title: Long-term effects of 56Fe irradiation on spatial memory of mice: role of sex and apolipoprotein E isoform.
abstract: OBJECTIVE
  To assess whether the effects of cranial (56)Fe irradiation on the spatial memory of mice in the water maze are sex and apolipoprotein E (apoE) isoform dependent and whether radiation-induced changes in spatial memory are associated with changes in the dendritic marker microtubule-associated protein 2 (MAP-2) and the presynaptic marker synaptophysin.
  
  
  METHODS
  Two-month-old male and female mice expressing human apoE3 or apoE4 received either a 3-Gy dose of cranial (56)Fe irradiation (600 MeV/amu) or sham irradiation. Mice were tested in a water maze task 13 months later to assess effects of irradiation on spatial memory retention. After behavioral testing, the brain tissues of these mice were analyzed for synaptophysin and MAP-2 immunoreactivity.
  
  
  RESULTS
  After irradiation, spatial memory retention of apoE3 female, but not male, mice was impaired. A general genotype deficit in spatial memory was observed in sham-irradiated apoE4 mice. Strikingly, irradiation prevented this genotype deficit in apoE4 male mice. A similar but nonsignificant trend was observed in apoE4 female mice. Although there was no change in MAP-2 immunoreactivity after irradiation, synaptophysin immunoreactivity was increased in irradiated female mice, independent of genotype.
  
  
  CONCLUSIONS
  The effects of (56)Fe irradiation on the spatial memory retention of mice are critically influenced by sex, and the direction of these effects is influenced by apoE isoform. Although in female mice synaptophysin immunoreactivity provides a sensitive marker for effects of irradiation, it cannot explain the apoE genotype-dependent effects of irradiation on the spatial memory retention of the mice.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97201, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Villasana
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Benice
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
mesh_terms: D000818:Animals; D053318:Apolipoprotein E3 / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D007501:Iron / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000502:physiology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011829:Radiation Dosage; D012153:Retention, Psychology / Q000502:physiology / Q000528:radiation effects*; D012737:Sex Factors; D016708:Synaptophysin / Q000378:metabolism*
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D015415:Biomarkers; D008869:Microtubule-Associated Proteins; D016708:Synaptophysin; D007501:Iron