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

• Published in: International journal of molecular sciences 2019-08, Vol.20 (17), p.4094
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Aquaporin 4; Aquaporins; Astronauts; Biomarkers; Blood-brain barrier; Body Weight; Brain; Brain - metabolism; Brain - physiopathology; Brain damage; Brain injury; Central nervous system; chronic low-dose irradiation; Design of experiments; Disease Models, Animal; Disease Susceptibility; DNA Methylation; Environmental Exposure - adverse effects; Exposure; Female; Females; Gamma Rays; Gene expression; Gene Expression Profiling; Gravity; hindlimb unloading; Homeostasis; Hyperactivity; Mice; Nervous system; Nervous System Diseases - etiology; Nervous System Diseases - metabolism; Neurogenesis; Neurological complications; Neuropeptides; Neuroplasticity; NMR; Nuclear magnetic resonance; Ontology; Oxidative stress; Principal components analysis; Promoter Regions, Genetic; Radiation; Radiation Dosage; Radiation, Ionizing; Signal Transduction; Space flight; Space missions; Tight junctions; Transcriptome; Weightlessness; Weightlessness Simulation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20174094

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.