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Title: Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain

Abstract

Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles ({epsilon}2, {epsilon}3, and {epsilon}4) 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 {sup 56}Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after {sup 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: Themore » short-term effects of {sup 56}Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.« less

Authors:
 [1];  [2]; ; ;  [1];  [1];  [2];  [2]
  1. Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
22149600
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 84; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; FLUORESCENCE; GENOTYPE; HEALTH HAZARDS; HIPPOCAMPUS; IRON 56; IRRADIATION; MICE; NERVOUS SYSTEM DISEASES; PERFORMANCE; RETENTION; SUPEROXIDE DISMUTASE; WATER

Citation Formats

Haley, Gwendolen E., Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, Villasana, Laura, Dayger, Catherine, Davis, Matthew J., Raber, Jacob, E-mail: raberj@ohsu.edu, Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, and Department of Neurology, Oregon Health and Science University, Portland, OR. Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2011.12.049.
Haley, Gwendolen E., Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, Villasana, Laura, Dayger, Catherine, Davis, Matthew J., Raber, Jacob, E-mail: raberj@ohsu.edu, Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, & Department of Neurology, Oregon Health and Science University, Portland, OR. Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain. United States. doi:10.1016/J.IJROBP.2011.12.049.
Haley, Gwendolen E., Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, Villasana, Laura, Dayger, Catherine, Davis, Matthew J., Raber, Jacob, E-mail: raberj@ohsu.edu, Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, and Department of Neurology, Oregon Health and Science University, Portland, OR. Thu . "Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain". United States. doi:10.1016/J.IJROBP.2011.12.049.
@article{osti_22149600,
title = {Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain},
author = {Haley, Gwendolen E. and Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR and Villasana, Laura and Dayger, Catherine and Davis, Matthew J. and Raber, Jacob, E-mail: raberj@ohsu.edu and Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR and Department of Neurology, Oregon Health and Science University, Portland, OR},
abstractNote = {Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles ({epsilon}2, {epsilon}3, and {epsilon}4) 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 {sup 56}Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after {sup 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 {sup 56}Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.},
doi = {10.1016/J.IJROBP.2011.12.049},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 3,
volume = 84,
place = {United States},
year = {2012},
month = {11}
}