GGrantIndex
← Search

TASK 1: THE IMPACT OF HZE PARTICLES ON OTHER TESTS IN THE COGNITIVE DOMAIN. USING THE FLEXIBLE BATTERY OF TESTS OFFERED BY THE TOUCHSCREEN OPERANT PLATFORM WE WILL IDENTIFY A BEHAVIORAL FRAMEWORK FOR THE HZE PARTICLE-INDUCED IMPROVEMENT IN PATTERN SEPARATION. WE HYPOTHESIZE HZE PARTICLES WILL IMPROVE PERFORMANCE RELIANT ON HIPPOCAMPAL-CORTICAL INTEGRITY BUT NOT ON STRIATAL-CORTICAL INTEGRITY. A) DETERMINE THE EFFECT OF 0 AND 3X6.7CGY IRON (600 MEV/U) ON THE PERFORMANCE OF MALE 6-9 MONTH OLD (AT TIME OF IRR) C57BL6J MICE ON COGNITIVE BATTERY. IF THESE DATA REVEAL SIGNIFICANT EFFECTS WE WILL ALSO: I. DETERMINE THE EFFECT OF 0 AND 3X6.7CGY IRON (600 MEV/U) ON THE PERFORMANCE OF FEMALE 6-9 MONTH OLD (AT TIME OF IRR) C57BL6J MICE ON COGNITIVE BATTERY II. EXAMINE AN ADDITIONAL GROUP OF MICE FOR 0 AND 0.1 GY IRON (600 MEV/U). B) DETERMINE THE EFFECT OF 0 AND 2X0.1CGY SILICON (275 MEV/U) ON THE PERFORMANCE OF MALE 6-9 MONTH OLD (AT TIME OF IRR) C57BL6J MICE ON COGNITIVE BATTERY. IF THESE DATA REVEAL SIGNIFICANT EFFECTS WE WILL ALSO: I. DETERMINE THE EFFECT OF 0 AND 2X0.1CGY SILICON (275 MEV/U) ON THE PERFORMANCE OF FEMALE 6-9 MONTH OLD (AT TIME OF IRR) C57BL6J MICE ON COGNITIVE BATTERY II. EXAMINE AN ADDITIONAL GROUP OF MICE FOR 0 AND 0.1 GY SILICON (275 MEV/U). TASK 2: THE IMPACT OF HZE PARTICLES ON BEHAVIORS IN THE AFFECTIVE/SOCIAL DOMAIN. PATTERN SEPARATION IS IMPORTANT NOT JUST TO CONTEXTUAL DISCRIMINATION BUT ALSO TO THE RESISTANCE TO MOOD AND ANXIETY DISORDERS. BASED ON THIS AND WITH OUR PREVIOUS EXPERIENCE WITH AN ETHOLOGICALLY-RELEVANT STRESSOR SOCIAL DEFEAT STRESS (SDS) WE WILL TEST HZE PARTICLE-INDUCED INFLUENCE IN THE AFFECTIVE/SOCIAL DOMAIN. WE HYPOTHESIZE THAT IMPROVED PATTERN SEPARATION IS LINKED TO RESILIENCE TO SOCIAL STRESSORS. A) DETERMINE THE EFFECT OF 0 AND 3X6.7CGY IRON (600 MEV/U) ON THE PERFORMANCE OF MALE 6-9 MONTH OLD (AT TIME OF IRR) C57BL6J MICE ON THE SOCIAL INTERACTION TEST (PERFORMED AFTER 10 DAYS OF SDS). I. IF THESE DATA REVEAL SIGNIFICANT EFFECTS WE WILL THEN ALSO EXAMINE AN ADDITIONAL GROUP OF ANIMALS FOR 0 AND 0.1 GY IRON (600 MEV/U). II. IF THESE DATA DO NOT REVEAL SIGNIFICANT EFFECTS WE WILL THEN ASSESS MICE POST- SDS AND SOCIAL INTERACTION FOR ANXIETY AND HEDONIC EFFECTS B) DETERMINE THE EFFECT OF 0 AND 2X0.1CGY SILICON (275 MEV/U) ON THE PERFORMANCE OF MALE 6-9 MONTH OLD (AT TIME OF IRR) C57BL6J MICE ON THE SOCIAL INTERACTION TEST (PERFORMED AFTER 10 DAYS OF SDS). I. IF THESE DATA DO NOT REVEAL SIGNIFICANT EFFECTS WE WILL THEN ASSESS MICE POST- SDS AND SOCIAL INTERACTION FOR ANXIETY AND HEDONIC EFFECTS TASK 3: INDICES OF NEURAL NETWORK PERTURBATION UNDERLYING HZE PARTICLE EXPOSURE- INDUCED IMPROVED PATTERN SEPARATION. WHILE IMPROVED PATTERN SEPARATION HAS BEEN CAUSALLY LINKED TO INCREASED HIPPOCAMPAL NEUROGENESIS [9] OUR DATA SHOW HZE PARTICLE- INDUCED IMPROVEMENT IN PATTERN SEPARATION IS ACTUALLY MARKED BY DECREASED HIPPOCAMPAL NEUROGENESIS. USING CLASSIC (STEREOLOGY OF DENTATE GYRUS INTERNEURON COUNTS) AS WELL AS CUTTING-EDGE TECHNIQUES (RNASEQ) WE WILL TEST THE HYPOTHESIS THAT HZE PARTICLES INFLUENCE THE INTEGRITY OF HIPPOCAMPAL-CORTICAL NEURAL NETWORKS. A) DETERMINE THE EFFECT OF 0 AND 3X6.7CGY IRON (600 MEV/U) ON INTERNEURON NEURON NUMBER AND RNASEQ OF TRANSLATING PROTEINS IN DG GRANULE NEURONS IN MATURE NTF3 BAC-TRAP MICE 3 AND 6 MON POST-IRRADIATION. I. DEPENDING ON THE RESULTS FROM TASK 1A WE MAY THEN ALSO EXAMINE AN ADDITIONAL GROUP OF ANIMALS FOR 0 AND 0.1 GY IRON (600 MEV/U) PROVIDING SUFFICIENT FUNDS REMAIN. B) DETERMINE THE EFFECT OF 0 AND 2X0.1CGY SILICON (275 MEV/U) ON INTERNEURON NEURON NUMBER AND RNASEQ OF TRANSLATING PROTEINS IN DG GRANULE NEURONS IN MATURE NTF3 BAC-TRAP MICE 3 AND 6 MON POST-IRRADIATION. I. DEPENDING ON THE RESULTS FROM TASK 1B WE MAY ALSO DETERMINE THE EFFECT OF 0 AND 2X0.1CGY SILICON (275 MEV/U).

$1,470,094FY2020National Aeronautics and Space AdministrationNASA

The Children'S Hospital Of Philadelphia, Philadelphia PA

Investigators

View source on USAspending →