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

Raber, Jacob; Holden, Sarah; Sudhakar, Reetesh; Hall, Reed; Glaeser, Breanna; Lenarczyk, Marek; Rockwell, Kristen; Nawarawong, Natalie N.; Sterrett, Jennifer; Perez, Ruby; Leonard, Scott W.; Morré, Jeff; Choi, Jaewoo; Kronenberg, Amy; Borg, Alexander M; Kwok, Andy; Stevens, Jeffrey S.; Olsen, Christopher M.; Willey, Jeffrey S.; Bobe, Gerd; Baker, John E.

doi:10.3389/fphys.2021.746509

Cited by 15 publications

(18 citation statements)

References 51 publications

(63 reference statements)

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“…While there are multiple possible explanations for these differential effects, at this time these are largely speculative due to the lack of data on the ion/LET dependency. Only eight published studies [4,[15][16][42][43][44][45][46] currently exist on the impact of multi-ion GCR exposure that mostly assess cognitive function. Aside from the present work, one study has directly compared this multi-ion spectrum to a single ion in a touchscreen associative recognition memory task where rats exposed to GCRsim exhibited greater deficits when presented with changes in multiple stimuli at once relative to 4 He rats [4].…”

Section: Discussionmentioning

confidence: 99%

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Rapid loss of fine motor skills after low dose space radiation exposure

Blackwell

Fesshaye²,

Tidmore³

et al. 2022

Behavioural Brain Research

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Section: Discussionmentioning

confidence: 99%

“…The relative dose contribution of the 6-ion GCRSim beam is 74% protons, 18% 4 He, 6% 16 Oxygen, 1% 28 Silicon (Si), and 1% 56 Iron [11]. Only a handful of studies have been conducted to evaluate the effects of GCRsim on cognition [12][13][14][15][16], and none of this work has characterized sensorimotor function.…”

Section: Introductionmentioning

confidence: 99%

Rapid loss of fine motor skills after low dose space radiation exposure

Blackwell

Fesshaye²,

Tidmore³

et al. 2022

Behavioural Brain Research

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“…Recent experiments suggest effects of HU and 5 ion GCRsim compete in male rats. Sham HU animals were impaired in spatial habituation learning, but GCRsim + HU rats were not [27].…”

Section: Introductionmentioning

confidence: 84%

Combined space stressors induce independent behavioral deficits predicted by early peripheral blood monocytes

Rienecker

Grue

Paladini

et al. 2022

Preprint

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Interplanetary space travel poses many hazards to the human body. To protect astronaut health and performance on critical missions, there is first a need to understand the effects of deep space hazards, including ionizing radiation, confinement, and altered gravity. Previous studies of rodents exposed to a single such stressor document significant deficits, but our study is the first to investigate possible cumulative and synergistic impacts of simultaneous ionizing radiation, confinement, and altered gravity on behavior and cognition. Our cohort was divided between 6-month-old female and male mice in group, social isolation, or hindlimb unloading housing, exposed to 0 or 50 cGy of 5 ion simplified simulated Galactic Cosmic Radiation (GCRsim). We report interactions and independent effects of GCRsim exposure and housing conditions on behavioral and cognitive performance. Exposure to GCRsim drove changes in immune cell populations in peripheral blood collected early after irradiation, while housing conditions drove changes in blood collected at a later point. Female mice were largely resilient to deficits observed in male mice. Finally, we used principal component analysis to represent total deficits as principal component scores, which were predicted by general linear models using GCR exposure, housing condition, and early blood biomarkers.

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“…Exploratory activity and anxiety were measured in the open field. In this task, mice were placed in enclosures (L 40.6 × W 40.6 × H 40.6 cm) for a 10-min trial on 2 consecutive days, as described 39 . Time spent in the center of the open field was analyzed to assess measures of anxiety.…”

Section: Methodsmentioning

confidence: 99%

Behavioral and cognitive performance of humanized APOEε3/ε3 liver mice in relation to plasma apolipoprotein E levels

Kessler

Giannisis

Bial

et al. 2023

Sci Rep

Self Cite

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Plasma apolipoprotein E levels were previously associated with the risk of developing Alzheimer’s disease (AD), levels of cerebrospinal fluid AD biomarkers, cognition and imaging brain measures. Outside the brain, the liver is the primary source of apoE and liver transplantation studies have demonstrated that liver-derived apoE does not cross the blood–brain-barrier. How hepatic apoE may be implicated in behavioral and cognitive performance is not clear. In the current study, we behaviorally tested FRGN mice with humanized liver harboring the ε3/ε3 genotype (E3-human liver (HL)) and compared their behavioral and cognitive performance with that of age-matched ε3/ε3 targeted replacement (E3-TR) mice, the latter produces human apoE3 throughout the body whereas the E3-HL mice endogenously produce human apoE3 only in the liver. We also compared the liver weights and plasma apoE levels, and assessed whether plasma apoE levels were correlated with behavioral or cognitive measures in both models. E3-HL were more active but performed cognitively worse than E3-TR mice. E3-HL mice moved more in the open field containing objects, showed higher activity levels in the Y maze, showed higher activity levels during the baseline period in the fear conditioning test than E3-TR mice, and swam faster than E3-TR mice during training to locate the visible platform in the water maze. However, E3-HL mice showed reduced spatial memory retention in the water maze and reduced fear learning and contextual and cued fear memory than E3-TR mice. Liver weights were greater in E3-HL than E3-TR mice and sex-dependent only in the latter model. Plasma apoE3 levels were similar to those found in humans and comparable in female and male E3-TR mice but higher in female E3-HL mice. Finally, we found correlations between plasma apoE levels and behavioral and cognitive measures which were predominantly model-dependent. Our study demonstrates mouse-model dependent associations between plasma apoE levels, behavior and cognition in an ‘AD-neutral’ setting and suggests that a humanized liver might be sufficient to induce mouse behavioral and cognitive phenotypes.

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

Cited by 15 publications

References 51 publications

Rapid loss of fine motor skills after low dose space radiation exposure

Rapid loss of fine motor skills after low dose space radiation exposure

Combined space stressors induce independent behavioral deficits predicted by early peripheral blood monocytes

Behavioral and cognitive performance of humanized APOEε3/ε3 liver mice in relation to plasma apolipoprotein E levels

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