Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart

Abstract

PurposeSpace travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation.MethodsCardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group.ResultsThe combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen.ConclusionsThis study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and cardiac remodeling in response to HU with simultaneous exposure to low-dose rate γ-radiation. Results from the late observation time points suggest that the hearts had mostly recovered from these two experimental conditions. However, further research is needed with larger numbers of animals for a more robust statistical power to fully characterize the early and late effects of simulated microgravity combined with exposure to low-dose rate ionizing radiation on the heart.

Sex-Specific Cognitive Deficits Following Space Radiation Exposure

“…Radiation-induced cognitive dysfunction is a multifaceted disorder caused by elevated oxidative stress, neuroinflammation, declines in neurogenesis, and a degradation of neuronal structure and synaptic integrity (Poulose et al, 2014;Tseng et al, 2014;Allen et al, 2015;Parihar et al, 2015bParihar et al, , 2018Acharya et al, 2016;Seawright et al, 2017;Carr et al, 2018;Hinkle et al, 2019). While many mechanisms influence these dynamic processes, microglia play an active role in reshaping the connective landscape of the brain by selectively pruning dendritic architecture and synapses in the irradiated or otherwise compromised brain (Lumniczky et al, 2017;Krukowski et al, 2018b;Rosi, 2018;Hinkle et al, 2019;Liu et al, 2019).…”

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

“…During missions beyond low-earth orbit (LEO), astronauts will be continuously exposed to low-dose ionizing radiation (LDR). While high linear energy transfer (LET) galactic cosmic radiation (GCR) and low LET solar particle event (SPE) radiation contribute large portions of the radiation dose accumulated by astronaut crew members [3], interactions between GCR and SPE particles and spacecraft release secondary radiation including γ-rays that can deliver a significant fraction of the total mission does [4]. In addition, altered gravity (hypergravity experienced at launch/landing and microgravity experienced in-flight) affects homeostatic fluid-shifting in the CNS.…”

Simulated Weightlessness Perturbs the Intestinal Metabolomic Profile of Rats

“…In the present study, it was found that simulated weightlessness remarkably decreased the amount of sinapinic acid, 4-hydroxypyridine and indolelactate, which suggested the high oxidative status and oxidative stress within the intestinal tract that might contribute to the inflammation and breakdowns of intestinal homeostasis. Some literature has reported oxidative bursts under space environments and simulated microgravity or weightlessness conditions (Yamauchi et al, 2002; Jayroe et al, 2012; Seawright et al, 2017; Pavlakou et al, 2018). Mechanisms of interactions between intestinal microbiota metabolites and oxidative stress-induced intestinal dysfunction under microgravity need to be further investigated.…”