Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
Year: 2021
Type: article
Abstract: Radiation-induced cognitive dysfunction is increasingly recognized as an important risk for human exploration of distant planets. Mechanistically-motivated mathematical modeling helps to interpret and quantify this phenomenon. Here we considered two general mechanisms of ionizing radiation-induced damage: targeted effects (TE), caused by traversal of cells by ionizing tracks, and non-targeted effects (NTE), caused by responses of other cells to signals released by traversed cells. We compared the performances of 18 dose response model variants based on these concepts, fitted by robust nonlinear regression to a large published data set on novel object recognition testing in rats exposed to multiple space-relevant radiation types (H, C, O, Si, Ti and Fe ions), covering wide ranges of linear energy transfer (LET) (0.22-181 keV/µm) and dose (0.001-2 Gy). The best-fitting model (based on Akaike information criterion) was an NTE + TE variant where NTE saturate at low doses (~ 0.01 Gy) and occur at all tested LETs, whereas TE depend on dose linearly with a slope that increases with LET. The importance of NTE was also found by additional analyses of the data using quantile regression and random forests. These results suggest that NTE-based radiation effects on brain function are potentially important for astronaut health and for space mission risk assessments.
Source: Scientific Reports
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,990
Awards: THIS PROJECT IS DESIGNED TO USE STATE OF THE ART MECHANISTIC MODELING OF THE EXPERIMENTAL DATA FROM NSCOR PROGRAMS AND OTHER AVAILABLE DATA AS A BASI, FUTURE MISSIONS IN SPACE (SUCH AS A MISSION TO MARS OR THE ESTABLISHMENT OF A MOON BASE) WILL INVOLVE LONG-TERM TRAVEL BEYOND THE MAGNETIC FIELD OF THE EARTH SUBJECTING ASTRONAUTS TO RADIATION HAZARDS POSED BY SOLAR FLARES AND GALACTIC COSMIC RAYS. COSMIC RAYS ARE COMPOSED OF PROTONS ALPHA PARTICLES AND PARTICLES OF HIGH ENERGY AND CHARGE (HZE PARTICLES). PREVIOUS RESEARCH HAS SHOWN THAT EXPOSURE TO SINGLE ABOVE THRESHOLD DOSES OF HZE PARTICLES AND PROTONS CAN AFFECT NEURAL FUNCTIONING AND BEHAVIOR. THESE CHANGES MAY AFFECT THE ABILITY OF ASTRONAUTS TO SUCCESSFULLY MEET MISSION REQUIREMENTS OR MAY PRODUCE DEGENERATIVE CHANGES IN NEURONAL AND BEHAVIORAL FUNCTIONING AFTER THE CONCLUSION OF THE MISSION. THE EFFECTS OF EXPOSURE TO MULTIPLE SUBTHRESHOLD DOSES OF THE SAME ORDIFFERENT PARTICLES OR PROTONS HAVE NOT BEEN EXTENSIVELY STUDIED. THE OBJECTIVES OF THE PROPOSED RESEARCH PROGRAM ARE: (1) TO EVALUATE THE EFFECTS OF REPEATED SUBTHRESHOLD EXPOSURES TO THE SAME AND DIFFERENT HZE PARTICLES AND PROTONS ON COGNITIVE AND NEURONAL DEFICITS AND HOW THEY RELATE TO THE CHARACTERISTICS OF THE SPECIFIC PARTICLE; (2) TO DETERMINE THE RELATIONSHIP BETWEEN CHANGES IN PERFORMANCEAND HZE PARTICLE- AND PROTON-INDUCED CHANGES IN OXIDATIVE STRESS INFLAMMATION SIGNALING MOLECULES AND AUTOPHAGY IN KEY BRAIN REGIONS; AND (3) TO DETERMINE HOW INDIVIDUAL CHARACTERISTICS INCLUDING AGE AND SEX MAY INFLUENCE THE RESPONSIVENESS OF THE INDIVIDUAL TO HZE PARTICLE IRRADIATION.
OpenAlex ID: W3109096889