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EXPERIMENT INFORMATION

Molecular Characterization of Long-Term Degenerative CNS Risks from Space Radiation (NNA11AA58I)
Principal Investigator
Research Area:
Radiation biology
Species Studied
Scientific Name: Rattus norvegicus Species: Rats

Description
OBJECTIVES:
The objectives of this research were to characterize the persistent defects in neuro-signaling and cellular damage to central nervous system (CNS) tissue after cranial exposure to space radiation and to identify the critical molecular changes associated with individual variation in persistent neurocognitive deficits, using the rat model. The investigators reported global changes in transcript expression profiles in the hippocampus and choroid plexus (CP) tissues of old animals that were exposed to 56Fe or 12C beams in their youth. They identified changes in the predicted protein expression in the CP that correlated with the magnitude of persistent neurocognitive deficit (i.e., to ~22 months of age). They conducted comparative analyses of radiation-induced changes in CP signaling and cellular architecture that are associated with neurocognitive deficits, using CNS tissue collected from animals exposed at various doses of 56Fe or 12C after they were tested for neurocognitive deficits. Furthermore, they also investigated the early onset of radiation-induced changes to hippocampal and CP signaling, CP architecture, hippocampal neurogenesis, and composition of the cerebrospinal fluid (CSF) at ~3 months after exposure to both high and low-fluence 56Fe, and examined the association between molecular defects and neurocognitive changes within each irradiated animal.

This study had the following specific aims:

  1. Characterize the dose dependence of persistent signaling and cellular defects in the CP and hippocampal zones of neurogenesis of 12C- and 56Fe-exposed rats that have persistent deficits in their cognitive function and motor behavior.
  2. Characterize the time course of cellular and signaling defects in the CP of rats irradiated with 56Fe beams and determine the temporal relationship between CP defects and abnormal hippocampal neurogenesis.
  3. Determine whether irradiated animals with defective CP also produce CSF deficient in critical metabolites or proteins that are critical for adult neurogenesis, using proteomic and metabolomic approaches.


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Publications
Lowe XL and Wyrobek AJ. Characterization of the early CNS stress biomarkers and profiles associated with neuropsychiatric diseases. Current Genomics. 2012. September; 13(6):489-97. [DOI]

Keywords
Radiation effects
HZE particles
Hippocampus
Central nervous system

Data Information
Data Availability
Archive is complete. Data sets are not publicly available but can be requested.
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Parameters
Cerebral spinal fluid
Hippocampus abnormalities
Radiation exposure
Radiation exposure, central nervous system (CNS)

Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
Ground 05/01/2009 In Progress

Human Research Program (HRP) Human Research Roadmap (HRR) Information
Crew health and performance is critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) investigates and mitigates the highest risks to human health and performance, providing essential countermeasures and technologies for human space exploration. Risks include physiological and performance effects from hazards such as radiation, altered gravity, and hostile environments, as well as unique challenges in medical support, human factors, and behavioral health support. The HRP utilizes an Integrated Research Plan (IRP) to identify the approach and research activities planned to address these risks, which are assigned to specific Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.

The Human Research Roadmap is located at: https://humanresearchroadmap.nasa.gov/

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Additional Information
Managing NASA Center
Johnson Space Center (JSC)
Responsible NASA Representative
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Date
01/01/2011
Proposal Source
2010 Space Radiobiology NNJ10ZSA001N