Effects of 5-Ion Beam Irradiation and Hindlimb Unloading on Metabolic Pathways in Plasma and Brain of Behaviorally Tested WAG/Rij Rats

Jacob Raber, Sarah Holden, Reetesh Sudhakar, Reed Hall, Breanna Glaeser, Marek Lenarczyk, Kristen Rockwell, Natalie Nawarawong, Jennifer Sterrett, Ruby Perez, Scott William Leonard, Jeffrey Morré, Jaewoo Choi, Amy Kronenberg, Alexander Borg, Andy Kwok, Jan Frederik Stevens, Christopher M. Olsen, Jeffrey S. Willey, Gerd BobeJohn Baker

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


A limitation of simulated space radiation studies is that radiation exposure is not the only environmental challenge astronauts face during missions. Therefore, we characterized behavioral and cognitive performance of male WAG/Rij rats 3 months after sham-irradiation or total body irradiation with a simplified 5-ion mixed beam exposure in the absence or presence of simulated weightlessness using hindlimb unloading (HU) alone. Six months following behavioral and cognitive testing or 9 months following sham-irradiation or total body irradiation, plasma and brain tissues (hippocampus and cortex) were processed to determine whether the behavioral and cognitive effects were associated with long-term alterations in metabolic pathways in plasma and brain. Sham HU, but not irradiated HU, rats were impaired in spatial habituation learning. Rats irradiated with 1.5 Gy showed increased depressive-like behaviors. This was seen in the absence but not presence of HU. Thus, HU has differential effects in sham-irradiated and irradiated animals and specific behavioral measures are associated with plasma levels of distinct metabolites 6 months later. The combined effects of HU and radiation on metabolic pathways in plasma and brain illustrate the complex interaction of environmental stressors and highlights the importance of assessing these interactions.

Original languageEnglish (US)
Article number746509
JournalFrontiers in Physiology
StatePublished - Sep 27 2021


  • WAG/Rij/Cmcr
  • forced swim test
  • hindlimb unloading
  • metabolomics
  • open field
  • rats
  • simplified GCR simulation
  • space radiation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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