Oxidative Stress Levels in the Brain Are Determined by Post-Mortem Interval and Ante-Mortem Vitamin C State but Not Alzheimer’s Disease Status

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.

Polyunsaturated Fatty Acid Composition of Cerebrospinal Fluid Fractions Shows Their Contribution to Cognitive Resilience of a Pre-symptomatic Alzheimer’s Disease Cohort

“…AA metabolites are associated with cellular redox increase of Cox-2 expression, while n-3 PUFA decreases Cox-2 expression (Gravaghi et al, 2011;Mitjavila and Moreno, 2012). Several studies have documented increased oxidative stress in AD brain (Butterfield et al, 1999;Ansari and Scheff, 2010;Bonda et al, 2010;Mosconi et al, 2008;Raukas et al, 2012;Lee et al, 2013;Eckman et al, 2018) typified by increases in reactive oxygen species (ROS). ROS contribute to neurodegeneration and atrophy in neurites (Munnamalai and Suter, 2009).…”

Distribution Pattern of Closed and Extended Forms of Glutathione in the Human Brain: MR Spectroscopic Study

“…Post-mortem studies have mitigated challenges faced in directly measuring levels of proteins or metabolites from healthy or disease populations like sample tissue collection from live patients. 31 Studying GSH levels in the autopsy brain has provided a baseline for future comparisons with GSH levels found in the same brain regions of patients suffering from neurodegenerative or neuropsychiatric conditions. One of the earliest reports indicated the concentrations of a large group of amino acids along with GSH in different brain regions.…”

Ascorbate Is a Primary Antioxidant in Mammals

“…Supplementation of the 5XFAD mice under a GULO −/− background with a higher dose of Asc reduces amyloid plaque and ameliorates integrity of the blood–brain barrier and mitochondrial morphology. A later study using these mice also showed that the Asc status, but not Alzheimer’s disease status, was correlated with oxidative stress in the brain [ 89 ].…”