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EXPERIMENT INFORMATION

Role of Oxidative Stress in Mediating the Effects of Combined Exposure to Simulated Microgravity and Radiation on Neurovascular Remodeling in Mouse (NNX13AL97G)
Principal Investigator
Research Area:
Developmental biology
Species Studied
Scientific Name: Mus musculus Species: Mouse

Description
OBJECTIVES:
One of the main concerns for long-term deep manned space missions are health risk associated with altered gravitational environment and prolonged exposure to low-dose radiation above levels normally found on Earth. Microgravity and radiation exposure has known to produce a number of neurological disturbances and neurodegeneration by space flight condition. However, the pathophysiological process from adaptive response to irreversible oxidative damage in the brain vasculature and the underlying mechanism(s) of these disturbances are less studied and remain unclear. Our proposal seeks to fill in gap by testing the hypothesis that NADPH oxidase is a critical source of the neurovascular oxidative stress following space flight condition that mediates vascular remodeling in the brain, thus disrupting communication between endothelial cells and astrocytes and altering production of extracellular matrix (ECM) proteins. It is further proposed that these changes will contribute to increased vascular permeability and blood-brain barrier (BBB) disturbance, thus resulting in neurological deficit. Together, our unique, integrative, and quantitative activities with advanced imaging techniques, stereological analysis, and behavioral tests will provide insight into the molecular mechanisms of space flight condition-induced oxidative damage on brain tissue and vascular remodeling. Understanding how factors and environmental stress impact on vasculature, tissue remodeling, and function will increase our knowledge and focus toward more effective countermeasures during human space flight and planetary exploration. Our study will also lend new insights into the causes and possible treatments of debilitating neurovascular-related disease and neurodegeneration by targeting NADPH oxidase activation.
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Publications
Mao XW, Nishiyama NC, Pecaut MJ, Campbell-Beachler M, Gifford P, Haynes KE, Becronis C, Gridley DS. Simulated microgravity and low-dose/low-dose-rate radiation induces oxidative damage in the mouse brain. Radiat Res. 2016 Jun;185(6):647-57. pubmed.gov [DOI]

Chang J, Luo Y, Wang Y, Pathak R, Sridharan V, Jones T, Mao XW, Nelson G, Boerma M, Hauer-Jensen M, Zhou D, Shao L. Low doses of oxygen ion irradiation cause acute damage to hematopoietic cells in mice. PLoS One. 2016 Jul 1;11(7):e0158097. pubmed.gov

Seawright JW, Samman Y, Sridharan V, Mao XW, Cao M, Singh P Melnyk S, Koturbash I, Nelson GA, Hauer-Jensen M, Boerma M. Effects of low-dose rate gamma-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart. PLoS One. 2017 Jul 5;12(7):e0180594. pubmed.gov [DOI]

Mao XW, Nishiyama NC, Campbell-Beachler M, Gifford P, Haynes KE, Gridley DS, Pecaut MJ. Role of NADPH oxidase as a mediator of oxidative damage in low-dose irradiated and hindlimb-unloaded mice Radiat Res. 2017 Aug 1. pubmed.gov [DOI]

Data Information
Data Availability
Archiving in progress. Data is not yet available for this experiment.

Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
Ground 05/01/2009 In Progress

Additional Information
Managing NASA Center
Ames Research Center (ARC)
Responsible NASA Representative
Ames Research Center LSDA Level 3
Project Manager: Helen Stewart
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Date
2012
Proposal Source
2012 Space Biology NNH12Z