Task Mechanisms Underlying Charged Particle-Induced Disruption of CNS Function
Last Published:  07/31/19 10:05:33 AM (Central)
Short Title: CNS Mechanisms
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Other:
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).

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Mappings
RiskRisk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
GapCBS-CNS - 1: Are there significant adverse changes in CNS performance in the context and time scale of spaceflight operations? If so, how is significance defined, and which neuropsychological domains are affected? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?
GapCBS-CNS - 2: Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?
GapCBS-CNS - 3: How does individual susceptibility including hereditary pre-disposition (e.g. Alzheimer’s, Parkinson’s, apoE allele) and prior CNS injury (e.g. concussion, chronic inflammation or other) alter significant CNS risks? Does individual susceptibility modify possible threshold doses for these risks in a significant way?
GapCBS-CNS - 5: How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE?
GapCNS - 6: How can new knowledge and data from molecular, cellular, tissue and animal models of late CNS risks or clinical human data be used to estimate late CNS risks to astronauts from GCR and SPE?
You are here!TaskMechanisms Underlying Charged Particle-Induced Disruption of CNS Function

RiskRisk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
GapCBS-CNS - 1: Are there significant adverse changes in CNS performance in the context and time scale of spaceflight operations? If so, how is significance defined, and which neuropsychological domains are affected? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?
GapCBS-CNS - 2: Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?
GapCBS-CNS - 3: How does individual susceptibility including hereditary pre-disposition (e.g. Alzheimer’s, Parkinson’s, apoE allele) and prior CNS injury (e.g. concussion, chronic inflammation or other) alter significant CNS risks? Does individual susceptibility modify possible threshold doses for these risks in a significant way?
GapCBS-CNS - 5: How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE?
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