Effects of hyperoxia in alzheimers transgenic mice
An association between major surgery in the elderly and precipitation of Alzheimers disease (AD) has been reported. Hyperoxia (100%) oxygen is commonly administered after surgery to increase the oxygen content of blood. However, hyperoxia is a potent cerebral vasoconstrictor and generator of free ra...
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| Format: | Others |
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Scholar Commons
2005
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| Online Access: | http://scholarcommons.usf.edu/etd/2836 http://scholarcommons.usf.edu/cgi/viewcontent.cgi?article=3835&context=etd |
| Summary: | An association between major surgery in the elderly and precipitation of Alzheimers disease (AD) has been reported. Hyperoxia (100%) oxygen is commonly administered after surgery to increase the oxygen content of blood. However, hyperoxia is a potent cerebral vasoconstrictor and generator of free radicals, as is [beta]amyloid (A[beta];). This study was aimed at examining behavioral, neuropathological, and neurochemical effects of hyperoxia treatments in APPsw transgenic mice (Tg+), which have elevated brain A[beta]; levels by 3-4 months of age but are not yet cognitively-impaired. At 3 months of age, Tg+ mice were pre-tested in the radial arm water maze (RAWM) task of working memory and found to be unimpaired. At 4.5 months of age, half of the Tg+ mice received the first of 3 equally-spaced hyperoxia sessions (3 hrs each) given over the ensuing 3 months. The other half of the Tg+ mice were exposed to compressed air during these 3 sessions.
RAWM testing performed immediately following the final gas session at 7.5 months of age revealed significant working memory impairment in Tg+ mice exposed to hyperoxia. The Tg+ group that was exposed to placebo treatment showed a trend towards impairment, however, was not significantly different from the non-transgenic group. Hyperoxia-induced memory impairment in Tg+ mice did not involve changes in brain A[beta] deposition, degenerative cell numbers in hippocampus, neocortical lipid peroxidation, or hippocampal levels of APP, ApoE, COX-2, or GFAP. The combination of excess A[beta] and hyperoxia could have induced greater oxidative stress and cerebral vasoconstriction than either one alone, resulting in a pathologic cerebral hypoperfusion that triggered subsequent cognitive impairment. |
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