Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae
Human Factors and Behavioral Neurobiology
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.
International Journal of Molecular Sciences
Grant or Award Name
y NASA grant No. 80NSSC17K0693 and NNX13AL97G, GeneLab Project, NASA Space Biology Program, BBSRC (BB/N015894/1), NIHR Nottingham Biomedical Research Centre, (NIH) grant S10OD019960, h (AIH) grant 2150141, Charles A. Sims’ gift
Scholarly Commons Citation
Paul, A. M., Overbey, E. G., da Silveira, W. A., Tahimic, C. G., 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(4094). http://dx.doi.org/10.3390/ijms20174094
Molecular and Cellular Neuroscience Commons, Neurology Commons, Radiation Medicine Commons
Dr. Paul was not affiliated with Embry-Riddle Aeronautical University at the time this paper was published.