The impact of deep space radiation on cognitive performance: From biological sex to biomarkers to countermeasures

Grue, Katherine; Becker, McKenna; Elizarraras, Edward; Frias, Elma S.; Halvorsen, Aaron; Koenig-Zanoff, McKensie; Frattini, Valentina; Nimmagadda, Hasitha; Feng, Xi; Jones, Tamako; Nelson, Gregory A.; Ferguson, Adam R.; Rosi, Susanna

doi:10.1126/sciadv.abg6702

Cited by 31 publications

(43 citation statements)

References 42 publications

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“…Finally, we uncovered multiple gene and pathway-level associations between radiationinduced DNA damage and the nervous system. Ionizing radiation is a major neurotoxic factor: high-LET particles have been shown to cause neuroinflammation, neurodegeneration and behavioral deficits in inbred C57BL/6J and transgenic Tg(Thy1-EGFP) MJrsJ mice (PARIHAR et al 2016;KRUKOWSKI et al 2021). However, our results suggest that different mouse strains might not be equally susceptible to ionizing radiation-induced neurotoxicity.…”

Section: Comparing Responses To High and Low Let Radiationcontrasting

confidence: 54%

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Mouse Genomic Associations withEx VivoSensitivity to Simulated Space Radiation

Cekanaviciute

Tran

Nguyen

et al. 2022

Preprint

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Exposure to ionizing radiation is considered by NASA to be a major health hazard for deep space exploration missions. Ionizing radiation sensitivity is modulated by both genomic and environmental factors. Understanding their contributions is crucial for designing experiments in model organisms, evaluating the risk of deep space (i.e. high-linear energy transfer, or LET, particle) radiation exposure in astronauts, and also selecting therapeutic irradiation regimes for cancer patients. We identified single nucleotide polymorphisms in 15 strains of mice, including 10 collaborative cross model strains and 5 founder strains, associated with spontaneous and ionizing radiation-induced ex vivo DNA damage quantified based on immunofluorescent 53BP1+ nuclear foci. Statistical analysis suggested an association with pathways primarily related to cellular signaling, metabolism, tumorigenesis and nervous system damage. We observed different genomic associations in early (4 and 8 hour) responses to different LET radiation, while later (24 hour) DNA damage responses showed a stronger overlap across all LETs. Furthermore, a subset of pathways was associated with spontaneous DNA damage, suggesting 53BP1+ foci as a potential biomarker for DNA integrity in mouse models. Based on our results, we suggest several mouse strains as new models to further study the impact of ionizing radiation and validate the identified genetic loci. We also highlight the importance of future human ex vivo studies to refine the association of genes and pathways with the DNA damage response to ionizing radiation and identify targets for space travel countermeasures.

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Section: Comparing Responses To High and Low Let Radiationcontrasting

confidence: 54%

“…Ionizing radiation is a major neurotoxic factor: high-LET particles have been shown to cause neuroinflammation, neurodegeneration and behavioral deficits in inbred C57BL/6J and transgenic Tg(Thy1-EGFP) MJrsJ mice (P arihar et al . 2016; K rukowski et al . 2021).…”

Section: Resultsmentioning

confidence: 99%

Mouse Genomic Associations withEx VivoSensitivity to Simulated Space Radiation

Cekanaviciute

Tran

Nguyen

et al. 2022

Preprint

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“…The experimental design is depicted in Figure 2 . These particles were selected due to their major biological effects on rodent CNS in vivo ( 24 – 26 ) combined with a gap in knowledge regarding their functions in human CNS and the associated blood-brain barrier effects in either animal or human models.…”

Section: Resultsmentioning

confidence: 99%

Astrocytes regulate vascular endothelial responses to simulated deep space radiation in a human organ-on-a-chip model

et al. 2022

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Central nervous system (CNS) damage by galactic cosmic ray radiation is a major health risk for human deep space exploration. Simulated galactic cosmic rays or their components, especially high Z-high energy particles such as 56Fe ions, cause neurodegeneration and neuroinflammation in rodent models. CNS damage can be partially mediated by the blood-brain barrier, which regulates systemic interactions between CNS and the rest of the body. Astrocytes are major cellular regulators of blood-brain barrier permeability that also modulate neuroinflammation and neuronal health. However, astrocyte roles in regulating CNS and blood-brain barrier responses to space radiation remain little understood, especially in human tissue analogs. In this work, we used a novel high-throughput human organ-on-a-chip system to evaluate blood-brain barrier impairments and astrocyte functions 1-7 days after exposure to 600 MeV/n 56Fe particles and simplified simulated galactic cosmic rays. We show that simulated deep space radiation causes vascular permeability, oxidative stress, inflammation and delayed astrocyte activation in a pattern resembling CNS responses to brain injury. Furthermore, our results indicate that astrocytes have a dual role in regulating radiation responses: they exacerbate blood-brain barrier permeability acutely after irradiation, followed by switching to a more protective phenotype by reducing oxidative stress and pro-inflammatory cytokine and chemokine secretion during the subacute stage.

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“…Moreover, the use of whole-body irradiation to facilitate bone marrow engraftment leads to long-term and brain-wide cognitive and synaptic deficits [ 45 ]. Indeed, cognizant of the gamut of stressors that accompany deep space travels, (including ionizing radiation, gravitational changes during flight and in orbit, psychological stress from a confined environment and social isolation) galactic cosmic radiation exposure represents the most dangerous of stressors [ 46 , 47 ]. Each deep spaceflight stressor, or a combination thereof, may represent unique circulating immune responses coupled with an altered immune system, as evidenced by circulating plasma microRNA sequence analysis [ 48 ].…”

Section: Inflammation-plagued Tbi-like Eventsmentioning

confidence: 99%

Stem Cell Therapy for Sequestration of Traumatic Brain Injury-Induced Inflammation

Borlongan

Rosi

2022

IJMS

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Traumatic brain injury (TBI) is one of the leading causes of long-term neurological disabilities in the world. TBI is a signature disease for soldiers and veterans, but also affects civilians, including adults and children. Following TBI, the brain resident and immune cells turn into a “reactive” state, characterized by the production of inflammatory mediators that contribute to the development of cognitive deficits. Other injuries to the brain, including radiation exposure, may trigger TBI-like pathology, characterized by inflammation. Currently there are no treatments to prevent or reverse the deleterious consequences of brain trauma. The recognition that TBI predisposes stem cell alterations suggests that stem cell-based therapies stand as a potential treatment for TBI. Here, we discuss the inflamed brain after TBI and radiation injury. We further review the status of stem cells in the inflamed brain and the applications of cell therapy in sequestering inflammation in TBI.

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The impact of deep space radiation on cognitive performance: From biological sex to biomarkers to countermeasures

Cited by 31 publications

References 42 publications

Mouse Genomic Associations withEx VivoSensitivity to Simulated Space Radiation

Mouse Genomic Associations withEx VivoSensitivity to Simulated Space Radiation

Astrocytes regulate vascular endothelial responses to simulated deep space radiation in a human organ-on-a-chip model

Stem Cell Therapy for Sequestration of Traumatic Brain Injury-Induced Inflammation

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