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

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

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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.

Original languageEnglish
Article number4094
Number of pages16
JournalInternational journal of molecular sciences
Volume20
Issue number17
DOIs
Publication statusPublished - 22 Aug 2019

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Overbey, E. G., Paul, A. M., da Silveira, W. A., Tahimic, C. G. T., Reinsch, S. S., Szewczyk, N., Stanbouly, S., Wang, C., Galazka, J. M., & 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), [4094]. https://doi.org/10.3390/ijms20174094