Short Title:
CBS VNSCOR #1 - Radiation Dose Rate Effectiveness Factors (Nelson)
Responsible HRP Element:
Human Factors and Behavioral Performance
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Collaborating Org(s):
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| Human Health Countermeasures (HHC) Element |
| Other: |
| Space Radiation (SR) Element |
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Funding Status:
Active - Currently funded and in progress
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Procurement Mechanism(s):
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Aims:
Nelson/Davis Virtual NSCOR: The project is an experimental campaign combined with "Mechanisms of Radiation-Induced Neurobehavioral Defictis" (PI: Davis)(see above) 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. All proposed work will use wild type mice and will be performed under IACUC approved protocols in AAALAC-certified facilities at Loma Linda University (LLU), the University of California, Irvine (UCSF) and Brookhaven National Laboratory (BNL). For all three specific aims the species is Mus musculus, strain C57Bl/6J. Ages are 5 - 6 months at acquisition and the beginning of 42 day irradiation procedures. Sexes are males and females. Scheduled euthanasia's are at 1 week, 30 days, 90 days, 6 months and 12 months post-irradiation. Behavioral testing will occur prior to the use of the same animals for terminal assays. All outcome measures will be quantified in males (N=960) and a subset of measures less prone to sex-dependent variability will be quantified in females (N=220) for a total of N = 1180.
Aim 1: Quantify responses for an interrelated set of CNS outcome measures in mice to acute and protracted exposures to protons at a dose of 0.5 Gy and sham controls. Derive DREFs for the set of outcome measures.
Aim 2: Quantify responses for an interrelated set of CNS outcome measures in mice to acute and protracted exposures to simulated galactic cosmic ray (GCRsim) radiation at doses of 0.25 and 0.5 Gy. Derive DREFs for the set of outcome measures.
Aim 3: Quantify responses for an interrelated set of CNS outcome measures in mice to protracted exposures to 137Cs gamma radiation at doses of 0.75 and 2.0 Gy. Combine results with those of specific aim 2 to determine RBEs for the set of outcome measures for protracted GCRsim exposure.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
-Goal of the proposed project is to determine dose rate effectiveness factors (DREFs) and relative biological effectiveness factors (RBEs) for an interrelated set of central nervous system (CNS) outcome measures in mice following protracted exposures to protons and a simulated galactic cosmic ray spectrum of charged particles (GCRsim). These factors are required to extrapolate dose-response measurements based on acute laboratory exposures to the protracted exposure condition of space flight. The outcome measures include: 1) behavior in four neuropsychological domains – cognition, affect, social interactions, and sensorimotor, 2)neuron activity pattern imaging parameters for synaptic excitability and plasticity, 3) synaptic number and composition, 4) markers of oxidative stress; neuroinflammation, and synapse composition. Because the different outcome measures are dependent on different (but interrelated) processes and tissue components, a family of DREFs and RBEs will be derived.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None