560
Views
0
CrossRef citations to date
0
Altmetric
Articles

Consequences of space radiation on the brain and cardiovascular system

, &

References

  • Norbury JW, Schimmerling W, Slaba TC, et al. Galactic cosmic ray simulation at the NASA Space Radiation Laboratory. Life Sci Space Res (Amst). 2016;8:38–51. doi:10.1016/j.lssr.2016.02.001.
  • Cucinotta FA. Space radiation risks for astronauts on multiple international space station missions. PLoS One. 2014;9(4):e96099. doi:10.1371/journal.pone.0096099.
  • Bouillon K, Haddy N, Delaloge S, et al. Long-term cardiovascular mortality after radiotherapy for breast cancer. J Am Coll Cardiol. 2011;57(4):445–452. doi:10.1016/j.jacc.2010.08.638.
  • Sardar P, Kundu A, Chatterjee S, et al. Long-term cardiovascular mortality after radiotherapy for breast cancer: a systematic review and meta-analysis. Clin Cardiol. 2017;40(2):73–81. doi:10.1002/clc.22631.
  • Adams H, Martin W, Wilson A, Palmer S. Radiation therapy induced cardiovascular disease. Hear Vessel Transplant. 2017;25:82–89. doi:10.24969/hvt.2017.25.
  • Simonsen LC, Slaba TC, Guida P, Rusek A. NASA’s first ground-based galactic cosmic ray simulator: enabling a new era in space radiobiology research. PLoS Biol 2020;18(5):e300669. doi:10.1371/journal.pbio.3000669.
  • Andersen P, Morris R, Amaral D, Bliss T, O’Keefe J. The Hippocampus Book. Oxford, UK: Oxford University Press. 2009. doi:10.1093/acprof:oso/9780195100273.001.0001.
  • Bramham CR. Local protein synthesis, actin dynamics, and LTP consolidation. Curr Opin Neurobiol. 2008;18(5):524–531. doi:10.1016/j.conb.2008.09.013.
  • Kempermann G, Gast D, Kronenberg G, Yamaguchi M, Gage FH. Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development. 2003;130(2):391–399. doi:10.1242/dev.00203.
  • Eriksson PS, Perfilieva E, Björk-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4(11):1313–1317. doi:10.1038/3305.
  • Kuhn HG, Dickinson-Anson H, Gage FH. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci. 1996;16(6):2027–2033. doi:10.1523/JNEUROSCI.16-06-02027.1996.
  • Kempermann G, Jessberger S, Steiner B, Kronenberg G. Milestones of neuronal development in the adult hippocampus. Trends Neurosci. 2004;27(8):447–452. doi:10.1016/j.tins.2004.05.013.
  • Markakis EA, Gage FH. Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles. J Comp Neurol. 1999;406(4):449–460. doi:10.1002/(SICI)1096-9861(19990419)406:4 < 449::AID-CNE3 > 3.0.CO;2-I.
  • van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH. Functional neurogenesis in the adult hippocampus. Nature. 2002;415(6875):1030–1034. doi:10.1038/4151030a.
  • Van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999;96(23):13427–13431. doi:10.1073/pnas.96.23.13427.
  • Raber J, Fan Y, Matsumori Y, et al. Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits. Ann Neurol. 2004;55(3):381–389. doi:10.1002/ana.10853.
  • Madsen TM, Kristjansen PEG, Bolwig TG, Wörtwein G. Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat. Neuroscience. 2003;119(3):635–642. doi:10.1016/S0306-4522(03)00199-4.
  • Monje ML, Mizumatsu S, Fike JR, Palmer TD. Irradiation induces neural precursor-cell dysfunction. Nat Med. 2002;8(9):955–962. doi:10.1038/nm749.
  • Mizumatsu S, Monje ML, Morhardt DR, Rola R, Palmer TD, Fike JR. Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res. 2003;63(14):4021–4027.
  • Rola R, Otsuka S, Obenaus A, et al. Indicators of hippocampal neurogenesis are altered by 56Fe-particle irradiation in a dose-dependent manner. Radiat Res. 2004;162(4):442–446. doi:10.1667/RR3234.
  • Rola R, Zou Y, Huang TT, et al. Lack of extracellular superoxide dismutase (EC-SOD) in the microenvironment impacts radiation-induced changes in neurogenesis. Free Radic Biol Med. 2007;42(8):1133–1145. doi:10.1016/j.freeradbiomed.2007.01.020.
  • Raber J, Rola R, LeFevour A, et al. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat Res. 2004;162(1):39–47. doi:10.1667/RR3206.
  • Rola R, Raber J, Rizk A, et al. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol. 2004;188(2):316–330. doi:10.1016/j.expneurol.2004.05.005.
  • Rola R, Fishman K, Baure J, et al. Hippocampal neurogenesis and neuroinflammation after cranial irradiation with (56)Fe particles. Radiat Res. 2008;169(6):626–632. doi:10.1667/RR1263.1.
  • Sweet TB, Panda N, Hein AM, et al. Central nervous system effects of whole-body proton irradiation. Radiat Res. 2014;182(1):18–34. doi:10.1667/RR13699.1.
  • Cucinotta FA, Durante M. Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings. Lancet Oncol. 2006;7(5):431–435. doi:10.1016/S1470-2045(06)70695-7.
  • Rivera PD, Shih HY, Leblanc JA, et al. Acute and fractionated exposure to High-LET 56Fe HZE-particle radiation both result in similar long-term deficits in adult hippocampal neurogenesis. Radiat Res. 2013;180(6):658–667. doi:10.1667/RR13480.1.
  • Whoolery CW, Walker AK, Richardson DR, et al. Whole-body exposure to 28Si-radiation dose-dependently disrupts dentate gyrus neurogenesis and proliferation in the short term and new neuron survival and contextual fear conditioning in the long term. Radiat Res. 2017;188(5):532–551. doi:10.1667/RR14797.1.
  • Decarolis NA, Rivera PD, Ahn F, et al. 56Fe particle exposure results in a long-lasting increase in a cellular index of genomic instability and transiently suppresses adult hippocampal neurogenesis in vivo. Life Sci Space Res (Amst). 2014;2:70–79. doi:10.1016/j.lssr.2014.06.004.
  • Stuart GJ, Spruston N. Dendritic integration: 60 years of progress. Nat Neurosci. 2015;18(12):1713–1721. doi:10.1038/nn.4157.
  • Kulkarni VA, Firestein BL. The dendritic tree and brain disorders. Mol Cell Neurosci. 2012;50(1):10–20. doi:10.1016/j.mcn.2012.03.005.
  • Koleske AJ. Molecular mechanisms of dendrite stability. Nat Rev Neurosci. 2013;14(8):536–550. doi:10.1038/nrn3486.
  • Zaqout S, Kaindl AM. Golgi-cox staining step by step. Front Neuroanat. 2016;10:1–7. doi:10.3389/fnana.2016.00038.
  • Carr H, Alexander TC, Groves T, et al. Early effects of 16O radiation on neuronal morphology and cognition in a murine model. Life Sci Space Res (Amst). 2018;17:63–73. doi:10.1016/j.lssr.2018.03.001.
  • Kiffer F, Howe AK, Carr H, et al. Late effects of 1 H irradiation on hippocampal physiology. Life Sci Sp Res. 2018;17:51–62. doi:10.1016/j.lssr.2018.03.004.
  • Allen AR, Raber J, Chakraborti A, Sharma S, Fike JR. 56Fe irradiation alters spine density and dendritic complexity in the mouse hippocampus. Radiat Res. 2015;184(6):586–594. doi:10.1667/RR14103.1.
  • Parihar VK, Pasha J, Tran KK, Craver BM, Acharya MM, Limoli CL. Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation. Brain Struct Funct. 2015;220(2):1161–1171. doi:10.1007/s00429-014-0709-9.
  • Cohen SJ, Stackman RW. Assessing rodent hippocampal involvement in the novel object recognition task. A review. Behav Brain Res. 2015;285:105–117. doi:10.1016/j.bbr.2014.08.002.
  • Broadbent NJ, Gaskin S, Squire LR, Clark RE. Object recognition memory and the rodent hippocampus. Learn Mem. 2010;17(1):5–800. doi:10.1101/lm.1650110.
  • Parihar VK, Allen B, Tran KK, et al. What happens to your brain on the way to Mars. Sci Adv. 2015;1(4):e1400256-e1400256. doi:10.1126/sciadv.1400256.
  • Rabin BM, Shukitt-Hale B, Carrihill-Knoll KL, Gomes SM. Comparison of the effects of partial- or whole-body exposures to 16O particles on cognitive performance in rats. Radiat Res. 2014;181(3):251–257. doi:10.1667/RR13469.1.
  • Rabin BM, Poulose SM, Carrihill-Knoll KL, et al. Acute effects of exposure to (56)Fe and (16)O Particles on Learning and Memory. Radiat Res. 2015;184(2):143–150. doi:10.1667/RR13935.1.
  • Howe A, Kiffer F, Alexander TC, et al. Long-term changes in cognition and physiology after low-dose 16 O irradiation. IJMS. 2019;20(1):188. doi:10.3390/ijms20010188.
  • Kiffer F, Alexander T, Anderson JE, et al. Late effects of 16 O-particle radiation on female social and cognitive behavior and hippocampal physiology. Radiat Res. 2019;191(3):278–294. doi:10.1667/RR15092.1.
  • Raber J, Torres ERS, Akinyeke T, et al. Detrimental effects of helium ion irradiation on cognitive performance and cortical levels of MAP-2 in B6D2F1 mice. IJMS. 2018;19(4):1247. doi:10.3390/ijms19041247.
  • Nelson GA. Space radiation and human exposures, a primer. Radiat Res. 2016;185(4):349–358. doi:10.1667/RR14311.1.
  • Krukowski K, Feng X, Paladini MS, et al. Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits. Sci Rep. 2018;8(1):1–13. doi:10.1038/s41598-018-26039-7.
  • Rabin BM, Poulose SM, Bielinski DF, Shukitt-Hale B. Effects of head-only or whole-body exposure to very low doses of 4 He (1000 MeV/n) particles on neuronal function and cognitive performance. Life Sci Sp Res. 2019;20:85–92. doi:10.1016/j.lssr.2019.02.001.
  • Parihar VK, Allen BD, Tran KK, et al. Targeted overexpression of mitochondrial catalase prevents radiation-induced cognitive dysfunction. Antioxid Redox Signal. 2015;22(1):78–91. doi:10.1089/ars.2014.5929.
  • Bellone JA, Rudobeck E, Hartman RE, Szücs A, Vlkolinský R. A single low dose of proton radiation induces long-term behavioral and electrophysiological changes in mice. Radiat Res. 2015;184(2):193–202. doi:10.1667/RR13903.1.
  • Shukitt-Hale B, Szprengiel A, Pluhar J, Rabin BM, Joseph JA. The effects of proton exposure on neurochemistry and behavior. Adv Sp Res. 2004;33(8):1334–1339. doi:10.1016/j.asr.2003.10.038.
  • Dulcich MS, Hartman RE. Pomegranate supplementation improves affective and motor behavior in mice after radiation exposure. Evidence-Based Complement Altern Med. 2013;2013:1–8. doi:10.1155/2013/940830.
  • Rabin BM, Buhler LL, Joseph JA, Shukitt-Hale B, Jenkins DG. Effects of exposure to 56Fe particles or protons on fixed-ratio operant responding in rats. JRR. 2002;43(S):S225–S228. doi:10.1269/jrr.43.S225.
  • Shukitt-Hale B, Casadesus G, McEwen JJ, Rabin BM, Joseph JA. Spatial learning and memory deficits induced by exposure to iron-56- particle radiation. Radiat Res. 2000;154(1):28–33.[0028:SLAMDI]2.0.CO;2. doi:10.1667/0033-7587(2000)154.[10.1667/0033-7587(2000)154[0028:SLAMDI]2.0.CO;2]
  • Shukitt-Hale B, Carey AN, Jenkins D, Rabin BM, Joseph JA. Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging. Neurobiol Aging. 2007;28(8):1187–1194. doi:10.1016/j.neurobiolaging.2006.05.031.
  • Britten RA, Jewell JS, Miller VD, Davis LK, Hadley MM, Wyrobek AJ. Impaired spatial memory performance in adult wistar rats exposed to low (5–20 cGy) doses of 1 GeV/n 56 Fe particles. Radiat Res. 2016;185(3):332–337. doi:10.1667/RR14120.1.
  • Britten RA, Davis LK, Johnson AM, et al. Low (20 cGy) Doses of 1 GeV/u (56)Fe-particle radiation lead to a persistent reduction in the spatial learning ability of rats. Radiat Res. 2012;177(2):146–151. doi:10.1667/rr2637.1.
  • Denisova NA, Shukitt-Hale B, Rabin BM, Joseph JA. Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation. Radiat Res. 2002;158(6):725–734. doi:10.1667/0033-7587(2002)158[0725:BSABRI]2.0.CO;2.2.0.co;2]
  • Villasana LE, Rosenthal RA, Doctrow SR, et al. Effects of alpha-lipoic acid on associative and spatial memory of sham-irradiated and 56Fe-irradiated C57BL/6J male mice. Pharmacol Biochem Behav. 2013;103(3):487–493. doi:10.1016/j.pbb.2012.09.021.
  • Raber J, Allen AR, Sharma S, et al. Effects of proton and combined proton and (56)Fe radiation on the hippocampus. Radiat Res. 2016;185(1):20–30. doi:10.1667/RR14222.1.
  • Lampe N, Breton V, Sarramia D, Sime-Ngando T, Biron DG. Understanding low radiation background biology through controlled evolution experiments. Evol Appl. 2017;10(7):658–666. doi:10.1111/eva.12491.
  • Krukowski K, Grue K, Frias ES, et al. Female mice are protected from space radiation-induced maladaptive responses. Brain Behav Immun. 2018;74:106–120. doi:10.1016/j.bbi.2018.08.008.
  • Kiffer F, Carr H, Groves T, et al. Effects of 1H + 16O charged particle irradiation on short-term memory and hippocampal physiology in a murine model. Radiat Res. 2018;189(1):53–63. doi:10.1667/RR14843.1.
  • Kiffer F, Alexander T, Anderson J, et al. Late effects of 1H + 16O on short-term and object memory, hippocampal dendritic morphology and mutagenesis. Front Behav Neurosci. 2020;14:1–15. doi:10.3389/fnbeh.2020.00096.
  • Schafer DP, Lehrman EK, Kautzman AG, et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012;74(4):691–705. doi:10.1016/j.neuron.2012.03.026.
  • Stollg G, Jander S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol. 1999;58(3):233–247. doi:10.1016/S0301-0082(98)00083-5.
  • Loane DJ, Byrnes KR. Role of microglia in neurotrauma. Neurotherapeutics. 2010;7(4):366–377. doi:10.1016/j.nurt.2010.07.002.
  • Joo KM, Jin J, Kang BG, et al. Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage. PLoS One. 2012;7(2):e25936. doi:10.1371/journal.pone.0025936.
  • Gridley DS, Pecaut MJ. Whole-body irradiation and long-term modification of bone marrow-derived cell populations by low- and high-LET radiation. In Vivo (Brooklyn). 2006;20(6 B):781–790.
  • Kim S, Chung H, Mai HN, et al. Low-dose ionizing radiation modulates microglia phenotypes in the models of Alzheimer’s disease. Int J Mol Sci. 2020;21(12):1–18. doi:10.3390/ijms21124532.
  • Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007;8(1):57–69. doi:10.1038/nrn2038.
  • Rola R, Sarkissian V, Obenaus A, et al. High-LET radiation induces inflammation and persistent changes in markers of hippocampal neurogenesis. Radiat Res. 2005;164(4 Pt 2):556–560. doi:10.1667/RR3412.1.
  • Encinas JM, Vazquez ME, Switzer RC, et al. Quiescent adult neural stem cells are exceptionally sensitive to cosmic radiation. Exp Neurol. 2008;210(1):274–279. doi:10.1016/j.expneurol.2007.10.021.
  • Allen BD, Syage AR, Maroso M, et al. Mitigation of helium irradiation-induced brain injury by microglia depletion. J Neuroinflammation. 2020;17(1):159. doi:10.1186/s12974-020-090-9.
  • Roberts AC, Clarke HF. Why we need nonhuman primates to study the role of ventromedial prefrontal cortex in the regulation of threat- And reward-elicited responses. Proc Natl Acad Sci USA. 2019;116(52):26297–26304. doi:10.1073/pnas.1902288116.
  • Laubach M, Amarante LM, Swanson K, White SR. What, if anything, is rodent prefrontal cortex? eNeuro. 2018;5(5):333. doi:10.1523/ENEURO.0315-18.2018.
  • Wallis JD. Cross-species studies of orbitofrontal cortex and value-based decision-making. Nat Neurosci. 2011;15(1):13–19. doi:10.1038/nn.2956.
  • Euston DR, Gruber AJ, McNaughton BL. The role of medial prefrontal cortex in memory and decision making. Neuron. 2012;76(6):1057–1070. doi:10.1016/j.neuron.2012.12.002.
  • Britten RA, Miller VD, Hadley MM, Jewell JS, Macadat E. Performance in hippocampus- and PFC-dependent cognitive domains are not concomitantly impaired in rats exposed to 20 cGy of 1 GeV/n 56 Fe particles. Life Sci Sp Res. 2016;10:17–22. doi:10.1016/j.lssr.2016.06.005.
  • Britten RA, Duncan VD, Fesshaye A, Rudobeck E, Nelson GA, Vlkolinsky R. Altered cognitive flexibility and synaptic plasticity in the rat prefrontal cortex after exposure to low (≤15 cGy) doses of 28Si radiation. Radiat Res. 2020;193(3):223–235. doi:10.1667/RR15458.1.
  • Mange A, Cao Y, Zhang S, Hienz RD, Davis CM. Whole-body oxygen (16O) ion-exposure-induced impairments in social odor recognition memory in rats are dose and time dependent. Radiat Res. 2018;189(3):292–299. doi:10.1667/RR14849.1.
  • Jones CB, Mange A, Granata L, Johnson B, Hienz RD, Davis CM. Short and long-term changes in social odor recognition and plasma cytokine levels following oxygen (16 o) ion radiation exposure. IJMS. 2019;20(2):339. doi:10.3390/ijms20020339.
  • Krukowski K, Jones T, Campbell-Beachler M, Nelson G, Rosi S. Peripheral T cells as a biomarker for oxygen-ion-radiation-induced social impairments. Radiat Res. 2018;190(2):186–193. doi:10.1667/RR15046.1.
  • Acharya MM, Baulch JE, Klein PM, et al. New concerns for neurocognitive function during deep space exposures to chronic, low dose-rate, neutron radiation. eNeuro. 2019;6(4):ENEURO.0094-19.2019. doi:10.1523/ENEURO.0094-19.2019.
  • Parihar VK, Allen B, Tran KK, et al. What happens to your brain on the way to Mars. Sci Adv. 2015;1:e1400256. doi:10.1126/sciadv.1400256.
  • Parihar VK, Allen BD, Caressi C, et al. Cosmic radiation exposure and persistent cognitive dysfunction. Sci Rep. 2016;6(1):e34774. doi:10.1038/srep34774.
  • Parihar VK, Maroso M, Syage A, et al. Persistent nature of alterations in cognition and neuronal circuit excitability after exposure to simulated cosmic radiation in mice. Exp Neurol. 2018;305:44–55. doi:10.1016/j.expneurol.2018.03.009.
  • Lonart G, Parris B, Johnson AM, et al. Executive function in rats is impaired by low (20 cGy) doses of 1 GeV/u 56Fe particles. Radiat Res. 2012;178(4):289–294. doi:10.1667/RR2862.1.
  • Britten RA, Davis LK, Jewell JS, et al. Exposure to mission relevant doses of 1 GeV/nucleon (56)Fe particles leads to impairment of attentional set-shifting performance in socially mature rats. Radiat Res. 2014;182(3):292–298. doi:10.1667/rr3766.1.
  • Davis CM, DeCicco-Skinner KL, Hienz RD. Deficits in sustained attention and changes in dopaminergic protein levels are related to basal dopaminergic function. PLoS One. 2015;10(12):e0144556.. doi:10.1371/journal.pone.0144556.
  • Belov OV, Belokopytova KV, Kudrin VS, Molokanov AG, Shtemberg AS, Bazyan AS. Neurochemical insights into the radiation protection of astronauts: distinction between low- and moderate-LET radiation components. Phys Medica. 2019;57:7–16. doi:10.1016/j.ejmp.2018.12.003.
  • Raber J, Rudobeck E, Campbell-Beachler M, et al. 28Silicon radiation-induced enhancement of synaptic plasticity in the hippocampus of naïve and cognitively tested mice. Radiat Res. 2014;181(4):362–368. doi:10.1667/RR13347.1.
  • Katzman A, Alberini CM. NLGN1 and NLGN2 in the prefrontal cortex: their role in memory consolidation and strengthening. Curr Opin Neurobiol. 2018;48:122–130. doi:10.1016/j.conb.2017.12.003.
  • Kugelman T, Zuloaga DG, Weber S, Raber J. Post-training gamma irradiation-enhanced contextual fear memory associated with reduced neuronal activation of the infralimbic cortex. Behav Brain Res. 2016;298:1–11. doi:10.1016/j.bbr.2015.10.050.
  • Kokhan VS, Anokhin PK, Belov OV, Gulyaev MV. Cortical glutamate/GABA imbalance after combined radiation exposure: relevance to human deep-space missions. Neuroscience. 2019;416:295–308. doi:10.1016/j.neuroscience.2019.08.009.
  • Yizhar O, Fenno LE, Prigge M, et al. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature. 2011;477(7363):171–178. doi:10.1038/nature10360.
  • Durieux AMS, Horder J, Petrinovic MM. Neuroligin-2 and the tightrope of excitation/inhibition balance in the prefrontal cortex. J Neurophysiol. 2016;115(1):5–7. doi:10.1152/jn.00703.2015.
  • Van Zandt M, Weiss E, Almyasheva A, Lipior S, Maisel S, Naegele JR. Adeno-associated viral overexpression of neuroligin 2 in the mouse hippocampus enhances GABAergic synapses and impairs hippocampal-dependent behaviors. Behav Brain Res. 2019;362:7–20. doi:10.1016/j.bbr.2018.12.052.
  • Liang J, Xu W, Hsu YT, Yee AX, Chen L, Südhof TC. Conditional neuroligin-2 knockout in adult medial prefrontal cortex links chronic changes in synaptic inhibition to cognitive impairments. Mol Psychiatry. 2015;20(7):850–859. doi:10.1038/mp.2015.31.
  • Robinson S, Granata L, Hienz RD, Davis CM. Temporary inactivation of the medial prefrontal cortex impairs the formation, but not the retrieval of social odor recognition memory in rats. Neurobiol Learn Mem. 2019;161:115–121. doi:10.1016/j.nlm.2019.04.003.
  • Robbins ME, Bourland JD, Cline JM, Wheeler KT, Deadwyler SA. A model for assessing cognitive impairment after fractionated whole-brain irradiation in nonhuman primates. Radiat Res. 2011;175(4):519–525. doi:10.1667/RR2497.1.
  • Mark S, Scott GBI, Donoviel DB, et al. The impact of sex and gender on adaptation to space: a NASA decadal review the impact of sex and gender on adaptation to space: executive summary. J Womens Health (Larchmt). 2014;23(11):941–947. doi:10.1089/jwh.2014.4914.
  • Reschke MF, Cohen HS, Cerisano JM, et al. Effects of sex and gender on adaptation to space: neurosensory systems. J Womens Health (Larchmt). 2014;23(11):959–962. doi:10.1089/jwh.2014.4908.
  • Haley GE, Yeiser L, Olsen RHJ, Davis MJ, Johnson LA, Raber J. Early effects of whole-body 56Fe irradiation on hippocampal function in C57BL/6J mice. Radiat Res. 2013;179(5):590–596. doi:10.1667/RR2946.1.
  • Raber J, Weber SJ, Kronenberg A, Turker MS. Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training. Life Sci Sp Res. 2016;9:56–61. doi:10.1016/j.lssr.2016.03.002.
  • Raber J, Yamazaki J, Torres ERS, et al. Combined effects of three high-energy charged particle beams important for space flight on brain, behavioral and cognitive endpoints in B6D2F1 female and male mice. Front Physiol. 2019;10:179. doi:10.3389/fphys.2019.00179.
  • Owlett L, Belcher EK, Dionisio-Santos DA, Williams JP, Olschowka JA, O’Banion MK. Space radiation does not alter amyloid or tau pathology in the 3xTg mouse model of Alzheimer’s disease. Life Sci Sp Res. 2020;27:89–98. doi:10.1016/j.lssr.2020.08.001.
  • Villasana L, Rosenberg J, Raber J. Sex-dependent effects of 56Fe irradiation on contextual fear conditioning in C57BL/6J mice. Hippocampus. 2010;20(1):19–23. doi:10.1002/hipo.20659.
  • Villasana LE, Benice TS, Raber J. Long-term effects of 56Fe irradiation on spatial memory of mice: role of sex and apolipoprotein e isoform. Int J Radiat Oncol Biol Phys. 2011;80(2):567–573. doi:10.1016/j.ijrobp.2010.12.034.
  • Villasana L, Dayger C, Raber J. Dose- and ApoE isoform-dependent cognitive injury after cranial 56Fe irradiation in female mice. Radiat Res. 2013;179(4):493–500. doi:10.1667/RR3210.1.
  • Pecaut MJ, Haerich P, Zuccarelli CN, Smith AL, Zendejas ED, Nelson GA. Behavioral consequences of radiation exposure to simulated space radiation in the C57BL/6 mouse: open field, rotorod, and acoustic startle. Cogn Affect Behav Neurosci. 2002;2(4):329–340. doi:10.3758/CABN.2.4.329.
  • Pecaut MJ, Haerich P, Zuccarelli Miller CN, Smith AL, Zendejas ED, Nelson GA. The effects of low-dose, high-LET radiation exposure on three models of behavior in C57BL/6 mice. Radiat Res. 2004;162(2):148–156. doi:10.1667/RR3205.
  • Perez RE, Younger S, Bertheau E, Fallgren CM, Weil MM, Raber J. Effects of chronic exposure to a mixed field of neutrons and photons on behavioral and cognitive performance in mice. Behav Brain Res. 2020;379:112377. doi:10.1016/j.bbr.2019.112377.
  • Rabin BM, Miller MG, Larsen A, et al. Effects of exposure to 12C and 4He particles on cognitive performance of intact and ovariectomized female rats. Life Sci Sp Res (Amst). 2019;22:47–54. doi:10.1016/j.lssr.2019.07.005.
  • Rabin BM, Carrihill-Knoll KL, Long LV, Pitts SC, Hale BS. Effects of 17β-estradiol on cognitive performance of ovariectomized female rats exposed to space radiation. JBBS. 2013;3(1):67–73. doi:10.4236/jbbs.2013.31007.
  • Davis CM, Decicco-Skinner KL, Roma PG, Hienz RD. Individual differences in attentional deficits and dopaminergic protein levels following exposure to proton radiation. Radiat Res. 2014;181(3):258–271. doi:10.1667/RR13359.1.
  • Basner M, Dinges DF, Mollicone DJ, et al. Psychological and behavioral changes during confinement in a 520-day simulated interplanetary mission to mars. PLoS One. 2014;9(3):e93298. doi:10.1371/journal.pone.0093298.
  • Delp MD, Charvat JM, Limoli CL, Globus RK, Ghosh P. Apollo lunar astronauts show higher cardiovascular disease mortality: possible deep space radiation effects on the vascular endothelium. Sci Rep. 2016;6(1):e29901. doi:10.1038/srep29901.
  • Cucinotta FA, Hamada N, Little MP. No evidence for an increase in circulatory disease mortality in astronauts following space radiation exposures. Life Sci Space Res (Amst). 2016;10:53–56. doi:10.1016/j.lssr.2016.08.002.
  • Elgart SR, Little MP, Chappell LJ, et al. Radiation exposure and mortality from cardiovascular disease and cancer in early NASA astronauts. Sci Rep. 2018;8(1):8480. doi:10.1038/s41598-018-25467-9.
  • Reynolds RJ, Bukhtiyarov IV, Tikhonova GI, Day SM, Ushakov IB, Gorchakova TYU. Contrapositive logic suggests space radiation not having a strong impact on mortality of US astronauts and Soviet and Russian cosmonauts. Sci Rep. 2019;9(1):8583. doi:10.1038/s41598-019-44858-0.
  • Yong LC, Pinkerton LE, Yiin JH, Anderson JL, Deddens JA. Mortality among a cohort of U.S. commercial airline cockpit crew. Am J Ind Med. 2014;57(8):906–914. doi:10.1002/ajim.22318.
  • Hammer GP, Auvinen A, De Stavola BL, et al. Mortality from cancer and other causes in commercial airline crews: a joint analysis of cohorts from 10 countries. Occup Environ Med. 2014;71(5):313–322. doi:10.1136/oemed-2013-101395.
  • Blettner M, Zeeb H, Auvinen A, et al. Mortality from cancer and other causes among male airline cockpit crew in Europe. Int J Cancer. 2003;106(6):946–952. doi:10.1002/ijc.11328.
  • Seawright JW, Sridharan V, Landes RD, et al. Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice. Life Sci Sp Res. 2019;20:72–84. doi:10.1016/j.lssr.2019.01.003.
  • Soucy KG, Lim HK, Kim JH, et al. HZE 56Fe-ion irradiation induces endothelial dysfunction in rat aorta: role of xanthine oxidase. Radiat Res. 2011;176(4):474–485. doi:10.1667/rr2598.1.
  • Sridharan V, Seawright JW, Landes RD, et al. Effects of single-dose protons or oxygen ions on function and structure of the cardiovascular system in male Long Evans rats. Life Sci Space Res (Amst). 2020;26:62–68. doi:10.1016/j.lssr.2020.04.002.
  • Amino M, Yoshioka K, Fujibayashi D, et al. Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation. Am J Physiol - Hear Circ Physiol. 2010;298(3):H1014–H1021. doi:10.1152/ajpheart.00160.2009.
  • Sasi SP, Yan X, Zuriaga-Herrero M, et al. Different sequences of fractionated low-dose proton and single iron-radiation-induced divergent biological responses in the heart. Radiat Res. 2017;188(2):191–203. doi:10.1667/RR14667.1.
  • Yan X, Sasi SP, Gee H, et al. Cardiovascular risks associated with low dose ionizing particle radiation. PLoS One. 2014;9(10):e110269. doi:10.1371/journal.pone.011026.
  • Yu T, Parks BW, Yu S, et al. Iron-ion radiation accelerates atherosclerosis in apolipoprotein E-Deficient mice. Radiat Res. 2011;175(6):766–773. doi:10.1667/RR2482.1.
  • Amino M, Yoshioka K, Tanabe T, et al. Heavy ion radiation up-regulates Cx43 and ameliorates arrhythmogenic substrates in hearts after myocardial infarction. Cardiovasc Res. 2006;72(3):412–421. doi:10.1016/j.cardiores.2006.09.010.
  • Zurita E, Chagoyen M, Cantero M, et al. Genetic polymorphisms among C57BL/6 mouse inbred strains. Transgenic Res. 2011;20(3):481–489. doi:10.1007/s11248-010-9403-8.
  • Heselich A, Frieß JL, Ritter S, Benz NP, Layer PG, Thielemann C. High LET radiation shows no major cellular and functional effects on primary cardiomyocytes in vitro. Life Sci Space Res (Amst). 2018;16:93–100. doi:10.1016/j.lssr.2018.01.001.
  • Baselet B, Azimzadeh O, Erbeldinger N, et al. Differential impact of single-dose Fe ion and X-ray irradiation on endothelial cell transcriptomic and proteomic responses. Front Pharmacol. 2017;8:570. doi:10.3389/fphar.2017.00570.
  • Beck M, Rombouts C, Moreels M, et al. Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation. Int J Mol Med. 2014;34(4):1124–1132. doi:10.3892/ijmm.2014.1893.
  • Grabham P, Hu B, Sharma P, Geard C. Effects of ionizing radiation on three-dimensional human vessel models: differential effects according to radiation quality and cellular development. Radiat Res. 2011;175(1):21–28. doi:10.1667/RR2289.1.
  • Ramadan SS, Sridharan V, Koturbash I, et al. A priming dose of protons alters the early cardiac cellular and molecular response to (56)Fe irradiation. Life Sci Space Res (Amst). 2016;8:8–13. doi:10.1016/j.lssr.2015.12.001.
  • Tungjai M, Whorton EB, Rithidech KN. Persistence of apoptosis and inflammatory responses in the heart and bone marrow of mice following whole-body exposure to 28Silicon (28Si) ions. Radiat Environ Biophys. 2013;52(3):339–350. doi:10.1007/s00411-013-0479-4.
  • Miousse IR, Skinner CM, Sridharan V, et al. Changes in one-carbon metabolism and DNA methylation in the hearts of mice exposed to space environment-relevant doses of oxygen ions (16O). Life Sci Space Res (Amst)). 2019;22:8–15. doi:10.1016/j.lssr.2019.05.003.
  • Koturbash I, Miousse IR, Sridharan V, et al. Radiation-induced changes in DNA methylation of repetitive elements in the mouse heart. Mutat Res. 2016;787:43–53. doi:10.1016/j.mrfmmm.2016.02.009.
  • Beheshti A, McDonald JT, Miller J, Grabham P, Costes SV. Genelab database analyses suggest long-term impact of space radiation on the cardiovascular system by the activation of FYN through reactive oxygen species. IJMS. 2019;20(3):661. doi:10.3390/ijms20030661.
  • Logan RW, Robledo RF, Recla JM, et al. High-precision genetic mapping of behavioral traits in the diversity outbred mouse population. Genes Brain Behav. 2013;12(4):424–437. doi:10.1111/gbb.12029.
  • Kempermann G, Kuhn HG, Gage FH. Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc Natl Acad Sci U S A. 1997;94(19):10409–10414. doi:10.1073/pnas.94.19.10409.
  • Hitzemann R, et al. Detection of reciprocal quantitative trait loci for acute ethanol withdrawal and ethanol consumption in heterogeneous stock mice. Psychopharmacol (Berl). 2018;10(1):1–13. doi:10.1007/s00213-008-1418-y.
  • Chesler EJ. Out of the bottleneck: the Diversity Outcross and Collaborative Cross mouse populations in behavioral genetics research. Mamm Genome. 2014;25(1–2):3–11. doi:10.1007/s00335-013-9492-9.
  • Verghese PB, Castellano JM, Holtzman DM. Apolipoprotein E in Alzheimer’s disease and other neurological disorders. Lancet Neurol. 2011;10(3):241–252. doi:10.1016/S1474-4422(10)70325-2.
  • Higuchi Y, Nelson GA, Vazquez M, Laskowitz DT, Slater JM, Pearlstein RD. Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation. JRR. 2002;43(S):S219–S224. doi:10.1269/jrr.43.S219.
  • Yeiser LA, Villasana LE, Raber J. ApoE isoform modulates effects of cranial 56Fe irradiation on spatial learning and memory in the water maze. Behav Brain Res. 2013;237:207–214. doi:10.1016/j.bbr.2012.09.029.
  • Haley GE, Villasana L, Dayger C, Davis MJ, Raber J. Apolipoprotein e genotype-dependent paradoxical short-term effects of 56Fe irradiation on the brain. Int J Radiat Oncol Biol Phys. 2012;84(3):793–799. doi:10.1016/j.ijrobp.2011.12.049.
  • Bellone JA, Gifford PS, Nishiyama NC, Hartman RE, Mao XW. Long-term effects of simulated microgravity and/or chronic exposure to low-dose gamma radiation on behavior and blood–brain barrier integrity. npj Microgravity. 2016;2(1):16019. doi:10.1038/npjmgrav.2016.19.
  • Mao XW, Nishiyama NC, Byrum SD, et al. Spaceflight induces oxidative damage to blood-brain barrier integrity in a mouse model. FASEB J. 2020;34(11):15516–15530. doi:10.1096/fj.202001754R.
  • Mao XW, Favre CJ, Fike JR, et al. High-LET radiation-induced response of microvessels in the hippocampus. Radiat Res. 2010;173(4):486–493. doi:10.1667/RR1728.1.
  • Newton SS, Fournier NM, Duman RS. Vascular growth factors in neuropsychiatry. Cell Mol Life Sci. 2013;70(10):1739–1752. doi:10.1007/s00018-013-1281-9.
  • Katus HA. Development of the cardiac troponin T immunoassay. Clin Chem. 2008;54(9):1576–1577. doi:10.1373/clinchem.2008.104810.
  • Lowe XR, Wyrobek AJ. Characterization of the early CNS stress biomarkers and profiles associated with neuropsychiatric diseases. Curr Genomics 2012;13(6):489–497.
  • Lowe XR, Marchetti F, Lu X, Wyrobek AJ. Molecular stress response in the CNS of mice after systemic exposure to interferon-alpha, ionizing radiation and ketamine. Neurotoxicology. 2009;30(2):261–268. doi:10.1016/j.neuro.2008.12.012.
  • Coleman MA, Sasi SP, Onufrak J, et al. Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2015;309(11):H1947–H1963. doi:10.1152/ajpheart.00050.2015.
  • Kiffer F, Boerma M, Allen A. Behavioral effects of space radiation: a comprehensive review of animal studies. Life Sci Space Res (Amst). 2019;21:1–21. doi:10.1016/j.lssr.2019.02.004.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.