Long-Term Dietary Supplementation with Selenium-Enriched Yeast Improves Cognitive Impairment, Reverses Synaptic Deficits, and Mitigates Tau Pathology in a Triple Transgenic Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by multiple histopathological changes in the brain and by impairments in memory and cognitive function. Currently, there is no effective treatment that can halt or reverse the progression of this disease. Here, we explored the effects of 3 months of treatment with selenium-enriched yeast (Se-yeast), which is commonly used as a source of organic selenium (Se) for nutrition, on cognitive dysfunction and neuropathology in the triple transgenic mouse model of AD (3×Tg-AD mice). As the results revealed that Se-yeast significantly improved the spatial learning and memory retention of 3×Tg-AD mice, promoted neuronal activity, attenuated the activation of astrocytes and microglia, mitigated synaptic deficits, and reduced the levels of total tau and phosphorylated tau though inhibiting the activity of GSK-3β, dietary supplementation with Se-yeast exerted multiple beneficial effects on the prevention or treatment of AD. These findings provide evidence of a potentially viable compound for AD treatment.

Selenium in Human Health and Gut Microflora: Bioavailability of Selenocompounds and Relationship With Diseases

“…Tau is the main protein associated with the stability of neuronal microtubules along with the MAPs (MAP1 and MAP2) (166). Long-term dietary supplementation (3 months) with Seenriched yeast (Se-yeast) in triple transgenic mouse model of Alzheimer disease (AD), significantly improved spatial learning, retention of neuronal memory and activity (167).…”

Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer’s Disease

“…Consistently with this data, there is also experimental evidence of positive outcomes in 3x-Tg mice that were given selenium-enriched yeast for 3 months. Interestingly, spatial memory was improved concomitantly with reduced neuroinflammation, GSK3β-dependent Tau phosphorylation and increased expression of synaptic proteins in the cortex and hippocampus (Zhang et al, 2017). In the same line, in a pilot study and a larger RCT (Kobayashi et al, 2019a,b), analyzed the impact of a 6-or 3-month probiotic supplementation with Bifidobacterium breve A1 in aged patients with MCI, respectively.…”

Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

“…Organic Se has attracted attention due to its advantages, including its enhanced biological activity, decreased toxicity, and diminished environmental pollution concern compared to inorganic Se. Many organic Se compounds have been shown to have therapeutic effects in AD mice models (Xie et al, 2017(Xie et al, , 2018Zhang et al, 2017aZhang et al, , 2018. Through a series of studies, Zhang et al showed that selenomethionine enhanced the antioxidant capacity, mitigated Aβ and tau pathology, reversed synaptic deficits, and ameliorated cognitive decline in AD mice (Song et al, 2014;Zhang et al, 2016Zhang et al, , 2017aZhang et al, , 2018, demonstrating the multitarget effect of Se in AD treatment.…”

“…Many organic Se compounds have been shown to have therapeutic effects in AD mice models (Xie et al, 2017(Xie et al, , 2018Zhang et al, 2017aZhang et al, , 2018. Through a series of studies, Zhang et al showed that selenomethionine enhanced the antioxidant capacity, mitigated Aβ and tau pathology, reversed synaptic deficits, and ameliorated cognitive decline in AD mice (Song et al, 2014;Zhang et al, 2016Zhang et al, , 2017aZhang et al, , 2018, demonstrating the multitarget effect of Se in AD treatment. Furthermore, impaired autophagy (Zhang et al, 2017b,c;Song et al, 2018) and mitochondrial dysfunction (Balaban et al, 2017) have been shown to be the targets of Se compounds in AD.…”