Short Title:
Astrocytes as CNS Response Mediators to Radiation
Responsible HRP Element:
Space Radiation
Funding Status:
Planned-Funded - Task expected to be within budget
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Procurement Mechanism(s):
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Aims:
Specific Aim 1. Define human astrocyte responses to ionizing radiation. We will map
the dose response and time course of astrocyte responses to X-rays, and 0.5Gy 5-ion simulated
GCRs to identify their relative biological effectiveness (RBE). We will quantify astrocyte gene
expression and correlate it with physiological outcomes: cytokine secretion, cell death and
oxidative stress, to define whether irradiated astrocytes adopt A1 or A2 phenotypes.
Specific Aim 2. Investigate how astrocytes regulate neuronal damage in response to
simulated GCRs. We will utilize 3D CNS TOC models (Mimetas OrganoPlates, Figures 2, 3.)
to define 0.5Gy 5-ion simulated GCR-induced neuronal damage and evaluate the contribution of
astrocytes to regulating it.
Specific Aim 3. Examine whether inducing A1/A2 astrocyte phenotypes could serve
as a countermeasure to simulated GCRs. We will induce TOC astrocyte differentiation into
either A1 or A2 phenotype, and examine whether they exacerbate or inhibit neuronal damage
caused by 0.5Gy simulated GCRs.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
We propose to utilize for the first time a novel high-throughput human tissue-on-a-chip model for 3D neuronal/astrocyte cultures. We will investigate the morphological and physiological outcomes as well as gene expression changes at after simulated space radiation exposure (5-ion simulation of galactic cosmic rays, 500mGy) and compare them to the responses to gamma radiation in order to establish the relative biological effectiveness. We will also evaluate the necessity and sufficiency of astrocytes in regulating radiation responses by establishing experimental models where astrocytes are either the only cell type that is irradiated, or the only cell type that escapes irradiation.Finally, we will test
astrocytes as targets for countermeasures, which has not been done before in the context of spaceflight, and thus could lead to novel breakthroughs.
Internal Customers:
Space Radiation
External Customers:
None