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ASSESSING THE BIOLOGICAL CONSEQUENCES OF LIVING IN THE SPACE RADIATION ENVIRONMENT REPRESENTS ONE OF THE HIGHEST PRIORITY AREAS OF NASA RESEARCH. OF CRITICAL IMPORTANCE IS THE NEED FOR AN ASSESSMENT OF THE VULNERABILITIES OF THE CENTRAL NERVOUS SYSTEM (CNS) LEADING TO FUNCTIONAL NEUROBEHAVIORAL CHANGES DURING LONG-TERM SPACE MISSIONS AND THE DEVELOPMENT OF EFFECTIVE COUNTERMEASURES TO SUCH RISKS. THE PRESENT PROPOSAL ADDRESSES THIS NEED VIA THE APPLICATION OF AN ANIMAL MODEL TO 1) DETERMINE THE EFFECTS OF ACUTE SINGLE 16O AND 4HE ION EXPOSURES ON SUSTAINED ATTENTION SOCIAL ODOR RECOGNITION MEMORY AND SOCIAL DOMINANCE; 2) DETERMINE THE EFFECTS OF A FRACTIONATED EXPOSURE ON SUSTAINED ATTENTION AND RECOGNITION MEMORY IN COMPARISON TO THE EFFECTS OF SINGLE ION EXPOSURES ON THESE MEASURES 3) DETERMINE THE EFFECTS OF CIRCADIAN DISRUPTIONS AND SLEEP FRAGMENTATION ON SUSTAINED ATTENTION AND RECOGNITION MEMORY FOLLOWING RADIATION EXPOSURE; AND 4) EXAMINE THE UNDERLYING MECHANISMS OF THESE DEFICITS USING IMMUNOHISTOCHEMICAL AND PHARMACOGENETIC PROCEDURES. PRIOR RESEARCH HAS 1) IDENTIFIED RATS THAT ARE SENSITIVE TO RADIATION-INDUCED DEFICITS IN SUSTAINED ATTENTION; AND 2) SHOWN THAT ACUTE SINGLE ION EXPOSURES ALTER SOCIAL MOTIVATION AND SOCIAL ODOR RECOGNITION MEMORY. THE CURRENT PROPOSAL WILL DETERMINE HOW THE IMMEDIATE EFFECTS OF IRRADIATION IMPACT SUBSEQUENT NEUROBEHAVIORAL DEFICITS BY ASSESSING VARIOUS BEHAVIORAL PHYSIOLOGICAL AND NEUROBIOLOGICAL MARKERS OF RADIATION EXPOSURE AT EARLY AND LATER TIME POINTS POST-EXPOSURE. GROUPS OF ANIMALS WILL BE TRAINED ON A RODENT VERSION OF THE HUMAN PSYCHOMOTOR VIGILANCE TEST EXPOSED TO RADIATION AND THEN TESTED FOR BOTH SOCIAL PROCESSING AND SUSTAINED ATTENTION DEFICITS FOLLOWING EXPOSURE; SUBSETS OF RATS WILL BE IMPLANTED WITH BIOTELEMETRY DEVICES TO MEASURE FLUCTUATIONS IN SPONTANEOUS LOCOMOTOR ACTIVITY AND BODY TEMPERATURES FOLLOWING RADIATION EXPOSURE AND CHANGES IN SLEEP OR CIRCADIAN DISRUPTIONS. INDIVIDUAL VARIATIONS IN THESE BEHAVIORAL PHYSIOLOGICAL OR NEUROBIOLOGICAL RESPONSES FOLLOWING RADIATION WILL BE ASSESSED. LIKELY MECHANISMS OF DAMAGE TO THE CNS FOLLOWING RADIATION EXPOSURE WILL BE EXAMINED USING BRAIN TISSUE IN ADDITION TO A PHARMACOGENETIC TECHNIQUE TO DETERMINE THE SEVERITY OF RADIATION-INDUCED NEUROBEHAVIORAL DEFICITS.

$1,396,950FY2020National Aeronautics and Space AdministrationNASA

The Johns Hopkins University

Investigators

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