Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae
Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model: s...
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doaj-f4b2763c163c4c808fab6584b30ed1502020-11-25T01:02:57ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-08-012017409410.3390/ijms20174094ijms20174094Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological SequelaeEliah G. Overbey0Amber M. Paul1Willian A. da Silveira2Candice G.T. Tahimic3Sigrid S. Reinsch4Nathaniel Szewczyk5Seta Stanbouly6Charles Wang7Jonathan M. Galazka8Xiao Wen Mao9Department of Genome Sciences, University of Washington, Seattle, WA 98195, USASpace Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USAInstitute for Global Food Security (IGF), School of Biological Sciences, Queen’s University, Belfast, Northern Ireland BT7 1NN, UKSpace Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USASpace Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USAMRC/ARUK Centre for Musculoskeletal Ageing Research & National Institute for Health Research Nottingham Biomedical Research Centre, Royal Derby Hospital, University of Nottingham, Derby DE22 3DT, UKDivision of Biomedical Engineering Sciences (BMES), Department of Basic Sciences, Loma Linda University, Loma Linda, CA 92354, USACenter for Genomics, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USASpace Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USADivision of Biomedical Engineering Sciences (BMES), Department of Basic Sciences, Loma Linda University, Loma Linda, CA 92354, USASpaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model: simulated microgravity via hindlimb unloading (HLU) and/or low-dose γ-ray irradiation (LDR) for 21 days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in brain samples during readaptation were analyzed by whole transcriptome shotgun sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression and cytosine methylation alterations at 4 months readaptation within single treatment conditions of HLU or LDR. In contrast, following combined HLU+LDR, gene expression and promoter methylation analyses showed multiple altered pathways involved in neurogenesis and neuroplasticity, the regulation of neuropeptides, and cellular signaling. In brief, neurological readaptation following combined chronic LDR and HLU is a dynamic process that involves pathways that regulate neuronal function and structure and may lead to late onset neurological sequelae.https://www.mdpi.com/1422-0067/20/17/4094hindlimb unloadingchronic low-dose irradiationbraintranscriptome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eliah G. Overbey Amber M. Paul Willian A. da Silveira Candice G.T. Tahimic Sigrid S. Reinsch Nathaniel Szewczyk Seta Stanbouly Charles Wang Jonathan M. Galazka Xiao Wen Mao |
spellingShingle |
Eliah G. Overbey Amber M. Paul Willian A. da Silveira Candice G.T. Tahimic Sigrid S. Reinsch Nathaniel Szewczyk Seta Stanbouly Charles Wang Jonathan M. Galazka Xiao Wen Mao Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae International Journal of Molecular Sciences hindlimb unloading chronic low-dose irradiation brain transcriptome |
author_facet |
Eliah G. Overbey Amber M. Paul Willian A. da Silveira Candice G.T. Tahimic Sigrid S. Reinsch Nathaniel Szewczyk Seta Stanbouly Charles Wang Jonathan M. Galazka Xiao Wen Mao |
author_sort |
Eliah G. Overbey |
title |
Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae |
title_short |
Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae |
title_full |
Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae |
title_fullStr |
Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae |
title_full_unstemmed |
Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae |
title_sort |
mice exposed to combined chronic low-dose irradiation and modeled microgravity develop long-term neurological sequelae |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-08-01 |
description |
Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model: simulated microgravity via hindlimb unloading (HLU) and/or low-dose γ-ray irradiation (LDR) for 21 days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in brain samples during readaptation were analyzed by whole transcriptome shotgun sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression and cytosine methylation alterations at 4 months readaptation within single treatment conditions of HLU or LDR. In contrast, following combined HLU+LDR, gene expression and promoter methylation analyses showed multiple altered pathways involved in neurogenesis and neuroplasticity, the regulation of neuropeptides, and cellular signaling. In brief, neurological readaptation following combined chronic LDR and HLU is a dynamic process that involves pathways that regulate neuronal function and structure and may lead to late onset neurological sequelae. |
topic |
hindlimb unloading chronic low-dose irradiation brain transcriptome |
url |
https://www.mdpi.com/1422-0067/20/17/4094 |
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