Effects of photon irradiation in the presence and absence of hindlimb unloading on the behavioral performance and metabolic pathways in the plasma of Fischer rats

Jacob Raber, Sarah Holden, Kat Kessler, Breanna Glaeser, Chloe McQuesten, Mitali Chaudhari, Fiona Stenzel, Marek Lenarczyk, Scott Willem Leonard, Jeffrey Morré, Jaewoo Choi, Amy Kronenberg, Alexander Borg, Andy Kwok, Jan Frederik Stevens, Christopher Olsen, Jeffrey S. Willey, Gerd Bobe, Jessica Minnier, John E. Baker

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: The space environment astronauts experience during space missions consists of multiple environmental challenges, including microgravity. In this study, we assessed the behavioral and cognitive performances of male Fisher rats 2 months after sham irradiation or total body irradiation with photons in the absence or presence of simulated microgravity. We analyzed the plasma collected 9 months after sham irradiation or total body irradiation for distinct alterations in metabolic pathways and to determine whether changes to metabolic measures were associated with specific behavioral and cognitive measures. Methods: A total of 344 male Fischer rats were irradiated with photons (6 MeV; 3, 8, or 10 Gy) in the absence or presence of simulated weightlessness achieved using hindlimb unloading (HU). To identify potential plasma biomarkers of photon radiation exposure or the HU condition for behavioral or cognitive performance, we performed regression analyses. Results: The behavioral effects of HU on activity levels in an open field, measures of anxiety in an elevated plus maze, and anhedonia in the M&M consumption test were more pronounced than those of photon irradiation. Phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism and biosynthesis showed very strong pathway changes, following photon irradiation and HU in animals irradiated with 3 Gy. Here, 29 out of 101 plasma metabolites were associated with 1 out of 13 behavioral measures. In the absence of HU, 22 metabolites were related to behavioral and cognitive measures. In HU animals that were sham-irradiated or irradiated with 8 Gy, one metabolite was related to behavioral and cognitive measures. In HU animals irradiated with 3 Gy, six metabolites were related to behavioral and cognitive measures. Discussion: These data suggest that it will be possible to develop stable plasma biomarkers of behavioral and cognitive performance, following environmental challenges like HU and radiation exposure.

Original languageEnglish (US)
Article number1316186
JournalFrontiers in Physiology
Volume14
DOIs
StatePublished - 2023

Keywords

  • Fischer
  • anhedonia
  • elevated plus maze
  • hindlimb unloading
  • metabolomics
  • open field
  • photon irradiation
  • rats

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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