Data from: Low-dose proton radiation effects in a transgenic mouse model of Alzheimer's Disease - implications for space travel
Data files
Oct 02, 2018 version files 193.43 KB
-
Fig 2 WM swim distance raw data.xlsx
20.77 KB
-
Fig 3 and S3Fig Input Output Curves at Max and Full.xlsx
101.53 KB
-
Fig 4 Paired-Pulse Facilitation in TG and WT mice at 9 months.xlsx
12.05 KB
-
Fig 5 Paired-Pulse Facilitation in TG at 6 and 9 months.xlsx
10.08 KB
-
Fig 6 Paired-Pulse Inhibition of PS in TG and WT mice at 9 months.xlsx
12.46 KB
-
Fig 7. IHC analyses of Abeta deposits in TG mice 9 months post-irradiation.xlsx
10.63 KB
-
Fig 8. WB analyses of synaptophysin in the cortex of TG and WT mice at 9 months .xlsx
8.64 KB
-
Fig 9. Cytokine levels in the cortex of TG and WT mice 9 months post-irradiation. .xlsx
17.27 KB
Abstract
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.