Irradiation enhances hippocampus-dependent cognition in mice deficient in extracellular superoxide dismutase.
The effects of ionizing irradiation on the brain are associated with oxidative stress. While oxidative stress following irradiation is generally viewed as detrimental for hippocampal function, it might have beneficial effects as part of an adaptive or preconditioning response to a subsequent challenge. Here we show that in contrast to what is seen in wild-type mice, irradiation enhances hippocampus- dependent cognitive measures in mice lacking extracellular superoxide dismutase. These outcomes were associated with genotype-dependent effects on measures of oxidative stress. When cortices and hippocampi were analyzed for nitrotyrosine formation as an index of oxidative stress, the levels were chronically elevated in mice lacking extracellular superoxide dismutase. However, irradiation caused a greater increase in nitrotyrosine levels in wild-type mice than mice lacking extracellular superoxide dismutase. These paradoxical genotype-dependent effects of irradiation on measures of oxidative stress and cognitive function underscore potential beneficial effects associated with chronic oxidative stress if it exists prior to a secondary insult such as irradiation.
Raber
Jacob
J
Department of Behavioral Neuroscience, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. raberj@ohsu.edu
Villasana
Laura
L
Rosenberg
Jenna
J
Zou
Yani
Y
Huang
Ting Ting
TT
Fike
John R
JR
D000818:Animals; D015153:Blotting, Western; D003071:Cognition / Q000502:physiology*; D045604:Extracellular Fluid; D006624:Hippocampus / Q000201:enzymology / Q000528:radiation effects*; D008297:Male; D018782:Maze Learning / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000172:deficiency / Q000378:metabolism*
D055748:SOXB1 Transcription Factors; C527786:Sox3 protein, mouse