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Unraveling astrocyte behavior in the space brain: Radiation response of primary astrocytes

Roggan, Marie Denise and Kronenberg, Jessica and Wollert, Esther Katharina and Hoffmann, Sven and Nisar, Hasan and Konda, Bikash and Diegeler, Sebastian and Liemersdorf, Christian and Hellweg, Christine Elisabeth (2023) Unraveling astrocyte behavior in the space brain: Radiation response of primary astrocytes. Frontiers in Public Health, 11, p. 1063250. Frontiers Media S.A.. doi: 10.3389/fpubh.2023.1063250. ISSN 2296-2565.

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Official URL: https://dx.doi.org/10.3389/fpubh.2023.1063250

Abstract

Introduction: Exposure to space conditions during crewed long-term exploration missions can cause several health risks for astronauts. Space radiation, isolation and microgravity are major limiting factors. The role of astrocytes in cognitive disturbances by space radiation is unknown. Astrocytes' response toward low linear energy transfer (LET) X-rays and high-LET carbon (¹²C) and iron (⁵⁶Fe) ions was compared to reveal possible effects of space-relevant high-LET radiation. Since astronauts are exposed to ionizing radiation and microgravity during space missions, the effect of simulated microgravity on DNA damage induction and repair was investigated. Methods: Primary murine cortical astrocytes were irradiated with different doses of X-rays, ¹²C and ⁵⁶Fe ions at the heavy ion accelerator GSI. DNA damage and repair (γH2AX, 53BP1), cell proliferation (Ki-67), astrocytes' reactivity (GFAP) and NF-κB pathway activation (p65) were analyzed by immunofluorescence microscopy. Cell cycle progression was investigated by flow cytometry of DNA content. Gene expression changes after exposure to X- rays were investigated by mRNA-sequencing. RT-qPCR for several genes of interest was performed with RNA from X-rays- and heavy-ion-irradiated astrocytes: Cdkn1a, Cdkn2a, Gfap, Tnf, Il1β, Il6, and Tgfβ1. Levels of the pro inflammatory cytokine IL-6 were determined using ELISA. DNA damage response was investigated after exposure to X-rays followed by incubation on a 2D clinostat to simulate the conditions of microgravity. Results: Astrocytes showed distinct responses toward the three different radiation qualities. Induction of radiation-induced DNA double strand breaks (DSBs) and the respective repair was dose-, LET- and time-dependent. Simulated microgravity had no significant influence on DNA DSB repair. Proliferation and cell cycle progression was not affected by radiation qualities examined in this study. Astrocytes expressed IL-6 and GFAP with constitutive NF-κB activity independent of radiation exposure. mRNA sequencing of X-irradiated astrocytes revealed downregulation of 66 genes involved in DNA damage response and repair, mitosis, proliferation and cell cycle regulation. Discussion: In conclusion, primary murine astrocytes are DNA repair proficient irrespective of radiation quality. Only minor gene expression changes were observed after X-ray exposure and reactivity was not induced. Co-culture of astrocytes with microglial cells, brain organoids or organotypic brain slice culture experiments might reveal whether astrocytes show a more pronounced radiation response in more complex network architectures in the presence of other neuronal cell types.

Item URL in elib:https://elib.dlr.de/194749/
Document Type:Article
Title:Unraveling astrocyte behavior in the space brain: Radiation response of primary astrocytes
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iDORCID Put Code
Roggan, Marie DeniseGerman Center for Neurodegenerative Diseases, Helmholtz Association of German Research Centers (HZ) Bonn, Germany and Radiation Biology Department, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Kronenberg, JessicaMicrogravity User Support Center (MUSC), German Aerospace Center (DLR), Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Wollert, Esther KatharinaRadiation Biology Department, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany and Structural Biochemistry (IBI-7), Institute of Biological Information Processing (IBI), Forschungszentrum Jülich GmbH, Jülich, GermanyUNSPECIFIEDUNSPECIFIED
Hoffmann, SvenDepartment of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany and Department of Gravitational Biology, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Nisar, HasanDepartment of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany and Department of Medical Sciences, Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad, PakistanUNSPECIFIEDUNSPECIFIED
Konda, BikashDepartment of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, GermanyUNSPECIFIEDUNSPECIFIED
Diegeler, SebastianDepartment of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany and Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, United Stateshttps://orcid.org/0000-0003-3161-0744UNSPECIFIED
Liemersdorf, ChristianUNSPECIFIEDhttps://orcid.org/0000-0001-8407-5226UNSPECIFIED
Hellweg, Christine ElisabethUNSPECIFIEDhttps://orcid.org/0000-0002-2223-3580UNSPECIFIED
Date:6 April 2023
Journal or Publication Title:Frontiers in Public Health
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:11
DOI:10.3389/fpubh.2023.1063250
Page Range:p. 1063250
Publisher:Frontiers Media S.A.
ISSN:2296-2565
Status:Published
Keywords:astrocytes, X-rays, heavy ions, simulated microgravity, DNA double strand breaks, cytokines, cell cycle, astrocyte reactivity
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 - NeuroSpace
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Radiation Biology
Institute of Aerospace Medicine > Gravitational Biology
Space Operations and Astronaut Training > User center for space experiments (MUSC)
Deposited By: Kopp, Kerstin
Deposited On:27 Apr 2023 11:19
Last Modified:12 May 2023 13:37

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