Selenomethionine promoted hippocampal neurogenesis via the PI3K-Akt-GSK3β-Wnt pathway in a mouse model of Alzheimer's disease

Zheng, Rui; Zhang, Zhonghao; Chen, Chen; Chen, Yao; Jia, Shi-Zheng; Liu, Qiong; Ni, Jiazuan; Song, Guo-Li

doi:10.1016/j.bbrc.2017.01.069

Cited by 62 publications

(35 citation statements)

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“…A deleterious effect of Se(VI) on the central nervous system (CNS), and more generally inorganic Se, is biologically plausible, since these Se compounds have been long known to be very toxic [ 24 , 55 ]. Such an effect would contrast with suggestions of potential beneficial effects of Se and selenoproteins in AD progression from laboratory studies [ 56 – 58 ], although this hypothesis was recently contradicted by results from the PREADVISE study (Prevention of Alzheimer’s Disease by Vitamin E and Selenium Trial) [ 32 ]. In that trial, 7540 asymptomatic older adults in North America were randomized to either placebo or 200 μg/day Se as l -selenomethionine or both l -selenomethionine and vitamin E for an average of 5.4 years, but there was no effect of any Se supplementation on dementia or AD incidence during the active supplementation period, or within a subset of the study cohort up to 6 additional years [ 32 ].…”

Section: Discussionmentioning

confidence: 93%

A selenium species in cerebrospinal fluid predicts conversion to Alzheimer’s dementia in persons with mild cognitive impairment

et al. 2017

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BackgroundLittle is known about factors influencing progression from mild cognitive impairment to Alzheimer’s dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form.MethodsWe determined concentrations of selenium species in cerebrospinal fluid sampled at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin. We then investigated the relation of these concentrations to subsequent conversion from mild cognitive impairment to Alzheimer’s dementia.ResultsTwenty-one out of the 56 subjects developed Alzheimer’s dementia during a median follow-up of 42 months; four subjects developed frontotemporal dementia and two patients Lewy body dementia. In a Cox proportional hazards model adjusting for age, sex, duration of sample storage, and education, an inorganic selenium form, selenate, showed a strong association with Alzheimer’s dementia risk, with an adjusted hazard ratio of 3.1 (95% confidence interval 1.0–9.5) in subjects having a cerebrospinal fluid content above the median level, compared with those with lower concentration. The hazard ratio of Alzheimer’s dementia showed little departure from unity for all other inorganic and organic selenium species. These associations were similar in analyses that measured exposure on a continuous scale, and also after excluding individuals who converted to Alzheimer’s dementia at the beginning of the follow-up.ConclusionsThese results indicate that higher amounts of a potentially toxic inorganic selenium form in cerebrospinal fluid may predict conversion from mild cognitive impairment to Alzheimer’s dementia.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-017-0323-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 93%

A selenium species in cerebrospinal fluid predicts conversion to Alzheimer’s dementia in persons with mild cognitive impairment

et al. 2017

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“…Se treatment increases the use of direct spatial strategies (e.g., direct swimming, focal search…) resulting likely in memory improvement in 3xTg-AD mice. Indeed, sodium selenate and selenomethionine increase spatial learning in the water maze in young AD transgenic mice 20 , 22 , 41 , and a multi-nutrient diet containing Se alleviates cognitive deficits in APP/PS1 mice by increasing the use of navigation search strategies 39 . This effect was mediated by reduction of Aβ and amyloid plaques in young APP/PS1 mice, while it was independent of brain amyloid pathology in old mice 39 , 42 .…”

Section: Discussionmentioning

confidence: 99%

Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice

Jeugd

Parra-Damas

Baeta-Corral

et al. 2018

Sci Rep

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Accumulation of amyloid-β plaques and tau contribute to the pathogenesis of Alzheimer’s disease (AD), but it is unclear whether targeting tau pathology by antioxidants independently of amyloid-β causes beneficial effects on memory and neuropsychiatric symptoms. Selenium, an essential antioxidant element reduced in the aging brain, prevents development of neuropathology in AD transgenic mice at early disease stages. The therapeutic potential of selenium for ameliorating or reversing neuropsychiatric and cognitive behavioral symptoms at late AD stages is largely unknown. Here, we evaluated the effects of chronic dietary sodium selenate supplementation for 4 months in female 3xTg-AD mice at 12–14 months of age. Chronic sodium selenate treatment efficiently reversed hippocampal-dependent learning and memory impairments, and behavior- and neuropsychiatric-like symptoms in old female 3xTg-AD mice. Selenium significantly decreased the number of aggregated tau-positive neurons and astrogliosis, without globally affecting amyloid plaques, in the hippocampus of 3xTg-AD mice. These results indicate that selenium treatment reverses AD-like memory and neuropsychiatric symptoms by a mechanism involving reduction of aggregated tau and/or reactive astrocytes but not amyloid pathology. These results suggest that sodium selenate could be part of a combined therapeutic approach for the treatment of memory and neuropsychiatric symptoms in advanced AD stages.

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Section: Wnt Signaling In the Impairment Of Neurogenesis In Alzheimermentioning

confidence: 99%

“…In addition, the biological trace element Selenomethionine (Se-Met) and Ethosuximide (ETH), which inactivate GSK-3β through the PI3K/Akt pathway, also promoted neurogenesis in AD models (Tiwari et al, 2015;Zheng et al, 2017). Together with the inactivation of GSK-3β, Se-Met increased β-catenin levels, induced the expression of Cyclin D1, and increased cell proliferation and neurogenesis in the hippocampus of a 3xTg AD mice (Zheng et al, 2017). On the other hand, treatment with the antiepileptic drug ETH, reversed cognitive dysfunction, and increased proliferation and neuronal differentiation in the dentate gyrus of a rat model of AD induced by the injection of Aβ (1-42) into the hippocampus (Tiwari et al, 2015).…”

Section: Wnt Signaling In the Impairment Of Neurogenesis In Alzheimermentioning

confidence: 99%

Role of Wnt Signaling in Adult Hippocampal Neurogenesis in Health and Disease

Arredondo

Valenzuela-Bezanilla

Mardones

et al. 2020

Front. Cell Dev. Biol.

102

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Neurogenesis persists during adulthood in the dentate gyrus of the hippocampus. Signals provided by the local hippocampal microenvironment support neural stem cell proliferation, differentiation, and maturation of newborn neurons into functional dentate granule cells, that integrate into the neural circuit and contribute to hippocampal function. Increasing evidence indicates that Wnt signaling regulates multiple aspects of adult hippocampal neurogenesis. Wnt ligands bind to Frizzled receptors and co-receptors to activate the canonical Wnt/β-catenin signaling pathway, or the noncanonical β-catenin-independent signaling cascades Wnt/Ca 2+ and Wnt/planar cell polarity. Here, we summarize current knowledge on the roles of Wnt signaling components including ligands, receptors/co-receptors and soluble modulators in adult hippocampal neurogenesis. Also, we review the data suggesting distinctive roles for canonical and non-canonical Wnt signaling cascades in regulating different stages of neurogenesis. Finally, we discuss the evidence linking the dysfunction of Wnt signaling to the decline of neurogenesis observed in aging and Alzheimer's disease.

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Selenomethionine promoted hippocampal neurogenesis via the PI3K-Akt-GSK3β-Wnt pathway in a mouse model of Alzheimer's disease

Cited by 62 publications

References 50 publications

A selenium species in cerebrospinal fluid predicts conversion to Alzheimer’s dementia in persons with mild cognitive impairment

A selenium species in cerebrospinal fluid predicts conversion to Alzheimer’s dementia in persons with mild cognitive impairment

Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice

Role of Wnt Signaling in Adult Hippocampal Neurogenesis in Health and Disease

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