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Response of primary astrocytes to ionizing radiation exposure

Roggan, Marie Denise and Kronenberg, Jessica and Wollert, Esther and Hoffmann, Sven and Nisar, Hasan and Konda, Bikash and Diegeler, Sebastian and Liemersdorf, Christian and Hellweg, Christine Elisabeth (2023) Response of primary astrocytes to ionizing radiation exposure. DeGBS Jahrestagung 2023, 2023-09-18 - 2023-09-20, Hohenwart, Deutschland.

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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 towards 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. 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 the genes of interest was performed with 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. Results: Astrocytes showed distinct responses towards the three different radiation qualities. Induction of radiation-induced DNA double strand breaks (DSB) and the respective repair was dose-, LET- and time-dependent. Proliferation and cell cycle progression were 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. 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. Acknowledgement: We thank our liaison scientists at GSI, Insa Schröder and Denise Eckart, for their excellent technical assistance in preparation of and during the beamtimes. Ulrich Weber and Thomas Friedrich at GSI are acknowledged for their dedicated and precise irradiation of our samples at GSI. Our thanks also go to the beam operators at GSI for operating the accelerator during our experiments.

Item URL in elib:https://elib.dlr.de/197309/
Document Type:Conference or Workshop Item (Poster)
Title:Response of primary astrocytes to ionizing radiation exposure
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iDORCID Put Code
Roggan, Marie DeniseRadiation Biology Department, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany and Current address: Institute for Neuropathology, University Clinics Essen, GermanyUNSPECIFIEDUNSPECIFIED
Kronenberg, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wollert, EstherRadiation Biology Department, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany and Current address: Forschungszentrum Jülich, Jülich, GermanyUNSPECIFIEDUNSPECIFIED
Hoffmann, SvenRadiation Biology Department, 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, HasanRadiation Biology Department, 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, BikashRadiation Biology Department, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIEDUNSPECIFIED
Diegeler, SebastianRadiation Biology Department, German Aerospace Center (DLR), Institute of Aerospace Medicine, Cologne and Department of Radiation Oncology, Harold C. Simmons Comprehensive Cancer Center, U.T. Southwestern Medical Center, Dallas, TX, USAUNSPECIFIEDUNSPECIFIED
Liemersdorf, ChristianUNSPECIFIEDhttps://orcid.org/0000-0001-8407-5226UNSPECIFIED
Hellweg, Christine ElisabethUNSPECIFIEDhttps://orcid.org/0000-0002-2223-3580UNSPECIFIED
Date:18 September 2023
Refereed publication:Yes
Open Access:No
Gold Open Access:No
In SCOPUS:No
In ISI Web of Science:No
Status:Published
Keywords:primary astrocytes, ionizing radiation exposure, NF-κB
Event Title:DeGBS Jahrestagung 2023
Event Location:Hohenwart, Deutschland
Event Type:national Conference
Event Start Date:18 September 2023
Event End Date:20 September 2023
Organizer:DeGBS
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 Sep 2023 10:27
Last Modified:24 Apr 2024 20:57

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