Gap CBS-CNS - 2: Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?
Last Published:  07/31/19 10:05:30 AM (Central)
Responsible Element: Space Radiation (SR)
Status: Open
Description

Initial State of Gap:

Possible late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are a documented concern for human exploration of space. Late CNS risks include neurological disorders such as Alzheimer’s disease, dementia or accelerated aging as well as psychological issues including depression and anxiety. However, given the lack of human epidemiology data on which to estimate this risk, projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of this risk and to establish validity of the current PEL. Near-term experimental research is focused on 2 to 4 particle types. This will have to be broadened to 6 to 8 types and GCR mixed-fields to be useful for astronaut risk projections.

    

Approach:

     Ground-based, peer-reviewed research using cell and animal models to acquire necessary knowledge for accurate risk quantification and uncertainty reduction for late CNS adverse changes due to space radiation exposure. Where feasible, identify biomarkers of disease prognosis/progression and outcome pathways for use in monitoring adverse late CNS outcomes and for use in BCM selection as required.

 Interim Steps:

  • Define long term risks of concern: Neurodegenerative disorders and neuropsychological issues such as depression and anxiety
  • Identify appropriate models and endpoints for assessment of late radiation effects on the CNS
  • Clarify the relationship of short term effects to long term effects
  • Identify adverse outcome pathways and underlying mechanisms of change
  • Broaden initial experiment to a larger number of GCR particle types and energies including mixed fields representative of GCR and different shielding configurations including the Martian surface
  • Broaden initial experiments to investigate effects of dose protraction or fractionation
  • Develop methods for relating animal endpoints to human endpoints including feasibility of identifying key biomarkers/indexed metrics with pathological correlations (disease-linked biomarkers)
Target for Closure
  • Quantify the dose responses and validate the existence of dose thresholds for late adverse CNS effects from space radiation.
  • Organize CNS reactions to radiation exposure into adverse outcome pathway(s) related to known diseases and biomarkers.
  • Determine the post-mission significance of adverse changes elicited by mission-relevant exposure.
Mappings
Risk Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
Risk Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
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Documentation:
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