Menu

 

The NASA Task Book
Advanced Search     
Back to Search Results    

Project Title:  VNSCOR: Oxidative Stress and the Neuroconsequences of Spaceflight Environment Reduce
Images: icon  Fiscal Year: FY 2023 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
 Start Date: 10/01/2019  
End Date: 09/30/2025  
Task Last Updated: 08/03/2023 		 Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Ronca, April Elizabeth Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch 
MS 261 
Moffett Field , CA 94035 		 Email: april.e.ronca-1@nasa.gov 
Phone: 650.400.6019  
Congressional District: 18 
Web:  
 Organization Type: NASA CENTER 
Organization Name: NASA Ames Research Center 
Joint Agency:  
Comments: November 2019: PI is located at NASA Ames Research Center and remains affiliated with Wake Forest University School of Medicine 
Co-Investigator(s)
Affiliation: 
Tahimic, Candice  Ph.D. University of North Florida 
Paul, Amber  Ph.D. Embry-Riddle Aeronautical University 
Mhatre, Siddhita  Ph.D. NASA Ames Research Center 
Iyer, Janani  Ph.D. NASA Ames Research Center 
Alwood, Joshua  NASA Ames Research Center 
Puukila, Stephanie  Ph.D. Blue Marble Space Institute of Science 
Key Personnel Changes / Previous PI: NOTE: Dr. April Ronca has retired. This project continues under a new Principal Investigator, Dr. Joshua Alwood. For subsequent reporting, see "VNSCOR: Oxidative Stress and the Neuroconsequences of Spaceflight Environment" under PI Alwood (Ed., 11/24/24). Stephanie Puukila, PhD added as Ames Co-I with expertise in space radiation, animal cognition and behavior, and countermeasures.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Whitmire, Alexandra  
Center Contact:  
alexandra.m.whitmire@nasa.gov 
Unique ID: 12618  		Solicitation / Funding Source: 2018 HERO 80JSC018N0001-Crew Health and Performance (FLAGSHIP, OMNIBUS). Appendix A-Flagship, Appendix B-Omnibus 
Grant/Contract No.: Internal Project 
Project Type: Ground 
Flight Program:  
TechPort: No  		No. of Post Docs: 2 
No. of PhD Candidates:  
No. of Master's Candidates: 2 
No. of Bachelor's Candidates: 8  		No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees: 2 
Human Research Program Elements: (1) HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Human Research Program Risks: (1) BMed:Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
(2) Sensorimotor:Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks
Human Research Program Gaps: (1) BMed-102:Identify and characterize key C/P/Psy/N outcome measures (biomarkers) and domains of relevance that are at risk due to spaceflight environmental stressors in exploration class missions and determine validated thresholds for identified biomarkers of adverse C/P/Psy/N outcomes to enable mission objectives and identify indicators of risk before progression to clinical levels of impairment.
(2) BMed-103:Identify validated, evidence-based countermeasures to prevent or treat adverse C/P/Psy/N conditions caused by single or combined exposures to spaceflight environmental stressors.
(3) BMed-104:Identify design features and requirements of the habitat/vehicle and mission architecture to mitigate stressors impacting C/P/Psy/N health.
(4) BMed-105:Identify validated medical or dietary countermeasures to mitigate spaceflight environmental stressors impacting C/P/Psy/N health.
(5) BMed-107:Determine long-term changes and risks to astronaut health post-mission that retrospectively predicts individual susceptibility to adverse C/P/Psy/N outcomes and informs countermeasure implementation in current and future crews.
(6) BMed-108:Identify and characterize the potential impacts of combined spaceflight environmental stressors to inform both validated threshold limits and countermeasure for adverse C/P/Psy/N outcomes.
(7) SM-104:Evaluate how weightlessness-induced changes in sensorimotor/vestibular function relate to and/or interact with changes in other brain functions (sleep, cognition, attention).
Flight Assignment/Project Notes: NOTE: End date changed to 09/30/2025 per L. Juliette/JSC (Ed., 5/7/22)

Task Description: The proposed project will test the hypothesis that Ionizing Radiation (IR), microgravity, and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. Specific Aims for this project are: (1) Determine dose-response curves for acute ‘Five-Ion GCR (galactic cosmic ray) Simulation’ exposure for immune, brain, and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain, and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. The project relies on established and highly translatable ground-based mouse models and assays with IR exposures to be performed at the NASA Space Radiation Laboratory (NSRL). The experimental approach will provide definitive data on the timing and mechanisms involved in the oxidative stress response, immune, and brain changes, and ensuing functional (behavioral/cognitive) impairments expected during human transit to Mars. This project will identify potential immune biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. This proposal addresses NASA’s efforts to rapidly advance the characterization of risks and identifying appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Further, despite historically low numbers of females astronauts, recent NASA Astronaut Corps class selections, comprised of 50% and 40% women as compared to men, signal the need to understand how sex differences affect physiological adaptation and health in the space environment. This integrative project, developed by a cross-disciplinary team highly experienced in spaceflight and radiation research, utilizes established space biosciences research protocols and variables, and time-honored, as well as modern, research methodologies. We will address major risks and associated gaps: (1) Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation (CNS), (2) Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks (SM), and Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders that have been combined into the NASA CNS, BMed, and SM (CBS) Integrated Research Plan. Here we have adhered to primary goals set forth in Human Exploration Research Opportunities (HERO) Appendix A to determine how key features of the deep space environment may interact to increase risk to a crew by negatively impacting health and performance, and we have identifed and developed strategies to characterize and mitigate the potential risks via countermeasures.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2023 
Task Progress: Extensive progress was made during this reporting period on the first two project aims with two publications and multiple abstracts focussed on acute GCRsim dose-response and combinatorial effects of spaceflight stressors (isolation, simulated microgravity, and simulated galactic cosmic rays/GCRsim) on crew-aged mice. Data were collected on neural, behavioral, and immune outcomes at varying timepoints in relation to spaceflight stressor exposure.

The Virtual NASA Specialized Center of Research (VNSCOR). The VNSCOR Team met extensively to discuss touch points across the project and hone our experimental designs. The VNSCOR includes two species, mouse and rat, with mature male and female subjects approximating crew ages, and six standardization protocols across three laboratories. The timeline for the combined space stress model remains identical across groups with all animals experiencing each stressor for identical lengths of time and at the same timepoints – this will allow a standard model at the NASA Space Radiation Laboratory (NSRL) to be developed for future studies. According to this timeline, all Principal Investigator (PI) teams will perform hindlimb unloading as the microgravity model, and irradiate all animals with the 5-ion GCRsim at both a low (15 cGy) and high dose (50 cGy) that most closely mimics the mission travel time to Mars. A slightly lower protein diet, containing no estradiol, will be used to closely mimic the diet of astronauts and limit the effects of circulating estrogen. Additionally, efforts are being made to create similar animal care and handling conditions. To maintain all original grant aims, each group will return to their respective institutions and perform a minimum of two identical behavioral assays to measure changes in sensorimotor (adhesive removal) and memory (novel object recognition) functions. Using three Luminex-based arrays, each group will evaluate peripheral blood markers to elucidate potential predictive biomarkers of behavioral performance. These data together, will be combined into a predictive statistical model to identify potential biomarkers that may predict behavior decrements and neuroinflammation across three institutions and two species.

Predictive modeling efforts are underway integrating multiple measures derived from the current project with planned expansions across VNSCOR Teams.

Bibliography: Description: (Last Updated: 05/15/2025) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Tahimic CGT, Dubose M, Korostenskij I, Semel M, Mhatre SD, Alwood JS, Yasaman Shirazi-Fard Y, Lowe M, Iyer JS, Puukila SA, Paul AM, Rubinstein L, Delp M, Goukassian D, Ronca AE. "Defining the molecular signatures of cardiovascular responses to simulated space radiation." Committee on Space Research (COSPAR) 2022 44th Scientific Assembly, Athens, Greece, July 16-24, 2022.

Abstracts. Committee on Space Research (COSPAR) 2022 44th Scientific Assembly, Athens, Greece, July 16-24, 2022. , Jul-2022

Abstracts for Journals and Proceedings Puukila SA, Siu O, Mhatre SD, Lowe M, Tabares Ruiz SN, Tahimic CGT, Rubinstein L, Alwood JS, Ronca AE. "Neurobehavioral effects of five-ion GCRsim exposure in male and female mice." 68th Annual Meeting, Radiation Research Society, Waikoloa Village, Hawaii, October 16-19, 2022.

Abstracts. 68th Annual Meeting, Radiation Research Society, Waikoloa Village, Hawaii, October 16-19, 2022. , Oct-2022

Abstracts for Journals and Proceedings Ronca AE, Iyer JS, Mhatre SDS, Puukila SA, Tabares Ruiz SN, Hayes J, Dubose M, Siu O, Burke M, Semel M, Lowe M, Shirazi-Fard Y, Rubinstein L, Sowa MB, Paul AM, Tahimic CGT, Alwood JS. "Sex differences and deep space stressors: effects of 5-ion GCRsim, simulated microgravity and social isolation on immune function, brain and behavior in mice." 68th Annual Meeting, Radiation Research Society, Waikoloa Village, Hawaii, October 16-19, 2022.

Abstracts. 68th Annual Meeting, Radiation Research Society, Waikoloa Village, Hawaii, October 16-19, 2022. , Oct-2022

Abstracts for Journals and Proceedings Mitchell C, Burke M, Christenson LK, Ronca AE, Paul M. "Assessment of dose-dependent endocrine and immune responses to simulated ionizing radiation. " American Astronautical Society, Von Braun Symposium, Huntsville, Alabama, October 26-28, 2022.

Abstracts. American Astronautical Society, Von Braun Symposium, Huntsville, Alabama, October 26-28, 2022. , Oct-2022

Abstracts for Journals and Proceedings Juarez K, Burke M, Larsen E, Wong K, Talyansky Y, Tahimi CGT, DuBose M, Semel M, Christenson LK, Iyer JS, Mhatre SD, Puukila SA, Tabares Ruiz SN, Rubinstein L, Lowe M, Shirazi-Fard Y, Alwood JS, Ronca AE, Paul AM. "Investigating the relationship between immune function and adrenal hormones following simulated ionizing radiation." American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022.

Abstracts. American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022. , Nov-2022

Abstracts for Journals and Proceedings Rubinstein L, Paul AM, Mhatre SD, Iyer JS, Puukila SA, Siu O, Lowe M, Houseman C, Abegaz M, Tabares Ruiz SN, O’Neil N, Allen AR, Alwood JS, Globus RK, Tahimic CGT, Ronca AE. "Neuro-behavioral consequences of low dose radiation social isolation and sex differences in the longevity MCAT mouse model." American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022.

Abstracts. American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022. , Nov-2022

Abstracts for Journals and Proceedings Siu O, Puukila SA, Rubinstein L, Tahimic CGT, Lowe M, Korosteskij I, Semel M, Iyer JS, Mhatre SD, Shirazi-Fard Y, J. S. Alwood JS, Paul AM, Ronca AE. "The effects to exposure of simulated spaceflight radiation on behavioral health of male and female mice. " American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022.

Abstracts. American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022. , Nov-2022

Abstracts for Journals and Proceedings Puukila SA, Siu O, Mhatre SD, Lowe M, Tabares Ruiz SN, Tahimic CGT, Rubinstein L, Alwood JS, Ronca AE. "Early and late neurobehavioral effects of male and female mice exposed to five-ion GCRsim." American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022.

American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022. , Nov-2022

Abstracts for Journals and Proceedings Taylor SC, Nies P, Stoltz A, Olson M, Burke M, Paul, Tahimic C, Ronca A, Christenson L. "Impact of simulated galactic cosmic radiation and hindlimb unloading on the mouse adrenal gland morphology and histology." American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022.

Abstracts. American Society for Gravitational and Space Biology, Houston, Texas, November 9-12, 2022. , Nov-2022

Abstracts for Journals and Proceedings Paul AM, Mitchell C, Burke M, Olson M, Juran C, Christenson LK, Puukila SA, Tabares Ruiz SN, Iyer, JS, Mhatre SD, DuBose, M, Lowe M, Rubinstein L, Sowa M, Shirazi-Fard Y, Alwood JS, Tahimic CGT, Ronca AE. "Integrative endocrine and immune responses to simulated ionizing radiation in mice." 2023 NASA Human Research Program Investigators’ Workshop, Galveston, Texas, February 7-9, 2023.

Abstracts. 2023 NASA Human Research Program Investigators’ Workshop, Galveston, Texas, February 7-9, 2023. , Feb-2023

Abstracts for Journals and Proceedings Tahimic CGT, DuBose Mollie, Semel M, Korostenskij I, Santos J, Krikourian O, Palatsidis I, Puukila SA, Mhatre SD, Iyer JS, Paul A, Alwood JS, Shirazi-Fard Y, Rubinstein L, Tabares Ruiz SN, Lowe M, Delp M, Goukassian D, Ronca AE. "Cardiovascular responses to simulated spaceflight: molecular signatures and surrogate outputs to measure CVD risk." 2023 NASA Human Research Program Investigators’ Workshop, Galveston, Texas, February 7-9, 2023.

Abstracts. 2023 NASA Human Research Program Investigators’ Workshop, Galveston, Texas, February 7-9, 2023. , Feb-2023

Abstracts for Journals and Proceedings Ronca AE, Puukila, SA, Tabares Ruiz SN, Iyer JS, Mhatre SD, Dubose M, Hayes J, Siu O, Burke M, Semel M, Lowe M, Rubinstein L, Sowa M, Shirazi-Fard Y, Alwood JS, Paul AM, Tahimic CGT. "Sex-specific effects of simulated spaceflight on immune, neural and behavioral responses in crew age-matched mice. " 2022 NASA Human Research Program Investigators’ Workshop.

Abstracts. 2022 NASA Human Research Program Investigators’ Workshop. , Nov-2022

Articles in Other Journals or Periodicals Burke M, Wong K, Talyansky Y, Mhatre S, Mitchell C, Juran C, Olsen M, Iyer J, Puukila S, Tahimic C, Christenson, L, Lowe M, Rubinstein L, Shirazi-Fard Y, Sowa M, Alwood JS. Ronca A#, Paul A# (#Corresponding Authors) "Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice." Sci Rep. Accepted 2023 Apr 16. , Apr-2023
Articles in Peer-reviewed Journals Puukila S, Siu O, Rubinstein L, Tahimic CGT, Lowe M, Tabares Ruiz S, Korostenskij I, Semel M, Iyer J, Mhatre SD, Shirazi-Fard Y, Alwood JS, Paul AM, Ronca AE. "Galactic cosmic irradiation alters acute and delayed species-typical behavior in male and female mice." Life (Basel). 2023 May 19;13(5):1214. https://doi.org/10.3390/life13051214 ; PMID: 37240858; PMCID: PMC10223209 , May-2023
Articles in Peer-reviewed Journals Mhatre SD, Iyer J, Puukila S, Paul AM, Tahimic CGT, Rubinstein L, Lowe M, Alwood JS, Sowa MB, Bhattacharya S, Globus RK, Ronca AE. "Neuro-consequences of the spaceflight environment." Neurosci Biobehav Rev. 2022 Jan;132:908-35. https://doi.org/10.1016/j.neubiorev.2021.09.055 ; PubMed PMID: 34767877 , Jan-2022
Back to Search Results    
Project Title:  VNSCOR: Oxidative Stress and the Neuroconsequences of Spaceflight Environment Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
 Start Date: 10/01/2019  
End Date: 09/30/2025  
Task Last Updated: 05/26/2022 		 Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Ronca, April Elizabeth Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch 
MS 261 
Moffett Field , CA 94035 		 Email: april.e.ronca-1@nasa.gov 
Phone: 650.400.6019  
Congressional District: 18 
Web:  
 Organization Type: NASA CENTER 
Organization Name: NASA Ames Research Center 
Joint Agency:  
Comments: November 2019: PI is located at NASA Ames Research Center and remains affiliated with Wake Forest University School of Medicine 
Co-Investigator(s)
Affiliation: 
Tahimic, Candice  Ph.D. University of North Florida 
Paul, Amber  Ph.D. Embry-Riddle Aeronautical University 
Mhatre, Siddhita  Ph.D. NASA Ames Research Center 
Iyer, Janani  Ph.D. NASA Ames Research Center 
Alwood, Joshua  NASA Ames Research Center 
Key Personnel Changes / Previous PI: Joshua Alwood, Ph.D. was added as a CoInvestigator due to his expertise in bone physiology. Linda Guttmann, Ph.D. left the project in December, 2020. Amber Paul, Ph.D. is now at Embry–Riddle Aeronautical University. Candice Tahimic, Ph.D. is now at the University of North Florida.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Whitmire, Alexandra  
Center Contact:  
alexandra.m.whitmire@nasa.gov 
Unique ID: 12618  		Solicitation / Funding Source: 2018 HERO 80JSC018N0001-Crew Health and Performance (FLAGSHIP, OMNIBUS). Appendix A-Flagship, Appendix B-Omnibus 
Grant/Contract No.: Internal Project 
Project Type: Ground 
Flight Program:  
TechPort: No  		No. of Post Docs: 2 
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:   		No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Human Research Program Risks: (1) BMed:Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
(2) Sensorimotor:Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks
Human Research Program Gaps: (1) BMed-102:Identify and characterize key C/P/Psy/N outcome measures (biomarkers) and domains of relevance that are at risk due to spaceflight environmental stressors in exploration class missions and determine validated thresholds for identified biomarkers of adverse C/P/Psy/N outcomes to enable mission objectives and identify indicators of risk before progression to clinical levels of impairment.
(2) BMed-103:Identify validated, evidence-based countermeasures to prevent or treat adverse C/P/Psy/N conditions caused by single or combined exposures to spaceflight environmental stressors.
(3) BMed-104:Identify design features and requirements of the habitat/vehicle and mission architecture to mitigate stressors impacting C/P/Psy/N health.
(4) BMed-105:Identify validated medical or dietary countermeasures to mitigate spaceflight environmental stressors impacting C/P/Psy/N health.
(5) BMed-107:Determine long-term changes and risks to astronaut health post-mission that retrospectively predicts individual susceptibility to adverse C/P/Psy/N outcomes and informs countermeasure implementation in current and future crews.
(6) BMed-108:Identify and characterize the potential impacts of combined spaceflight environmental stressors to inform both validated threshold limits and countermeasure for adverse C/P/Psy/N outcomes.
(7) SM-104:Evaluate how weightlessness-induced changes in sensorimotor/vestibular function relate to and/or interact with changes in other brain functions (sleep, cognition, attention).
Flight Assignment/Project Notes: NOTE: End date changed to 09/30/2025 per L. Juliette/JSC (Ed., 5/7/22)

Task Description: The proposed project will test the hypothesis that Ionizing Radiation (IR), microgravity, and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. Specific Aims for this project are: (1) Determine dose-response curves for acute ‘Five-Ion GCR (galactic cosmic ray) Simulation’ exposure for immune, brain, and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain, and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. The project relies on established and highly translatable ground-based mouse models and assays with IR exposures to be performed at the NASA Space Radiation Laboratory (NSRL). The experimental approach will provide definitive data on the timing and mechanisms involved in the oxidative stress response, immune, and brain changes, and ensuing functional (behavioral/cognitive) impairments expected during human transit to Mars. This project will identify potential immune biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. This proposal addresses NASA’s efforts to rapidly advance the characterization of risks and identifying appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Further, despite historically low numbers of females astronauts, recent NASA Astronaut Corps class selections, comprised of 50% and 40% women as compared to men, signal the need to understand how sex differences affect physiological adaptation and health in the space environment. This integrative project, developed by a cross-disciplinary team highly experienced in spaceflight and radiation research, utilizes established space biosciences research protocols and variables, and time-honored, as well as modern, research methodologies. We will address major risks and associated gaps: (1) Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation (CNS), (2) Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks (SM), and Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders that have been combined into the NASA CNS, BMed, and SM (CBS) Integrated Research Plan. Here we have adhered to primary goals set forth in Human Exploration Research Opportunities (HERO) Appendix A to determine how key features of the deep space environment may interact to increase risk to a crew by negatively impacting health and performance, and we have identifed and developed strategies to characterize and mitigate the potential risks via countermeasures.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2021 
Task Progress: The study is underway. Extensive progress was made during this reporting period on the Virtual NASA Specialized Center of Research (VNSCOR). The VNSCOR Team met extensively to discuss touch points across the project and hone our experimental designs. The VNSCOR includes two species, mouse and rat, with mature male and female subjects approximating crew ages, and six standardization protocols across three laboratories. The timeline for the combined space stress model remains identical across groups with all animals experiencing each stressor for identical lengths of time and at the same timepoints – this will allow a standard model at the NASA Space Radiation Laboratory (NSRL) to be developed for future studies. According to this timeline, all Principal Investigator (PI) teams will perform hindlimb unloading as the microgravity model, and irradiate all animals with the 5-ion GCRsim at both a low (15 cGy) and high dose (50 cGy) that most closely mimics the mission travel time to Mars. A slightly lower protein diet, containing no estradiol, will be used to closely mimic the diet of astronauts and limit the effects of circulating estrogen. Additionally, efforts are being made to create similar animal care and handling conditions. To maintain all original grant aims, each group will return to their respective institutions and perform a minimum of two identical behavioral assays to measure changes in sensorimotor (adhesive removal) and memory (novel object recognition) functions. Using three Luminex based arrays each group will evaluate peripheral blood markers to elucidate potential predictive biomarkers of behavioral performance. These data together, will be combined into a predictive statistical model to identify potential biomarkers that may predict behavior decrements and neuroinflammation across three institutions and two species.

In February 2021, our team customized and shipped 100 hindlimb unloadin (HU) cages to Brookhaven National Laboratory (BNL) for the Rosi team, and worked onsite at University of California San Francisco (UCSF) training the Rosi Team in this procedure. Despite the COVID-19 pandemic, my own Team was able to travel to NSRL during this reporting period, complete 5-ion GCRsim exposure, perform acute behavioral (sensorimotor) and immune measures at 72 post-IR, and dissect the Intermediate group. Delayed group mice were shipped to NASA Ames Resarch Center (ARC) to undergo cognitive and behavioral testing, which will be followed by dissection. After dissection, data analysis will begin.

Bibliography: Description: (Last Updated: 05/15/2025) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Paul AM, Rubinstein L, Mhatre SD Iyer J, Wong K, Lowe M, Abegaz M, O’Neil N, Tahimic C, Alwood JS, Globus RK, Ronca AE. "Altered immune differentials between male and female mice independent of ionizing radiation." 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021.

Abstracts. 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021. , Feb-2021

Abstracts for Journals and Proceedings Puukila S, Lemon JA, Ronca AE, Jones JA, Montesinos CA, Boreham DR. "A multi targeted dietary supplement as a potential countermeasure for prolonged, deep space exploration." 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021.

Abstracts. 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021. , Feb-2021

Abstracts for Journals and Proceedings Ronca AE, Rubinstein L, Paul A, Mhatre SD, Iyer JS, Puukila SA, Lowe M, Sowa M, Globus R, Alwood JS, Tahimic C. "Oxidative stress and the neuroconsequences of spaceflight environment - immune dysregulation and antioxidant dietary countermeasure efficacy." 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021.

Abstracts. 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021. , Feb-2021

Abstracts for Journals and Proceedings Rosi S, Sanford L, Ronca A. "The combined space stress model– social isolation, altered gravity, and GCR- effects on memory, sensorimotor function, and neuroinflammatory response as to predict astronaut performance." 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021.

Abstracts. 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021. , Feb-2021

Abstracts for Journals and Proceedings Rubinstein L, Paul A, Mhatre SD, Iyer JS, Puukila SA, Lowe M, Houseman C, Abegaz M, Tabares Ruiz, O’Neil N, Sowa M, Alwood JS, Globus RK, Tahimic C, Ronca AE. "The combined space stress model – social isolation, altered gravity, and GCR – effects on memory, sensorimotor function, and neuroinflammatory response as to predict astronaut performance. " 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021.

Abstracts. 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021. , Feb-2021

Back to Search Results    
Project Title:  VNSCOR: Oxidative Stress and the Neuroconsequences of Spaceflight Environment Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
 Start Date: 10/01/2019  
End Date: 09/30/2023  
Task Last Updated: 11/15/2019 		 Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Ronca, April Elizabeth Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch 
MS 261 
Moffett Field , CA 94035 		 Email: april.e.ronca-1@nasa.gov 
Phone: 650.400.6019  
Congressional District: 18 
Web:  
 Organization Type: NASA CENTER 
Organization Name: NASA Ames Research Center 
Joint Agency:  
Comments: November 2019: PI is located at NASA Ames Research Center and remains affiliated with Wake Forest University School of Medicine 
Co-Investigator(s)
Affiliation: 
Tahimic, Candice  Ph.D. NASA Ames Research Center 
Paul, Amber  Ph.D. NASA Ames Research Center 
Mhatre, Siddhita  Ph.D. NASA Ames Research Center 
Iyer, Janani  Ph.D. NASA Ames Research Center 
Guttmann, Linda  Ph.D. NASA Ames Research Center 
Globus, Ruth  Ph.D. NASA Ames Research Center 
Bhattacharya, Sharmila  Ph.D. NASA Ames Research Center 
Key Personnel Changes / Previous PI: Update as per PI: Ruth Globus, Ph.D. and Sharmila Bhattacharya, Ph.D. left the project before the investigation began (Ed., 5/26/22).
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Williams, Thomas  
Center Contact: 281-483-8773 
thomas.j.will1@nasa.gov 
Unique ID: 12618  		Solicitation / Funding Source: 2018 HERO 80JSC018N0001-Crew Health and Performance (FLAGSHIP, OMNIBUS). Appendix A-Flagship, Appendix B-Omnibus 
Grant/Contract No.: Internal Project 
Project Type: Ground 
Flight Program:  
TechPort: No  		No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:   		No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Human Research Program Risks: (1) BMed:Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
(2) Sensorimotor:Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks
Human Research Program Gaps: (1) BMed-102:Identify and characterize key C/P/Psy/N outcome measures (biomarkers) and domains of relevance that are at risk due to spaceflight environmental stressors in exploration class missions and determine validated thresholds for identified biomarkers of adverse C/P/Psy/N outcomes to enable mission objectives and identify indicators of risk before progression to clinical levels of impairment.
(2) BMed-103:Identify validated, evidence-based countermeasures to prevent or treat adverse C/P/Psy/N conditions caused by single or combined exposures to spaceflight environmental stressors.
(3) BMed-104:Identify design features and requirements of the habitat/vehicle and mission architecture to mitigate stressors impacting C/P/Psy/N health.
(4) BMed-105:Identify validated medical or dietary countermeasures to mitigate spaceflight environmental stressors impacting C/P/Psy/N health.
(5) BMed-107:Determine long-term changes and risks to astronaut health post-mission that retrospectively predicts individual susceptibility to adverse C/P/Psy/N outcomes and informs countermeasure implementation in current and future crews.
(6) BMed-108:Identify and characterize the potential impacts of combined spaceflight environmental stressors to inform both validated threshold limits and countermeasure for adverse C/P/Psy/N outcomes.
(7) SM-104:Evaluate how weightlessness-induced changes in sensorimotor/vestibular function relate to and/or interact with changes in other brain functions (sleep, cognition, attention).
Task Description: The proposed project will test the hypothesis that Ionizing Radiation (IR), microgravity, and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. Specific Aims for this project are: (1) Determine dose-response curves for acute ‘Five-Ion GCR (galactic cosmic ray) Simulation’ exposure for immune, brain, and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain, and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. The project relies on established and highly translatable ground-based mouse models and assays with IR exposures to be performed at the NASA Space Radiation Laboratory (NSRL). The experimental approach will provide definitive data on the timing and mechanisms involved in the oxidative stress response, immune, and brain changes, and ensuing functional (behavioral/cognitive) impairments expected during human transit to Mars. This project will identify potential immune biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. This proposal addresses NASA’s efforts to rapidly advance the characterization of risks and identifying appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Further, despite historically low numbers of females astronauts, the two most recent NASA Astronaut Corps class selections, comprised of 50% and 40% women as compared to men, signal the need to understand how sex differences affect physiological adaptation and health in the space environment. This integrative project, developed by a cross-disciplinary team highly experienced in spaceflight and radiation research, utilizes established space biosciences research protocols and variables, and time-honored, as well as modern, research methodologies. We will address major risks and associated gaps: (1) Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation (CNS), (2) Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight (SM), and Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders that have been combined into the NASA CNS, BMed, and SM Integrated Research Plan. Here we have adhered to primary goals set forth in Human Exploration Research Opportunities (HERO) Appendix A to determine how key features of the deep space environment may interact to increase risk to a crew by negatively impacting health and performance, and identify and develop strategies to characterize and mitigate the potential risks via countermeasures.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2020 
Task Progress: New project for FY2020.

Bibliography: Description: (Last Updated: 05/15/2025) 

Show Cumulative Bibliography
 
 None in FY 2020
Back to Search Results