Task NSCOR: Progressive Alterations of Central Nervous System Structure and Function Are Caused by Charged Particle Radiation (Completed)
Last Published:  07/30/20 02:45:15 PM (Central)
Short Title: Progressive CNS
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Funding Status: Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
Hypothesis (A) Charged particle irradiation causes a progressive loss of cells and a remodeling of CNS tissue as a function of dose, time and LET. To test hypothesis A we will:
Specific Aim A1. Quantify the cellular composition of mouse brain vascular endothelium using stereological analysis of preserved tissue.
Specific Aim A2. Quantify the composition of mouse neurons, selected glia and stem cells using stereological analysis of preserved tissue.
Specific Aim A3. Quantify the activation of resident and infiltrating mouse immune cells using stereological analysis immune-labeled tissue.
Specific Aim A4. Quantify key molecular biomarkers associated with radiation-induced damage to mouse cells and their microenvironment using targeted gene expression profiling and mutation analysis of a structural gene.
Hypothesis (B) Charged particle irradiation alters the functional output or performance of the brain as a function of dose, time and LET. To test hypothesis B we will:
Specific Aim B1. Quantify tissue-level electrophysiological properties of mouse brain using tissue slices that represent intact regional ensembles of interacting cells. (extracellular, patch clamp)
Specific Aim B2. Map the time evolution of macroscopic structural features and metabolic alteration in mouse brains using MRI.
Hypothesis (C) Exposure to radiation decreases disease latency and alters response to acute stressors. To test hypothesis C we will:
Specific Aim C1. Quantify the magnitude and time course of electrophysiological changes in brain slices of mice expressing a human transgene that produces an Alzheimer disease-like pathology and limits output.
Specific Aim C2. Quantify the electrophysiological performance of brain slices in mice reacting to the application of systemic immune stress using lipopolysaccharide as a surrogate infectious agent
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