Loss of MsrB1 perturbs spatial learning and long-term potentiation/long-term depression in mice

Shi, Tengrui; Yang, Yujie; Zhang, Zhonghao; Zhang, Lei; Song, Jianxi; Ping, Yongjing; Du, Xiubo; Song, Guo-Li; Liu, Qiong; Li, Nan

doi:10.1016/j.nlm.2019.107104

Cited by 15 publications

(8 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, neuron-specific GPX4-knockout mice and Selenop −/− mice have spontaneous seizures since the corresponding regions (the cortical region in GPX4-knockout mice and the inferior colliculus in Selenop −/− mice) in the brain lack PV-expressing GABAergic interneurons (Wirth et al, 2010;Pitts et al, 2012Pitts et al, , 2015, suggesting that GPX4 and SELENOP participate in the process of GABAergic neuron transduction. Although SELENOR deficiency does not interfere with CNS development, the significantly downregulated expression levels of synaptic proteins and the synaptic receptor NMDAR can substantially affect the persistence of long-term potentiation and long-term depression (LTP/LTD) in the hippocampal CA1 region of the mouse brain (Shi et al, 2019). A study by Boukhzar et al (2016) confirmed that SELENOT was necessary for dopamine production by dopaminergic neurons in PD model mice.…”

Section: Synaptic Function and Neurotransmissionmentioning

confidence: 98%

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

Zhang

Song

2021

Front. Neurosci.

View full text Add to dashboard Cite

Selenium (Se) and its compounds have been reported to have great potential in the prevention and treatment of Alzheimer’s disease (AD). However, little is known about the functional mechanism of Se in these processes, limiting its further clinical application. Se exerts its biological functions mainly through selenoproteins, which play vital roles in maintaining optimal brain function. Therefore, selenoproteins, especially brain function-associated selenoproteins, may be involved in the pathogenesis of AD. Here, we analyze the expression and distribution of 25 selenoproteins in the brain and summarize the relationships between selenoproteins and brain function by reviewing recent literature and information contained in relevant databases to identify selenoproteins (GPX4, SELENOP, SELENOK, SELENOT, GPX1, SELENOM, SELENOS, and SELENOW) that are highly expressed specifically in AD-related brain regions and closely associated with brain function. Finally, the potential functions of these selenoproteins in AD are discussed, for example, the function of GPX4 in ferroptosis and the effects of the endoplasmic reticulum (ER)-resident protein SELENOK on Ca2+ homeostasis and receptor-mediated synaptic functions. This review discusses selenoproteins that are closely associated with brain function and the relevant pathways of their involvement in AD pathology to provide new directions for research on the mechanism of Se in AD.

show abstract

Section: Synaptic Function and Neurotransmissionmentioning

confidence: 98%

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

Zhang

Song

2021

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…As for another selenoenzyme, MsrB1 (previously called SELENOR), its level was significantly increased in the SeNa-treated group. Interestingly, numerous studies have indicated an association between GPx1 and Aβ pathology [ 43 , 44 ], modulation of phosphorylated GSK-3β by TrxR activity [ 45 , 46 ], and the effects of SELENOR on synaptic function [ 47 ]. Therefore, our results indicate that different Se compounds induce the activity and expression of different selenoenzymes in the brains of AD mice, which may be the fundamental reason for their different effects on AD pathology.…”

Section: Discussionmentioning

confidence: 99%

Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease

et al. 2023

View full text Add to dashboard Cite

Owing to the strong antioxidant capacity of selenium (Se) in vivo, a variety of Se compounds have been shown to have great potential for improving the main pathologies and cognitive impairment in Alzheimer’s disease (AD) models. However, the differences in the anti-AD effects and mechanisms of different Se compounds are still unclear. Theoretically, the absorption and metabolism of different forms of Se in the body vary, which directly determines the diversification of downstream regulatory pathways. In this study, low doses of Se-methylselenocysteine (SMC), selenomethionine (SeM), or sodium selenate (SeNa) were administered to triple transgenic AD (3× Tg-AD) mice for short time periods. AD pathology, activities of selenoenzymes, and metabolic profiles in the brain were studied to explore the similarities and differences in the anti-AD effects and mechanisms of the three Se compounds. We found that all of these Se compounds significantly increased Se levels and antioxidant capacity, regulated amino acid metabolism, and ameliorated synaptic deficits, thus improving the cognitive capacity of AD mice. Importantly, SMC preferentially increased the expression and activity of thioredoxin reductase and reduced tau phosphorylation by inhibiting glycogen synthase kinase-3 beta (GSK-3β) activity. Glutathione peroxidase 1 (GPx1), the selenoenzyme most affected by SeM, decreased amyloid beta production and improved mitochondrial function. SeNa improved methionine sulfoxide reductase B1 (MsrB1) expression, reflected in AD pathology as promoting the expression of synaptic proteins and restoring synaptic deficits. Herein, we reveal the differences and mechanisms by which different Se compounds improve multiple pathologies of AD and provide novel insights into the targeted administration of Se-containing drugs in the treatment of AD.

show abstract

“…Since we found that CREB phosphorylation is increased in AD model mice and in hippocampal neurons challenged with oAβ 1–42 , we hypothesise that CaMKIIα oxidation would be a protective mechanism triggered by neurons after being challenged by oAβ 1–42 . This mechanism is a steady low active state, while phosphorylation is able to transduce potent calcium signalling [ 9 , 10 , 28 , 29 ]. This potent calcium signalling leads to an exponential threshold signalling necessary for the induction of LTP through phosphorylation of CREB at S133, S142 and S143 [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Amyloid β-Peptide Causes the Permanent Activation of CaMKIIα through Its Oxidation

Picón-Pagès

Fanlo-Ucar

Herrera-Fernández

et al. 2022

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is characterised by the presence of extracellular amyloid plaques in the brain. They are composed of aggregated amyloid beta-peptide (Aβ) misfolded into beta-sheets which are the cause of the AD memory impairment and dementia. Memory depends on the hippocampal formation and maintenance of synapses by long-term potentiation (LTP), whose main steps are the activation of NMDA receptors, the phosphorylation of CaMKIIα and the nuclear translocation of the transcription factor CREB. It is known that Aβ oligomers (oAβ) induce synaptic loss and impair the formation of new synapses. Here, we have studied the effects of oAβ on CaMKIIα. We found that oAβ produce reactive oxygen species (ROS), that induce CaMKIIα oxidation in human neuroblastoma cells as we assayed by western blot and immunofluorescence. Moreover, this oxidized isoform is significantly present in brain samples from AD patients. We found that the oxidized CaMKIIα is active independently of the binding to calcium/calmodulin, and that CaMKIIα phosphorylation is mutually exclusive with CaMKIIα oxidation as revealed by immunoprecipitation and western blot. An in silico modelling of the enzyme was also performed to demonstrate that oxidation induces an activated state of CaMKIIα. In brains from AD transgenic models of mice and in primary cultures of murine hippocampal neurons, we demonstrated that the oxidation of CaMKIIα induces the phosphorylation of CREB and its translocation to the nucleus to promote the transcription of ARC and BDNF. Our data suggests that CaMKIIα oxidation would be a pro-survival mechanism that is triggered when a noxious stimulus challenges neurons as do oAβ.

show abstract

Loss of MsrB1 perturbs spatial learning and long-term potentiation/long-term depression in mice

Cited by 15 publications

References 47 publications

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

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

Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease

Amyloid β-Peptide Causes the Permanent Activation of CaMKIIα through Its Oxidation

Contact Info

Product

Resources

About