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Project Title:  VNSCOR: Oxidative Stress and the Neuroconsequences of Spaceflight Environment -- Immune Dysregulation and Antioxidant Dietary Countermeasure Efficacy 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 report in PDF pdf
Principal Investigator/Affiliation:   Ronca, April Elizabeth Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch, NASA Human Research Program (HRP)/Human Health Countermeasures (HHC) 
MS 236-7 
Moffett Field , CA 94035 
Email: april.e.ronca-1@nasa.gov 
Phone: 650.604.3595  
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 
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 Behavioral Conditions and Psychiatric Disorders
(2) CNS:Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure (IRP Rev G)
(3) Sensorimotor:Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks (Revised as of IRP Rev M)
Human Research Program Gaps: (1) BMed-102:Given exposures to spaceflight hazards (space radiation, isolation), how do we identify individual susceptibility, monitor molecular/biomarkers and acceptable thresholds, and validate behavioral health and CNS/neurological/neuropsychological performance measures and domains of relevance to exploration class missions? (IRP Rev L)
(2) BMed-103:What are the validated, efficacious treatments (individual or Team-based) and/or countermeasures to prevent adverse behavioral conditions, CNS/neurological, and/or psychiatric disorders caused by either single and/or integrated exposures to spaceflight hazards during exploration class missions? (IRP Rev L)
(3) BMed-104:Given the potentially negative spaceflight associated CNS changes and behavioral experiences of stressors during long-duration missions (e.g., isolation, confinement, reduced sensory stimulation, altered gravity, space radiation), what are validated modifications to habitat/vehicle to mitigate stressors impacting on CNS / cognition / behavioral health? (IRP Rev L)
(4) BMed-105:Given the potentially negative spaceflight associated CNS/cognitive changes and behavioral experiences of stressors during long-duration missions (e.g., isolation, confinement, reduced sensory stimulation, altered gravity, space radiation), what are validated medical or dietary countermeasures to mitigate stressors impacting on CNS / cognition / behavioral health? (IRP Rev L)
(5) BMed-107:What are the long-term changes and risks to astronaut health post-mission that, when using a continuity of care model, helps retrospectively identify and understand individual susceptibility (e.g., hereditary, dose, thresholds) to mitigate adverse CNS, cognitive, and behavioral health changes resulting from long-duration exploration missions, promoting the behavioral health of current and future crews? (IRP Rev L)
(6) BMed-108:Given each crewmember will experience multiple spaceflight hazards simultaneously, we need to identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., space radiation, altered gravity, isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes (IRP Rev L)
(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) (IRP Rev M)
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 and gender 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 Type: Description: (Last Updated: 05/24/2022) 

Show Cumulative Bibliography Listing
 
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

Project Title:  VNSCOR: Oxidative Stress and the Neuroconsequences of Spaceflight Environment -- Immune Dysregulation and Antioxidant Dietary Countermeasure Efficacy 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 report in PDF pdf
Principal Investigator/Affiliation:   Ronca, April Elizabeth Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch, NASA Human Research Program (HRP)/Human Health Countermeasures (HHC) 
MS 236-7 
Moffett Field , CA 94035 
Email: april.e.ronca-1@nasa.gov 
Phone: 650.604.3595  
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 
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 Behavioral Conditions and Psychiatric Disorders
(2) CNS:Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure (IRP Rev G)
(3) Sensorimotor:Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks (Revised as of IRP Rev M)
Human Research Program Gaps: (1) BMed-102:Given exposures to spaceflight hazards (space radiation, isolation), how do we identify individual susceptibility, monitor molecular/biomarkers and acceptable thresholds, and validate behavioral health and CNS/neurological/neuropsychological performance measures and domains of relevance to exploration class missions? (IRP Rev L)
(2) BMed-103:What are the validated, efficacious treatments (individual or Team-based) and/or countermeasures to prevent adverse behavioral conditions, CNS/neurological, and/or psychiatric disorders caused by either single and/or integrated exposures to spaceflight hazards during exploration class missions? (IRP Rev L)
(3) BMed-104:Given the potentially negative spaceflight associated CNS changes and behavioral experiences of stressors during long-duration missions (e.g., isolation, confinement, reduced sensory stimulation, altered gravity, space radiation), what are validated modifications to habitat/vehicle to mitigate stressors impacting on CNS / cognition / behavioral health? (IRP Rev L)
(4) BMed-105:Given the potentially negative spaceflight associated CNS/cognitive changes and behavioral experiences of stressors during long-duration missions (e.g., isolation, confinement, reduced sensory stimulation, altered gravity, space radiation), what are validated medical or dietary countermeasures to mitigate stressors impacting on CNS / cognition / behavioral health? (IRP Rev L)
(5) BMed-107:What are the long-term changes and risks to astronaut health post-mission that, when using a continuity of care model, helps retrospectively identify and understand individual susceptibility (e.g., hereditary, dose, thresholds) to mitigate adverse CNS, cognitive, and behavioral health changes resulting from long-duration exploration missions, promoting the behavioral health of current and future crews? (IRP Rev L)
(6) BMed-108:Given each crewmember will experience multiple spaceflight hazards simultaneously, we need to identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., space radiation, altered gravity, isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes (IRP Rev L)
(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) (IRP Rev M)
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 and gender 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 Type: Description: (Last Updated: 05/24/2022) 

Show Cumulative Bibliography Listing
 
 None in FY 2020