title: Exposure to 56Fe-particle radiation accelerates electrophysiological alterations in the hippocampus of APP23 transgenic mice.
abstract: Abstract An unavoidable complication of space travel is exposure to high-charge, high-energy (HZE) particles. In animal studies, exposure of the CNS to HZE-particle radiation leads to neurological alterations similar to those seen in aging or Alzheimer's disease. In this study we examined whether HZE-particle radiation accelerated the age-related neuronal dysfunction that was previously described in transgenic mice overexpressing human amyloid precursor protein (APP). These APP23 transgenic mice exhibit age-related behavioral abnormalities and deficits in synaptic transmission. We exposed 7-week-old APP23 transgenic males to brain-only (56)Fe-particle radiation (600 MeV/nucleon; 1, 2, 4 Gy) and recorded synaptic transmission in hippocampal slices at 2, 6, 9, 14 and 18-24 months. We stimulated Schaeffer collaterals and recorded field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) in CA1 neurons. Radiation accelerated the onset of age-related fEPSP decrements recorded at the PS threshold from 14 months of age to 9 months and reduced synaptic efficacy. At 9 months, radiation also reduced PS amplitudes. At 6 months, we observed a temporary deficit in paired-pulse inhibition of the PS at 2 Gy. Radiation did not significantly affect survival of APP23 transgenic mice. We conclude that irradiation of the brain with HZE particles accelerates Alzheimer's disease-related neurological deficits.
authors.affiliation: Department of Radiation Medicine, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA. rvlkolinsky@dominion.llumc.edu
authors.forename: R
authors.initials: R
authors.lastname: Vlkolinsky
authors.forename: E
authors.initials: E
authors.lastname: Titova
authors.forename: T
authors.initials: T
authors.lastname: Krucker
authors.forename: B B
authors.initials: BB
authors.lastname: Chi
authors.forename: M
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: G A
authors.initials: GA
authors.lastname: Nelson
authors.forename: A
authors.initials: A
authors.lastname: Obenaus
mesh_terms: D000818:Animals; D055724:Electrophysiological Phenomena / Q000528:radiation effects*; D019706:Excitatory Postsynaptic Potentials / Q000528:radiation effects; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology* / Q000528:radiation effects*; D006801:Humans; D007501:Iron / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D011839:Radiation, Ionizing; D016019:Survival Analysis; D013569:Synapses / Q000502:physiology / Q000528:radiation effects
chemical_list: D007501:Iron