Data from: Low-dose proton radiation effects in a transgenic mouse model of Alzheimer's Disease - implications for space travel

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.