Last Published:  07/30/20 02:45:15 PM (Central)
Short Title: CNS Mechanisms
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):
Solicited
Aims:

Aim 1: Ascertain the extent that charged particle irradiation elicits acute (2 week) and chronic (1 and 3 month) decrements in cognition dependent on hippocampal, medial prefrontal cortical and neocortical regions of the rodent brain. Determine if/how pharmacologic interventions designed to deplete microglia or inhibit CB1 activity alter cognition following charged particle exposure.


Aim 2: 
Quantify the extent of structural, synaptic, epigenetic and electrophysiologic alterations in neurons from specific regions of the brain following charged particle irradiation with and without specific pharmacologic interventions designed to inhibit CB1 activation.

Aim 3: Elucidate the functional importance of microglia and microglia-derived exosome mediated paracrine interactions in the irradiated brain. Determine how depletion of microglia affects structural and synaptic plasticity following charged particle irradiation. In vitro organotypic and acute slice studies will complement in vivo studies in defining the effect of microglial depletion and how microglia-derived exosome mediated signaling modifies target cell physiology. Additional in vitro studies will define the kinetics of vesicle secretion following irradiation and characterize the functional cargo (mitochondria, protein, mRNA, miRNA).

Resources (None Listed)
Mappings
RiskRisk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
You are here!TaskMechanisms Underlying Charged Particle-Induced Disruption of CNS Function

RiskRisk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
GapBMed-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?
GapBMed-103: What are the validated, efficacious treatments (individual or Team-based) and/or countermeasures to prevent adverse behavioral conditions, CNS/neurological, and/or psychiatric disorders caused by either single and/or integrated exposures to spaceflight hazards during exploration class missions?
GapBMed-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?
You are here!TaskMechanisms Underlying Charged Particle-Induced Disruption of CNS Function

RiskRisk of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure and Secondary Spaceflight Stressors
You are here!TaskMechanisms Underlying Charged Particle-Induced Disruption of CNS Function

RiskRisk of Radiation Carcinogenesis
You are here!TaskMechanisms Underlying Charged Particle-Induced Disruption of CNS Function