Short Title:
SR Synaptic Functions- Supplement for CBS Sex Differences (Rosi)
Responsible HRP Element:
Human Factors and Behavioral Performance
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Collaborating Org(s):
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| Human Health Countermeasures (HHC) Element |
| 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:
The Original SR Synaptic Function Task was completed by SR in 2019, and supplemented by CBS for the supplemental aims listed below.
The purpose of this application is to determine how space-relevant doses of radiation affect dendritic maintenance as it pertains to synaptic functions and memory. We hypothesize that space radiation, even at low doses, impairs synaptic functions with negative consequences for cognition and that these effects are mediated by oxidative stress and inflammation. We will use novel mouse models with neuronal-specific overexpression of an antioxidant enzyme to address the role of oxidative stress. The mice will be exposed to space-relevant doses of proton, 56Fe, or 16O and analyzed for acute and late effects. Experimental endpoints will include cognitive functions, dendritic structures and synaptic functions, molecules that control the dendritic system, inflammatory responses, and indices of oxidative stress. This systematic approach will allow us: 1) to connect the functional output of cognition to the molecular pathway that controls synaptic plasticity and memory; and 2) to determine the role of oxidative stress and inflammation in space radiation-mediated changes.
CBS Supplement Specific Aim 1: Study why female mice appear to be more protected than males from GCR. This will be accomplished by examining male/female differences in synaptic composition and microglia activation, the genetic signature of microglia after GCR exposure, sex differences in the genetic signature for the repopulated microglia population.
CBS Supplement Specific Aim 2: Study the possibility of a differential effect of NMDA receptor changes between males and females.
CBS Supplement Specific Aim 3: Map molecular changes to plausible brain performance areas with demonstrated connection between changes in molecular pathways for brain structure changes – predictive of performance decrements.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Final Report on how space-relevant doses of radiation affect dendritic maintenance as it pertains to synaptic functions and memory
Internal Customers:
None
External Customers:
None
Category:
Study Results
Subcategory:
Customer Requested Study or Analysis
Description:
CBS Supplement 1) Determine what are the differences in synaptic composition and microglia activation in the various brain regions involved in cognitive deficits after GCR exposure between male and female.
CBS Supplement 2) Determine what is the genetic signature of microglia in male versus female acutely and chronically after exposure to GCR.
CBS Supplement 3) Is microglia depletion and repopulation able to rescue cognitive deficits in male and female mice after GCR exposure and what are the sex differences in the genetic signature of the repopulated microglia population.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None