Undergraduate Program in Biology, Vanderbilt University, Nashville, TN 37232, USA.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Nutrients. 2018 Jul 9;10(7):883. doi: 10.3390/nu10070883.
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.
本研究强调了在死后 24 小时内,小鼠大脑中发生的几种氧化应激和抗氧化状态测量的变化。在短短 2 小时内,皮质中的抗坏血酸(维生素 C)和谷胱甘肽含量显著下降,丙二醛水平升高。直到 24 小时,还观察到了从基线开始的进一步变化,包括羰基和巯基的形成。与野生型或 5XFAD 小鼠相比,开始时抗坏血酸水平较低的(gulo 小鼠)大脑中观察到的变化最大。在相同条件下还对来自 9 例阿尔茨海默病病例和 5 例对照的皮质样本进行了检测。死后间隔时间从 6 小时到 47 小时不等,所有样本在测量时的抗坏血酸水平都较低。丙二醛水平在阿尔茨海默病病例中较低。尽管抗坏血酸和谷胱甘肽水平之间存在强烈的正相关,但未观察到其他氧化应激测量或死后间隔之间的相关性。这些数据表明,死亡后最初几小时内发生的分子变化可能掩盖了患者组之间的差异。在对人体脑组织进行研究时,必须谨慎对待,因为不知道生前的营养状况,以避免结果出现偏差或混淆。