Task Variation in CNS damage signaling and blood sentinels of neuropathology after exposure to space radiation.
Last Published:  07/30/21 01:05:34 PM (Central)
Short Title: CBS CNS Damage Signaling Neuropathology (Wyrobek)
Responsible HRP Element: Human Factors and Behavioral Performance
Collaborating Org(s):
Human Factors and Behavioral Performance (HFBP) Element
Human Health Countermeasures (HHC) Element
Space Radiation (SR) Element
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):
NIPR
Aims:

Aim 1. Characterize the persistence of radiation-induced molecular abnormalities in cortex and hippocampus after low-dose exposures to 56Fe particles, and compare the predictions for CNS tissue damage and late-onset neuropathologies in similarly irradiated mice and rats.

Aim 1a.
Use archived CNS tissue from SD rats collected at 4 and 9 months after low-dose exposures, and generate new transcriptomics (3’TAGseq) and new metabolomics profiles (untargeted metabolism and targeted complex lipids) from cortex and hippocampus. These data will be integrated with prior proteomics profiles from hippocampus at 9 months after exposure to build a predictive model of CNS tissue damage and risks for neuropathology, with emphasis on vascular and immune abnormalities.

Aim 1b.
Compare molecular responses in cortex and hippocampus of mice and rats at 9 months after exposure to evaluate cross- species consistency. The predictive model will be built using integrating bioinformatics and biostatistical approaches.

Aim 2
. Identify persistent bio-effect markers in peripheral blood and CSF that correlate with molecular damage in CNS vascular or immune functions.

Aim 2a.
will investigate the metabolomics profiles of archived CSF and archived peripheral blood plasma for the same animals. 

Aim 2b.
will determine whether the blood metabolites associated with CNS tissue damage correlate with individual variation in radiation-susceptibility for anxiety as measured in the elevated plus maze.
Resources (None Listed)
Mappings
RiskRisk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
GapBMed-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.
GapBMed-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?
GapBMed-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?
GapBMed-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?
GapBMed-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.
You are here!TaskVariation in CNS damage signaling and blood sentinels of neuropathology after exposure to space radiation.

RiskRisk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes
You are here!TaskVariation in CNS damage signaling and blood sentinels of neuropathology after exposure to space radiation.