HRR - Task - Molecular and Cellular Mechanisms of Space Radiation-Induced Changes in Hippocampal-Dependent Behavior

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Molecular and Cellular Mechanisms of Space Radiation-Induced Changes in Hippocampal-Dependent Behavior (Completed)

Last Published: 03/26/21 03:34:00 PM (Central)

Task Book: Entry
Principal Investigator: Eisch, Amelia

Short Title: Cellular Hippocampal

Responsible HRP Element: Space Radiation

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

In Aim 1, using behavioral tests with which we have recently published (delayed non-match to pattern radial arm maze for fine spatial distribution; Guo et al., Nat Med 2011), we will explore our hypothesis that space radiation decreases pattern separation in a dose- and LET-dependent manner.
In Aim 2, using transgenic mice we have developed that allow inducible YFP labeling of neural stem cells and their progeny (nestin-CreERT2/R26R mice; Lagace et al., J Neurosci 2007), we will explore our hypothesis that space radiation negatively impacts both adult-generated (Aim 2a) and embryonic-generated (Aim 2b) DG neurons.
In Aim 3, using transgenic mice developed by our colleagues that allow profiling of translating RNA in genetically-defined DG neural cells [BAC-TRAP mice, aka bacterial artificial chromosome translating ribosome affinity purification; Dougherty et al., Cell 2008], we will explore our hypothesis that space radiation causes discrete changes in DG neural cell types in a dose- and LET-dependent manner. Unlike currently used approaches to assess total RNA profiles from cellularly heterogeneous samples (e.g. laser capture dissection and subsequent microarray analysis), the bac-TRAP approach allows purification of specific cell types via ribosome tag and a quantitative comparison of translating RNA profiles in genetically-distinct DG cells (e.g. neural stem cells, adult-generated immature granule cell neurons, and embryonic-generated mature granule cell neurons using BAC-TRAP PBK, DCX, and Cx3Cl1 mouse lines, respectively).

Tissue from Aims 1-3 will be examined using immunohistochemistry, epifluorescent and confocal microscopy, stereologic cell counting, and morphological analysis, and tissue from Aim 3 will be explored using microarrays on the translating RNA pools and qRT-PCR. Taken together, these aims will allow us to test our overall hypothesis that radiation will have distinct, long-lasting effects on the behavioral, cellular, and molecular integrity of the hippocampus. Thus, these results will expedite the quest to estimate CNS radiation risks due to GCR exposure.

Resources (None Listed)

Deliverables (1)

Mappings

Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders

BMed-102: Given exposures to spaceflight hazards (space radiation, isolation), how do we identify individual susceptibility, monitor molecular/biomarkers and acceptable thresholds, and validate behavioral health and CNS/neurological/neuropsychological performance measures and domains of relevance to exploration class missions?

BMed-107: What are the long-term changes and risks to astronaut health post-mission that, when using a continuity of care model, helps retrospectively identify and understand individual susceptibility (e.g., hereditary, dose, thresholds) to mitigate adverse CNS, cognitive, and behavioral health changes resulting from long-duration exploration missions, promoting the behavioral health of current and future crews?

Molecular and Cellular Mechanisms of Space Radiation-Induced Changes in Hippocampal-Dependent Behavior

Related Tasks (271)

Common Item(s)
	Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
	BMed-102: Given exposures to spaceflight hazards (space radiation, isolation), how do we identify individual susceptibility, monitor molecular/biomarkers and acceptable thresholds, and validate behavioral health and CNS/neurological/neuropsychological performance measures and domains of relevance to exploration class missions?
	BMed-107: What are the long-term changes and risks to astronaut health post-mission that, when using a continuity of care model, helps retrospectively identify and understand individual susceptibility (e.g., hereditary, dose, thresholds) to mitigate adverse CNS, cognitive, and behavioral health changes resulting from long-duration exploration missions, promoting the behavioral health of current and future crews?