Abstract
Many studies have shown that imbalance of mineral metabolism may play an important role in Alzheimer’s disease (AD) progression. It was recently reported that selenium could reverse memory deficits in AD mouse model. We carried out multi-time-point ionome analysis to investigate the interactions among 15 elements in the brain by using a triple-transgenic mouse model of AD with/without high-dose sodium selenate supplementation. Except selenium, the majority of significantly changed elements showed a reduced level after 6-month selenate supplementation, especially iron whose levels were completely reversed to normal state at almost all examined time points. We then built the elemental correlation network for each time point. Significant and specific elemental correlations and correlation changes were identified, implying a highly complex and dynamic crosstalk between selenium and other elements during long-term supplementation with selenate. Finally, we measured the activities of two important anti-oxidative selenoenzymes, glutathione peroxidase and thioredoxin reductase, and found that they were remarkably increased in the cerebrum of selenate-treated mice, suggesting that selenoenzyme-mediated protection against oxidative stress might also be involved in the therapeutic effect of selenate in AD. Overall, this study should contribute to our understanding of the mechanism related to the potential use of selenate in AD treatment.
Highlights
Many studies have shown that imbalance of mineral metabolism may play an important role in Alzheimer’s disease (AD) progression
Metal dyshomeostasis is frequently observed in AD patients due to anomalous binding of metals such as iron (Fe), copper (Cu) and zinc (Zn), or impaired regulation of redox-active metals which can induce the formation of reactive oxygen species (ROS) and neuronal damage[12,13,14,15,16]
In spite that some metal chelators could decrease the concentration of certain metals to some extent in the brains of AD mouse models or patients, they may interfere with the normal metabolism of other metals and disrupt the whole mineral metabolic network
Summary
Many studies have shown that imbalance of mineral metabolism may play an important role in Alzheimer’s disease (AD) progression. Metal dyshomeostasis is frequently observed in AD patients due to anomalous binding of metals such as iron (Fe), copper (Cu) and zinc (Zn), or impaired regulation of redox-active metals which can induce the formation of reactive oxygen species (ROS) and neuronal damage[12,13,14,15,16] Targeting some of these metals might be an alternative approach to treat this disease[17]. Researchers found that high-dose dietary supplementation of selenite could reduce the amount of senile APs in the brain using Tg2576 transgenic mice[31] Another Se form, selenate, has aroused researchers’ interest due to its lower physical toxicity and outstanding performance in reducing tau hyperphosphorylation, which may become a promising novel therapeutic drug in AD32–34. As the major metalloid micronutrient, the interaction between Se and other metals or minerals is not clear yet
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