Selenium Forms and Dosages Determined Their Biological Actions in Mouse Models of Parkinson’s Disease

Abstract

Selenium (Se), an essential antioxidant trace element, is reported to play a role in Parkinson’s disease (PD). However, there is a lack of systematic studies on different Se forms against PD. Our study is designed to compare the neuroprotective effects of inorganic and organic Se in two classical PD mice models and investigate the underlying mechanisms for their potentially differential actions against PD. In this study, different dosages of inorganic sodium selenite (Se-Na) or organic seleno-L-methionine (Se-Met) were fed to either acute or chronic PD mice models, and their neuroprotective effects and mechanisms were explored and compared. Se-Na provided better neuroprotective effects in PD mice than Se-Met administered at the same but at a relatively low Se dosage. Se-Na treatment could influence GPX activities but not their mRNA expressions in the midbrains of PD mice. The enhanced GPX activities caused by Se-Na, but not Se-Met, in PD mice could be the major reason for the positive actions of inorganic Se to prevent dopaminergic neuronal loss in this study. In vivo bio-distribution experiments found MPTP injection greatly changed Se bio-distribution in mice, which led to reversed alterations in the bioavailability of Se-Met and Se-Na. Se-Na had higher bioavailability than Se-Met in PD mice, which could explain its better neuroprotective effects compared to Se-Met. Our results proved that Se forms and dosages determined their biological actions in mouse models of PD. Our study will provide valuable scientific evidence to researchers and/or medical professionals in using Se for PD prevention or therapy.

Association between Parkinson disease and selenium levels in the body: A systematic review and meta-analysis

“…[45] Such findings underscore the necessity of further research to explore selenium's impact across different stages of PD, potentially unveiling stagespecific therapeutic or preventive measures. [46] This aspect aligns with our findings of elevated selenium levels in the CSF of PD patients, suggesting that selenium may play a complex role in the disease's pathophysiology that warrants detailed investigation.…”

Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease

“…It has been demonstrated that Se levels in the CSF of PD patients were significantly higher than those in controls [ 97 , 98 ]. In experimental studies, Se treatment exhibits neuroprotective effects in parkinsonian models [ 99 , 100 , 101 ]. Ellwanger et al reported that Se administration reduced DNA damage and bradykinesia in parkinsonian rats injected with paraquat, which is a pesticide associated with increased risk for developing PD [ 99 ].…”

“…Ellwanger et al reported that Se administration reduced DNA damage and bradykinesia in parkinsonian rats injected with paraquat, which is a pesticide associated with increased risk for developing PD [ 99 ]. Sun et al demonstrated that administration of sodium selenite increased GPx activity and provided neuroprotective effects in 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-injected parkinsonian mice [ 100 ]. It is still unknown whether MTs can function in the maintenance of Se; however, it is reported that sodium selenite induces MTs in mice.…”

Physiological Benefits of Novel Selenium Delivery via Nanoparticles

“…Therefore, on this basis selenomethionine is commonly used in feed for intensive poultry practices [ 6 , 41 ]. However, the inorganic forms are readily absorbed and in general the available evidence indicates inorganic Se displays enhanced protective effects against certain pathologies, including Parkinson’s disease [ 42 , 43 ]. Thus, sodium selenite has also ameliorated intestinal inflammation and histological damage in colitis mouse models via downregulation of proinflammatory cytokines and certain T-cell populations, with a concomitant upregulation of anti-inflammatory cytokines [ 44 ].…”