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Restoration of Cognitive Performance in Mice Carrying a Deficient Allele of 8-Oxoguanine DNA Glycosylase by X-ray Irradiation

Abstract

Environmental stressors inducing oxidative stress such as ionizing radiation may influence cognitive function and neuronal plasticity. Recent studies have shown that transgenic mice deficient of DNA glycosylases display unexpected cognitive deficiencies related to changes in gene expression in the hippocampus. The main objectives of the present study were to determine learning and memory performance in C57BL/6NTac 8-oxoguanine DNA glycosylase 1 (Ogg1)+/− (heterozygote) and Ogg1+/+ (wild type, WT) mice, to study whether a single acute X-ray challenge (0.5 Gy, dose rate 0.457 Gy/min) influenced the cognitive performance in the Barnes maze, and if such differences were related to changes in gene expression levels in the hippocampus. We found that the Ogg1+/− mice exhibited poorer early-phase learning performance compared to the WT mice. Surprisingly, X-ray exposure of the Ogg1+/− animals improved their early-phase learning performance. No persistent effects on memory in the late-phase (6 weeks after irradiation) were observed. Our results further suggest that expression of 3 (Adrb1, Il1b, Prdx6) out of in total 35 genes investigated in the Ogg1+/− hippocampus is correlated to spatial learning in the Barnes maze.

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Acknowledgments

Thanks to Kari G. Løken at NIPH’s animal facility, Karin E. Zimmer and Alexandra M. Hudecova (Norwegian University of Life Sciences) for excellent support on the Barnes maze studies, and Arip Ikhsani for technical support.

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Correspondence to Oddvar Myhre.

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The authors declare that they have no conflict of interest.

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All applicable national and institutional guidelines for the care and use of animals were followed. All procedures performed in the studies involving animals were in accordance with the ethical standards at the NIPH. The animal study permit was FOTS ID 8033.

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Hofer, T., Duale, N., Muusse, M. et al. Restoration of Cognitive Performance in Mice Carrying a Deficient Allele of 8-Oxoguanine DNA Glycosylase by X-ray Irradiation. Neurotox Res 33, 824–836 (2018). https://doi.org/10.1007/s12640-017-9833-7

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Keywords

  • adrenergic receptor
  • behavior
  • brain
  • interleukin
  • knockout
  • peroxiredoxin