Long-term behavioral effects of mixed-ion irradiation on wild type C57BL6/J and Alzheimer's-like APPswe/PS1dE9 mice

Maren Schroeder, B.A.
Department of Neurology
Division of Basic Neuroscience Research
Poster Overview

As human spaceflight becomes increasingly achievable, it is important to study the effects of space radiation on humans. Central Nervous System tissues have traditionally been considered to be resistant to space radiation, though recent studies have challenged this. Moreover, many neurological diseases develop years before symptoms occur, so space radiation may accelerate pathologies in otherwise cognitively healthy astronauts. To that end, we studied the effects of space-like radiation (GCRsim) and gamma irradiation from Brookhaven National Laboratory (Upton, NY) on male and female, wildtype (WT) and Alzheimer’s disease-like (APP/PS1dE9) mice. The latter have mutations resulting in amyloid plaques and cognitive deficits. Mice received either sham, 0.5 Gy, or 0.75 Gy GCRsim or 0.75 Gy or 2 Gy of gamma irradiation and underwent behavioral testing 8 months later. The behavioral tests measure locomotor activity, grip strength, endurance, motor learning, anxiety- and depressive-like behavior, spatial and fear memory, and sensorimotor gaiting. While combined analyses for the two cohorts are underway, to date we have seen that WT males that received 0.75 Gy GCRsim and 2 Gy gamma irradiation showed impaired spatial memory. This supports previous findings that space-like radiation may have long-lasting deleterious cognitive effects, particularly in male mice.

Scientific Abstract

Space radiation exposure to high charge and energy particles in deep space may pose CNS risks to humans including exacerbating predisposition to neurological diseases. Previously, we found that male wildtype (WT) and Alzheimer’s disease-like APP/PS1dE9 mice showed cognitive deficits 8 months after 56Fe irradiation. Presently, we investigated the long-term effects of Brookhaven National Laboratory’s Galactic Cosmic Radiation mixed-field beam (GCRsim: protons, 56Fe, 16O, 28Si, and 4He) on behavior. A total of 228 four month-old male and female, WT and APP/PS1dE9 mice were divided into 2 cohorts and received sham, 0.5 Gy or 0.75 Gy GCRsim, or 0.75 Gy or 2 Gy gamma radiation. Eight months later, a subset of mice (n=124) were tested for changes in motor function (Open Field, Grip Strength, Wire Hang, Rotarod), anxiety (Elevated Plus Maze), cognition [Spatial Novelty Y Maze (SNYM), Contextual Fear Conditioning], depression (Tail Suspension), and sensorimotor gaiting (Startle, Pre-Pulse Inhibition). WT male 0.75 Gy GCRsim and gamma 2 Gy mice showed cognitive impairment on the SNYM. Radiation had no effect on locomotion in the Open Field. Further analyses are underway. So far, our results suggest that GCRsim may worsen spatial memory in WT male mice, consistent with our previous findings with 56Fe irradiation.

Clinical Implications
This research is relevant to the cognitive health of astronauts and cancer patients undergoing gamma radiation, particularly those at risk for Alzheimer’s disease. Our findings suggest that cognitive impairment, particularly in males, may result from these treatments, meriting further investigation.
Research Areas
Authors
Maren K. Schroeder, Khyrul A. Khan, Barbara J. Caldarone PhD, Cynthia A. Lemere PhD
Principal Investigator
Cynthia Lemere, PhD

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