title: Apolipoprotein e genotype-dependent paradoxical short-term effects of (56)fe irradiation on the brain.
abstract: OBJECTIVE
  In humans, apolipoprotein E (apoE) is encoded by three major alleles (ε2, ε3, and ε4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of (56)Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk.
  
  
  METHODS
  We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after (56)Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, we assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis.
  
  
  RESULTS
  In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice.
  
  
  CONCLUSIONS
  The short-term effects of (56)Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Gwendolen E
authors.initials: GE
authors.lastname: Haley
authors.forename: Laura
authors.initials: L
authors.lastname: Villasana
authors.forename: Catherine
authors.initials: C
authors.lastname: Dayger
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Davis
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
mesh_terms: D000818:Animals; D053329:Apolipoprotein E2 / Q000235:genetics; D053318:Apolipoprotein E3 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D015153:Blotting, Western; D018891:Dentate Gyrus / Q000378:metabolism / Q000528:radiation effects; D004996:Ethidium / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000528:radiation effects; D008569:Memory Disorders / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; C067883:dihydroethidium; C002744:3-nitrotyrosine; D014443:Tyrosine; D007501:Iron; D013482:Superoxide Dismutase; D004996:Ethidium