PMID- 33893378
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20211015
LR  - 20240401
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Apr 23
TI  - Modeling space radiation induced cognitive dysfunction using targeted and 
      non-targeted effects.
PG  - 8845
LID - 10.1038/s41598-021-88486-z [doi]
LID - 8845
AB  - 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/microm) 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.
FAU - Shuryak, Igor
AU  - Shuryak I
AD  - Center for Radiological Research, Columbia University Irving Medical Center, 630 
      West 168th street, VC-11-234/5, New York, NY, 10032, USA. 
      is144@cumc.columbia.edu.
FAU - Brenner, David J
AU  - Brenner DJ
AD  - Center for Radiological Research, Columbia University Irving Medical Center, 630 
      West 168th street, VC-11-234/5, New York, NY, 10032, USA.
FAU - Blattnig, Steven R
AU  - Blattnig SR
AD  - NASA Langley Research Center, Hampton, VA, USA.
FAU - Shukitt-Hale, Barbara
AU  - Shukitt-Hale B
AD  - Human Nutrition Research Center on Aging, USDA-ARS, Tufts University, Boston, MA, 
      USA.
FAU - Rabin, Bernard M
AU  - Rabin BM
AD  - Department of Psychology, University of Maryland Baltimore County, Baltimore, MD, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210423
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
SB  - IM
PMC - PMC8065206
COIS- The authors declare no competing interests.
EDAT- 2021/04/25 06:00
MHDA- 2021/04/25 06:01
PMCR- 2021/04/23
CRDT- 2021/04/24 06:03
PHST- 2020/11/23 00:00 [received]
PHST- 2021/04/13 00:00 [accepted]
PHST- 2021/04/24 06:03 [entrez]
PHST- 2021/04/25 06:00 [pubmed]
PHST- 2021/04/25 06:01 [medline]
PHST- 2021/04/23 00:00 [pmc-release]
AID - 10.1038/s41598-021-88486-z [pii]
AID - 88486 [pii]
AID - 10.1038/s41598-021-88486-z [doi]
PST - epublish
SO  - Sci Rep. 2021 Apr 23;11(1):8845. doi: 10.1038/s41598-021-88486-z.