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Project Title:  VNSCOR: Mechanisms of Radiation-Induced Changes in Sustained Attention and Social Processing (80NSSC22K0022) Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
Start Date: 12/14/2021  
End Date: 12/13/2023  
Task Last Updated: 01/26/2022 
Download report in PDF pdf
Principal Investigator/Affiliation:   Davis, Catherine M. Ph.D. / Henry M. Jackson Foundation 
Address:  6720-A Rockledge Dr. 
 
Bethesda , MD 20817-1891 
Email: catherine.davis-takacs@usuhs.edu 
Phone: 301-295-5826  
Congressional District:
Web:  
Organization Type: NON-PROFIT 
Organization Name: Henry M. Jackson Foundation 
Joint Agency:  
Comments: Campus address (Jan 2022): Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814. NOTE: PI formerly at Johns Hopkins University; moved to Henry M. Jackson Foundation for the Advancement of Military Medicine in fall 2020.  
Co-Investigator(s)
Affiliation: 
Hienz, Robert  Ph.D. Johns Hopkins University 
Robinson, Siobhan  Ph.D. Hamilton College 
Project Information: Grant/Contract No. 80NSSC22K0022 
Responsible Center: NASA JSC 
Grant Monitor: Whitmire, Alexandra  
Center Contact:  
alexandra.m.whitmire@nasa.gov 
Solicitation / Funding Source: 2016-2017 HERO NNJ16ZSA001N-SRHHC. Appendix E: Space Radiobiology and Human Health Countermeasures Topics 
Grant/Contract No.: 80NSSC22K0022 
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) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) HFBP Bmed:Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders (IRP Rev J)
(2) Sensorimotor:Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks (Revised as of IRP Rev M)
Human Research Program Gaps: (1) BMed-101:We need to identify, quantify, and validate the key selection factors for astronaut cognitive and behavioral strengths (e.g., resiliency) and operationally-relevant performance threats for increasingly Earth independent, long-duration, autonomous, and/or long-distance exploration missions (IRP Rev L)
(2) 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)
(3) 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)
(4) 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)
(5) 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)
(6) 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: [Ed. note Jan 2022: Continuation with same Principal Investigator (PI) Dr. Catherine Davis, of "VNSCOR: Mechanisms of Radiation-Induced Changes in Sustained Attention and Social Processing," grant 80NSSC18K108 when PI was at Johns Hopkins University. See also project, "VNSCOR: Responses of the Nervous System to Chronic, Low Dose Charged Particle Irradiation" (Principal Investigator (PI): Greg Nelson)]

NELSON/DAVIS VIRTUAL NASA Specialized Center of Research (NSCOR): The project is organized as 5 large experimental campaigns to quantify responses for an interrelated set of central nervous system (CNS) outcome measures in mice to acute and protracted exposures to protons at a dose of 0.5 Gy and sham controls; acute and protracted exposures to 0.25 and 0.5 Gy of charged particles; and acute and protracted exposures to 0.5 and 1.5 Gy of gamma rays. This research builds on previous studies that demonstrated that proton and HZE (high charge energy) exposures result in individual differences in deficits in sustained attention, but more general deficits in recognition memory. This current project is combined with "Responses to the Nervous System to Chronic, Low Dosed Charged Particle Irradiation" (PI: Nelson) in order to explore if these effects are LET (linear energy transfer)-dependent for 16O ions, add a relatively understudied, but important, ion (4He), and examine CNS effects in whole animals following fractionated exposures, and the interaction of other space flight factors (e.g., sleep fragmentation).

Revised Specific Aims:

Aim 1a: Effects of protracted exposure to five-ion GCR [galactic cosmic rays] sim (1H, 4He, 28Si, 16O, 56Fe)

Aim 1b: Effects of protracted exposure to GCR sim without protons (4He, 28Si, 16O, 56Fe)

Aim 1c: Effects of protracted exposure to protons only

Aim 1d: Acute exposure to 4He (250 MeV/n)

Aim 2a: Neuronal activation and molecular markers following radiation

Aim 2b: Chemogenetic silencing of mPFC subregions

Specific Aims:

1) Determine the effects of acute, single 16O and 4He ion exposures on sustained attention, social odor recognition memory, and social dominance. (This aim has been modified in order to integrate with Nelson project);

2) Determine the effects of a fractionated exposure on sustained attention and recognition memory in comparison to the effects of single ion exposures on these measures;

3) Determine the effects of circadian disruptions and sleep fragmentation on sustained attention and recognition memory following radiation exposure (This aim has been modified in order to integrate with Nelson project);

4) Examine the underlying mechanisms of these deficits using immunohistochemical and pharmacogenetic procedures.

ORIGINAL PROPOSAL DESCRIPTION: Assessing the biological consequences of living in the space radiation environment represents one of the highest priority areas of NASA research. Of critical importance is the need for an assessment of the vulnerabilities of the central nervous system (CNS) leading to functional neurobehavioral changes during long-term space missions, and the development of effective countermeasures to such risks. The present proposal addresses this need via the application of an animal model to 1) determine the effects of acute, single 16O and 4He ion exposures on sustained attention, social odor recognition memory, and social dominance; 2) determine the effects of a fractionated exposure on sustained attention and recognition memory in comparison to the effects of single ion exposures on these measures; 3) determine the effects of circadian disruptions and sleep fragmentation on sustained attention and recognition memory following radiation exposure; and 4) examine the underlying mechanisms of these deficits using immunohistochemical and pharmacogenetic procedures.

Prior research has 1) identified rats that are sensitive to radiation-induced deficits in sustained attention and 2) shown that acute, single ion exposures alter social motivation and social odor recognition memory. The current proposal will determine how the immediate effects of irradiation impact subsequent neurobehavioral deficits by assessing various behavioral, physiological, and neurobiological markers of radiation exposure at early and later time points post-exposure. Groups of animals will be trained on a rodent version of the human psychomotor vigilance test, exposed to radiation, and then tested for both social processing and sustained attention deficits following exposure; subsets of rats will be implanted with biotelemetry devices to measure fluctuations in spontaneous locomotor activity and body temperatures following radiation exposure and changes in sleep or circadian disruptions. Individual variations in these behavioral, physiological, or neurobiological responses following radiation will be assessed. Likely mechanisms of damage to the CNS following radiation exposure will be examined using brain tissue, in addition to a pharmacogenetic technique to determine the severity of radiation-induced neurobehavioral deficits.

Research Impact/Earth Benefits: The results of the current project will be used to understand how radiation exposure affects the central nervous system to induce deficits in neurobehavioral function.

Task Progress & Bibliography Information FY2022 
Task Progress: New project for FY2022.

Note this is continuation, with same Principal Investigator (PI) Dr. Catherine Davis, of "VNSCOR: Mechanisms of Radiation-Induced Changes in Sustained Attention and Social Processing," grant 80NSSC18K108 when PI was at Johns Hopkins University. See that project for previous reporting.

Bibliography Type: Description: (Last Updated: 07/01/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2022