Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects

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-...

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Autores principales:	Igor Shuryak, David J. Brenner, Steven R. Blattnig, Barbara Shukitt-Hale, Bernard M. Rabin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69f11dd6a6b7427a98fa119c638239c4
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spelling	oai:doaj.org-article:69f11dd6a6b7427a98fa119c638239c42021-12-02T18:27:47ZModeling space radiation induced cognitive dysfunction using targeted and non-targeted effects10.1038/s41598-021-88486-z2045-2322https://doaj.org/article/69f11dd6a6b7427a98fa119c638239c42021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88486-zhttps://doaj.org/toc/2045-2322Abstract 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.Igor ShuryakDavid J. BrennerSteven R. BlattnigBarbara Shukitt-HaleBernard M. RabinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Igor Shuryak David J. Brenner Steven R. Blattnig Barbara Shukitt-Hale Bernard M. Rabin Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
description	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.
format	article
author	Igor Shuryak David J. Brenner Steven R. Blattnig Barbara Shukitt-Hale Bernard M. Rabin
author_facet	Igor Shuryak David J. Brenner Steven R. Blattnig Barbara Shukitt-Hale Bernard M. Rabin
author_sort	Igor Shuryak
title	Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
title_short	Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
title_full	Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
title_fullStr	Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
title_full_unstemmed	Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
title_sort	modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/69f11dd6a6b7427a98fa119c638239c4
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Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects

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