Abstract
The current study highlighted several changes in measures of oxidative stress and antioxidant status that take place in the mouse brain over the course of 24 h post-mortem. Ascorbic acid (vitamin C) and glutathione both decreased significantly in cortex in as little as 2 h and malondialdehyde levels increased. Further change from baseline was observed up to 24 h, including carbonyl and sulfhydryl formation. The greatest changes were observed in brains that began with low ascorbic acid levels (gulo−/− mice) compared to wild-type or 5XFAD mice. Cortical samples from nine Alzheimer’s Disease cases and five controls were also assayed under the same conditions. Post mortem intervals ranged from 6 to 47 h and all samples had low ascorbic acid levels at time of measurement. Malondialdehyde levels were lower in Alzheimer’s Disease cases. Despite a strong positive correlation between ascorbic acid and glutathione levels, no other correlations among oxidative stress measures or post mortem interval were observed. Together the data suggest that molecular changes occurring within the first hours of death may mask differences between patient groups. Care must be taken interpreting studies in human brain tissue where ante-mortem nutrient status is not known to avoid bias or confounding of results.
Highlights
Oxidative stress has long been a major focus of research in neurodegenerative diseases and in Alzheimer’s Disease in particular [1]
To address the extent to which post-mortem interval (PMI) may determine changes in oxidative stress status we studied a range of markers of antioxidant status in brain in mice under low ascorbic acid dietary supplementation and mice carrying mutations derived from familial Alzheimer’s
We clearly show that ante-mortem ascorbic acid level is a critical determinant of overall oxidative stress in the gulo−/− mice that, like humans, are dependent on dietary intake
Summary
Oxidative stress has long been a major focus of research in neurodegenerative diseases and in Alzheimer’s Disease in particular [1]. Some increased markers of oxidative stress have been detected through post-mortem study in Alzheimer’s. It was concluded that the evidence from this meta-analysis was insufficient to support the general theory of a major change across oxidative stress processes in Alzheimer’s Disease. Several measures of oxidative stress can be assessed in blood without any complications from processing time and these markers have previously been researched as a possible diagnostic tool in Alzheimer’s Disease [12]. To address the extent to which PMI may determine changes in oxidative stress status we studied a range of markers of antioxidant status in brain in mice under low ascorbic acid (vitamin C) dietary supplementation (gulo−/− mice) and mice carrying mutations derived from familial Alzheimer’s. We included many of the measures typically used and reported in clinical research studies including ascorbic acid, total glutathione, malondialdehyde, protein carbonylation and sulfhydryl groups
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