic LifeAct-GFP mice and subjected to increased gravitational load. We measured cell proliferation and survival, after 7 days of exposure to 2g, as well as spreading and migration rate online for 24h. We visualized morphological features, cytoskeletal actin filament dynamics, reactivity markers and investigated expression levels of focal adhesion-related proteins. The exposure to 2g hypergravity induced a decrease in cell spreading (20%) coincidental with an inhibited migratory behavior (40%) and altered cytoskeletal dynamics. Astrocytic proliferation and survival were not affected. The expression of the focal adhesion marker vinculin was increased by 70–80%. We conclude that hypergravity attenuates astrocyte spreading and migration. These parameters are crucial for glial scar formation, while basic cellular processes, such as proliferation and apoptosis were unchanged. The response appears to be mediated through altered cytoskeletal dynamics and may provide targets for therapies promoting neuronal regeneration.

Item URL in elib:https://elib.dlr.de/185770/
Document Type:Article
Title:Hypergravity Reduces Astrocyte Migration by Altering Cytoskeletal Dynamics
AuthorsInstitution or Email of AuthorsAuthor's ORCID iDORCID Put Code
Liemersdorf, ChristianUNSPECIFIEDhttps://orcid.org/0000-0001-8407-5226UNSPECIFIED
Lichterfeld, YannickUNSPECIFIEDhttps://orcid.org/0000-0001-8755-9920UNSPECIFIED
Kalinski, LauraUNSPECIFIEDhttps://orcid.org/0009-0009-4447-3460UNSPECIFIED
Frett, TimoUNSPECIFIEDhttps://orcid.org/0000-0002-5572-1177UNSPECIFIED
Jordan, JensUNSPECIFIEDhttps://orcid.org/0000-0003-4518-0706UNSPECIFIED
Date:17 April 2020
Journal or Publication Title:FASEB JOURNAL
Refereed publication:Yes
Open Access:No
Gold Open Access:No
In ISI Web of Science:Yes
Publisher:Federation of American Societies for Experimental Biology
Keywords:Hypergravity; Astrocyte; Cytoskeletal Dynamic
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Human performance under altered gravity conditions
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Gravitational Biology
Deposited By: Becker, Christine
Deposited On:11 Apr 2022 10:20
Last Modified:20 Oct 2023 09:03

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