Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae

Overbey, Eliah G.; Paul, Amber M.; da Silveira, Willian A.; Tahimic, Candice G.T.; Reinsch, Sigrid S.; Szewczyk, Nathaniel; Stanbouly, Seta; Wang, Charles; Galazka, Jonathan M.; Mao, Xiao Wen

Abstract

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.

Citation

Overbey, E. G., Paul, A. M., da Silveira, W. A., Tahimic, C. G., Reinsch, S. S., Szewczyk, N., …Mao, X. W. (2019). Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae. International Journal of Molecular Sciences, 20(17), Article 4094. https://doi.org/10.3390/ijms20174094

• Journal Article Type: Article
• Acceptance Date: Aug 9, 2019
• Online Publication Date: Aug 22, 2019
• Publication Date: Aug 22, 2019
• Deposit Date: Aug 26, 2019
• Publicly Available Date: Aug 27, 2019
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 17
• Article Number: 4094
• DOI: https://doi.org/10.3390/ijms20174094
• Keywords: Hindlimb unloading; Chronic low-dose irradiation; Brain; Transcriptome
• Public URL: https://nottingham-repository.worktribe.com/output/2502951
• Publisher URL: https://www.mdpi.com/1422-0067/20/17/4094