DOI: 10.5061/dryad.0008d
title: Data from: Low-dose proton radiation effects in a transgenic mouse model of Alzheimer's Disease - implications for space travel

description: Space radiation represents a significant health risk for astronauts.
 Ground-based animal studies indicate that space radiation affects neuronal
 functions such as excitability, synaptic transmission, and plasticity, and
 it may accelerate the onset of Alzheimer's disease (AD). Although
 protons represent the main constituent in the space radiation spectrum,
 their effects on AD-related pathology have not been tested. We irradiated
 3 month-old APP/PSEN1 transgenic (TG) and wild type (WT) mice with protons
 (150 MeV; 0.1-1.0 Gy; whole body) and evaluated functional and biochemical
 hallmarks of AD. We performed behavioral tests in the water maze (WM)
 before irradiation and in the WM and Barnes maze at 3 and 6 months
 post-irradiation to evaluate spatial learning and memory. We also
 performed electrophysiological recordings in vitro in hippocampal slices
 prepared 6 and 9 months post-irradiation to evaluate excitatory synaptic
 transmission and plasticity. Next, we evaluated amyloid β (Aβ) deposition
 in the contralateral hippocampus and adjacent cortex using
 immunohistochemistry. In cortical homogenates, we analyzed the levels of
 the presynaptic marker synaptophysin by Western blotting and measured
 pro-inflammatory cytokine levels (TNFα, IL-1β, IL-6, CXCL10 and CCL2) by
 bead-based multiplex assay. TG mice performed significantly worse than WT
 mice in the WM. Irradiation of TG mice did not affect their behavioral
 performance, but reduced the amplitudes of population spikes and inhibited
 paired-pulse facilitation in CA1 neurons. These electrophysiological
 alterations in the TG mice were qualitatively different from those
 observed in WT mice, in which irradiation increased excitability and
 synaptic efficacy. Irradiation increased Aβ deposition in the cortex of TG
 mice without affecting cytokine levels and increased synaptophysin
 expression in WT mice (but not in the TG mice). Although irradiation with
 protons increased Aβ deposition, the complex functional and biochemical
 results indicate that irradiation effects are not synergistic to AD
 pathology.
description: Fig 2 WM swim distance
 raw dataSwim Distance in Water
 Maze in APP/PS1 TG and WT mice irradiated with protons measured pre-, 3
 and 6 months postirradiationFig 3 and S3Fig Input
 Output Curves at Max and Full Stimualtion intesitiesI-O functions in CA1
 neurons in slices from TG and WT mice 9 months
 post-irradiation.Fig 3 and S3Fig Input Output
 Curves at Max and Full.xlsxFig 4 Paired-Pulse
 Facilitation in TG and WT mice at 9 monthsPPF in CA1 neurons of TG
 and WT mice 9 months post-irradiation. PPF ratios are shown at all tested
 inter-stimulus intervals (ISI) of 20-400 ms.Fig 5 Paired-Pulse
 Facilitation in TG at 6 and 9 monthsRadiation effects on
 age-related increase of PPF in TG mice. Comparison of PPF between at 6 and
 9 months in TG mice revealed significant interaction between radiation
 dose and post-irradiation time point with enhanced PPF in 9-month TG
 control group only. Note that the graph indicates PPF values acquired at
 20 ms only (strongest PPF effect); however, the statistical model included
 PPF recorded at all ISIs.Fig 6 Paired-Pulse
 Inhibition of PS in TG and WT mice at 9 monthsAlthough the bar graph
 indicates PPI values acquired at 6 ms; the statistical model included PPI
 recorded at all ISIsFig 7. IHC analyses of
 Abeta deposits in TG mice 9 months post-irradiationImmunohistochemical
 analyses of Abeta deposition analyses of Aβ deposits in TG APP/PS1 mice 9
 months post-irradiation.Fig 8. WB analyses of
 synaptophysin in the cortex of TG and WT mice at 9
 monthsWestern Blot analyses of
 synaptophysin in the cortex of TG and WT mice 9 months
 post-irradiation.Fig 9. Cytokine levels
 in the cortex of TG and WT mice 9 months
 post-irradiation.Luminex analyses of
 cytokine levels in the cortex of TG and WT mice 9 months
 post-irradiation.