Essential Trace Element Selenium Research Articles

Combined copper and zinc deficiency is associated with reduced SARS-CoV-2 immunization response to BNT162b2 vaccination

The essential trace elements copper, selenium and zinc are of relevance for immunity and immune response to vaccination. In this longitudinal study, adult healthcare workers (n = 126) received two doses of an mRNA vaccine (BNT162b2), and longitudinal serum samples were prepared. Vaccine-induced antibodies and their neutralizing activity were analyzed, and the trace elements copper, zinc, and selenium along with the copper transporter ceruloplasmin were measured. Subjects with combined deficiency of copper and zinc, i.e. both in the lowest tertiles at baseline, displayed particularly low antibody titers at three (Double Q1: 13 AU/mL vs. not double Q1: 29 AU/mL) and six (Double Q1: 200 AU/mL vs. not double Q1: 425 AU/mL) weeks after vaccination (p < 0.05). The results indicate the potential importance of an adequate trace element status of copper and zinc for raising a strong vaccine-induced SARS-CoV-2 antibody response, and highlights the importance of considering combined micronutrient insufficiencies, as single deficiencies may synergize.

The ionome and proteome landscape of aging in laying hens and relation to egg white quality.

The ionome is essential for maintaining body function and health status by participating in diverse key biological processes. Nevertheless, the distribution and utilization of ionome among different organs and how aging impacts the ionome leading to a decline in egg white quality remain unknown. Thus, we used inductively coupled plasma mass spectrometry (ICP-MS) to analyze 35 elements and their isotopic contents in eight organs of laying hens at 35, 72, and 100 weeks. Moreover, the magnum proteome, amino acids in egg white, and egg white quality were analyzed in laying hens at three different ages using 4D proteomics techniques, an amino acid analyzer, and an egg quality analyzer. Across the organs, we identified varying distribution patterns among macroelements (Mg24, Ca43/44, K39, and P31), transition metals (Zn64/66, Cu63/65, Fe56/57, and Mn55), and toxic elements (Pb208, Ba137, and Sr86). We observed an organ-specific aging pattern characterized by the accumulation of toxic elements (Pb208, Ba137, and Sr86) and calcification in the small intestine. Additionally, a decrease in the utilization of essential trace elements selenium (Se78/82) and manganese (Mn55) was noted in the oviduct. By analyzing ionome in tandem with egg quality, egg white amino acids, and proteome, we unveiled that the reduction of selenium and manganese concentrations in the magnum during the aging process affected amino acid metabolism, particularly tryptophan metabolism, thereby inhibiting the amino acid synthesis in the magnum. Furthermore, it accelerated the senescence of magnum cells through necroptosis activation, leading to a decline in the albumen secretion function of the magnum and subsequently reducing egg white quality. Overall, this study provides insights into the evolution of 35 elements and their isotopes across 8 organs of laying hens with age. It also reveals the elemental composition, interactions, and utilization patterns of these organs, as well as their correlation with egg white quality. The present study highlights the significance of ionome and offers a comprehensive perspective on the selection of ionome for regulating the aging of laying hens.

The Impact of Essential Trace Elements on Ovarian Response and Reproductive Outcomes following Single Euploid Embryo Transfer.

Essential trace elements are required in extremely small amounts and obtained through diet. This research focuses on detecting major trace elements in different biofluids of sixty women undergoing ICSI with PGT-A and SET/FET at IVI-RMA, New Jersey, and assessing their impact on their IVF outcomes. Urine, plasma, and follicular fluid samples were collected on the vaginal oocyte retrieval day to measure the concentrations of eight essential trace elements (copper, zinc, molybdenum, lithium, selenium, manganese, chromium, and iron) using ICP-MS. After analysis, ovarian response and preimplantation outcomes had significant positive associations with both copper alone and the copper/zinc ratio in the follicular fluid and plasma, in addition to plasma manganese. Alternatively, elevated follicular fluid lithium concentrations were significantly associated with poor preimplantation outcomes while the urinary molybdenum concentration was significantly associated with a lower probability of implantation, clinical pregnancy, and live birth. Urinary lithium and chromium concentrations were significantly associated with a lower probability of achieving a live birth. Our results suggest that the essential trace elements present in follicular fluid, plasma, and urine of women are directly associated with their reproductive outcomes, with copper and manganese exerting positive effects and lithium and molybdenum exerting negative effects.

Selenium suppressed the LPS-induced inflammation of bovine endometrial epithelial cells through NF-κB and MAPK pathways under high cortisol background.

The bovine uterus is susceptible to infection, and the elevated cortisol level due to stress are common in cows after delivery. The essential trace element selenium plays a pivotal role in the antioxidant and anti-inflammatory defence system of body. This study investigated whether selenium supplementation protected endometrial cells from inflammation in the presence of high-level cortisol. The primary bovine endometrial epithelial cells were subjected to Escherichia coli lipopolysaccharide to establish cellular inflammation model. The gene expression of inflammatory mediators and proinflammatory cytokines was measured by quantitative PCR. The key proteins of NF-κB and MAPK signalling pathways were detected by Western blot and immunofluorescence. The result showed that pre-treatment of Na2 SeO3 (1, 2 and 4 μΜ) decreased the mRNA expression of proinflammatory genes, inhibited the activation of NF-κB and suppressed the phosphorylation of extracellular signal-regulated kinase, P38MAPK and c-Jun N-terminal kinase. This inhibition of inflammation was more apparent in the presence of high-level cortisol (30 ng/mL). These results indicated that selenium has an anti-inflammatory effect, which is mediated via NF-κB and MAPK signalling pathways and is augmented by cortisol in bovine endometrial epithelial cells.

Prolonged maternal exposure to glucocorticoids alters selenoprotein expression in the developing brain.

Aberrant activation of the stress-response system in early life can alter neurodevelopment and cause long-term neurological changes. Activation of the hypothalamic-pituitary-adrenal axis releases glucocorticoids into the bloodstream, to help the organism adapt to the stressful stimulus. Elevated glucocorticoid levels can promote the accumulation of reactive oxygen species, and the brain is highly susceptible to oxidative stress. The essential trace element selenium is obtained through diet, is used to synthesize antioxidant selenoproteins, and can mitigate glucocorticoid-mediated oxidative damage. Glucocorticoids can impair antioxidant enzymes in the brain, and could potentially influence selenoprotein expression. We hypothesized that exposure to high levels of glucocorticoids would disrupt selenoprotein expression in the developing brain. C57 wild-type dams of recently birthed litters were fed either a moderate (0.25 ppm) or high (1 ppm) selenium diet and administered corticosterone (75 μg/ml) via drinking water during postnatal days 1 to 15, after which the brains of the offspring were collected for western blot analysis. Glutathione peroxidase 1 and 4 levels were increased by maternal corticosterone exposure within the prefrontal cortex, hippocampus, and hypothalamus of offspring. Additionally, levels of the glucocorticoid receptor were decreased in the hippocampus and selenoprotein W was elevated in the hypothalamus by corticosterone. Maternal consumption of a high selenium diet independently decreased glucocorticoid receptor levels in the hippocampus of offspring of both sexes, as well as in the prefrontal cortex of female offspring. This study demonstrates that early life exposure to excess glucocorticoid levels can alter selenoprotein levels in the developing brain.

Selenium homeostasis in human brain cells: Effects of copper (II) and Se species

BackgroundBoth essential trace elements selenium (Se) and copper (Cu) play an important role in maintaining brain function. Homeostasis of Cu, which is tightly regulated under physiological conditions, seems to be disturbed in Alzheimer´s (AD) and Parkinson´s disease (PD) patients. Excess Cu promotes the formation of oxidative stress, which is thought to be a major cause for development and progression of neurological diseases (NDs). Most selenoproteins exhibit antioxidative properties and may counteract oxidative stress. However, expression of selenoproteins is altered under conditions of Se deficiency. Serum Se levels are decreased in AD and PD patients suggesting Se as an important factor in the development and progression of NDs. The aim of this study was to elucidate the interactions between Cu and Se in human brain cells particularly with respect to Se homeostasis. MethodsFirstly, modulation of Se status by selenite or SeMet were assessed in human astrocytes and human differentiated neurons. Therefore, cellular total Se content, intra- and extracellular selenoprotein P (SELENOP) content, and glutathione peroxidase (GPX) activity were quantified. Secondly, to investigate the impact of Cu on these markers, cells were exposed to copper(II)sulphate (CuSO4) for 48 h. In addition, putative protective effects of Se on Cu-induced toxicity, as measured by cell viability, DNA damage, and neurodegeneration were investigated. ResultsModulation of cellular Se status was strongly dependent on Se species. In detail, SeMet increased total cellular Se and SELENOP content, whereas selenite led to increased GPX activity and SELENOP excretion. Cu treatment resulted in 133-fold higher cellular Cu concentration with a concomitant decrease in Se content. Additionally, SELENOP excretion was suppressed in both cell lines, while GPX activity was diminished only in astrocytes. These effects of Cu could be partially prevented by the addition of Se depending on the cell line and Se species used. While Cu-induced oxidative DNA damage could not be prevented by addition of Se regardless of chemical species, SeMet protected against neurite network degeneration triggered by Cu. ConclusionCu appears to negatively affect Se status in astrocytes and neurons. Especially with regard to an altered homeostasis of those trace elements during aging, this interaction is of high physiological relevance. Increasing Cu concentrations associated with decreased selenoprotein expression or functionality might be a promoting factor for the development of NDs.

Trace Minerals and Anxiety: A Review of Zinc, Copper, Iron, and Selenium

Anxiety disorder is characterized by excessive fear or avoidance of perceived threats that can be persistent and debilitating. Diet is a modifiable risk factor that may contribute to the pathogenesis or treatment of anxiety, depending on diet quality. Although the biological mechanisms by which food, specific nutrients, and nutraceuticals impact mental health are not completely understood, implicated pathways include inflammation, oxidative stress, brain plasticity effects, mitochondrial dysfunction, and neurotransmitter metabolism. Essential dietary trace minerals such as zinc, copper, iron, and selenium are critical components for numerous biological proteins and may have a role in these proposed mechanisms related to brain health and anxiety. This narrative review examines the influence of essential trace elements zinc, copper, iron, and selenium on anxiety symptoms based on the latest peer-reviewed scientific evidence. Current research indicates that deficiencies in zinc, iron, and selenium are associated with anxiety, while copper overload may impact anxiety to a greater degree than copper deficiency. Further investigation is needed to understand the specific neurobiological mechanisms involved. Overall, the collective findings demonstrate the importance of optimizing trace mineral homeostasis for the mitigation of anxiety disorders and preservation of mental health.

Low selenium intake is associated with risk of all-cause mortality in kidney transplant recipients.

Deficiency of the essential trace element selenium is common in kidney transplant recipients (KTR), potentially hampering antioxidant and anti-inflammatory defence. Whether this impacts the long-term outcomes of KTR remains unknown. We investigated the association of urinary selenium excretion, a biomarker of selenium intake, with all-cause mortality; and its dietary determinants. In this cohort study, outpatient KTR with a functioning graft for longer than 1 year were recruited (2008-11). Baseline 24-h urinary selenium excretion was measured by mass spectrometry. Diet was assessed by a 177-item food frequency questionnaire, and protein intake was calculated by the Maroni equation. Multivariable linear and Cox regression analyses were performed. In 693 KTR (43% men, 52±12 years), baseline urinary selenium excretion was 18.8 (interquartile range 15.1-23.4) μg/24-h. During a median follow-up of 8 years, 229 (33%) KTR died. KTR in the first tertile of urinary selenium excretion, compared with those in the third, had over a 2-fold risk of all-cause mortality [hazard ratio 2.36 (95% confidence interval 1.70-3.28); P<.001], independent of multiple potential confounders including time since transplantation and plasma albumin concentration. The most important dietary determinant of urinary selenium excretion was protein intake (Standardized β 0.49, P<.001). Relatively low selenium intake is associated with a higher risk of all-cause mortality in KTR. Dietary protein intake is its most important determinant. Further research is required to evaluate the potential benefit of accounting for selenium intake in the care of KTR, particularly among those with low protein intake.

Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice

Despite progress in reperfusion therapy, functional recovery remains suboptimal in many stroke patients, with oxidative stress, inflammation, dysbiosis, and secondary neurodegeneration constituting the major hurdles to recovery. The essential trace element selenium is emerging as a promising therapeutic agent for stroke. However, although several rodent studies have shown that selenium can protect against cell loss following cerebral ischemia, no study has yet examined whether selenium can enhance long-term functional recovery. Moreover, published studies have typically reported a single mechanism of action underlying selenium-mediated stroke recovery. However, we propose that selenium is more likely to have multifaceted actions. Here, we show that selenomethionine confers a potent neuroprotective effect in a canonical filament-induced transient middle cerebral artery occlusion (tMCAO) mouse model. Post-tMCAO selenium treatment significantly reduces the cerebral infarct volume, oxidative stress, and ferroptosis and enhances post-tMCAO motor performance in the acute phase after stroke. Moreover, analysis of the gut microbiota reveals that acute selenium treatment reverses stroke-induced gut dysbiosis. Longer-term selenium supplementation activates intrinsic neuroprotective mechanisms, prevents secondary neurodegeneration, alleviates systemic inflammation, and diminishes gut microbe-derived circulating trimethylamine N-oxide. These findings demonstrate that selenium treatment even after cerebral ischemia has long-term and multifaceted neuroprotective effects, highlighting its clinical potential.

Clinical and inflammatory biomarkers of inflammatory bowel diseases are linked to plasma trace elements and toxic metals; new insights into an old concept.

Inflammatory bowel diseases (IBD) are chronic immune-mediated diseases, mainly represented by Crohn's disease (CD) and ulcerative colitis (UC). Several environmental factors have been proposed to contribute to disease pathogenesis, amongst which are metals. These can affect the immune system and may be associated with IBD. The aim of the present cross-sectional study was to investigate blood levels of metals in IBD patients and to examine possible associations with clinical and inflammatory disease markers. In total, 76 CD patients, 39 UC patients and 38 healthy controls were included. Blood and stool samples were collected. Metals were quantified in plasma samples using inductively coupled plasma mass spectrometry. There were more abnormalities of circulating metals in CD than in UC when compared to healthy controls. CD: Concentrations of the essential trace elements zinc and selenium were lower in CD patients than the controls. Chromium was negatively associated with serum IL-6 (Beta: -3.558, p = 0.011), and caesium with fecal calprotectin (Beta: -0.481, p = 0.038) and serum IL-10 (Beta: -1.912, p = 0.050). In contrast, copper was positively associated with C-reactive protein (Beta: 2.548 × 102, p = 0.033). UC: In UC, a negative association of iron with serum myeloperoxidase levels (Beta: -1.270 × 103, p = 0.044) was detected. Thallium, a hazardous metal, however, was positively associated with disease activity (Beta: 3.899, p = < 0.01). In conclusion, our study offers new insights into the relations of metals with IBD. Further research should focus on the evaluation of the above associations and potential underlying mechanisms.

Selenium in Bodily Homeostasis: Hypothalamus, Hormones, and Highways of Communication

The ability of the body to maintain homeostasis requires constant communication between the brain and peripheral tissues. Different organs produce signals, often in the form of hormones, which are detected by the hypothalamus. In response, the hypothalamus alters its regulation of bodily processes, which is achieved through its own pathways of hormonal communication. The generation and transmission of the molecules involved in these bi-directional axes can be affected by redox balance. The essential trace element selenium is known to influence numerous physiological processes, including energy homeostasis, through its various redox functions. Selenium must be obtained through the diet and is used to synthesize selenoproteins, a family of proteins with mainly antioxidant functions. Alterations in selenium status have been correlated with homeostatic disturbances in humans and studies with animal models of selenoprotein dysfunction indicate a strong influence on energy balance. The relationship between selenium and energy metabolism is complicated, however, as selenium has been shown to participate in multiple levels of homeostatic communication. This review discusses the role of selenium in the various pathways of communication between the body and the brain that are essential for maintaining homeostasis.

Benefits and risks of essential trace elements in chronic kidney disease: a narrative review.

Chronic kidney disease (CKD) is an important public health concern. With the decline of renal function, CKD patients gradually progress to end-stage kidney disease and need to undergo dialysis or kidney transplantation to maintain life, bringing a heavy economic burden to the family and society. Therefore, it is necessary to effectively prevent and delay the progression of CKD. Essential trace elements play an indispensable role in CKD, and the objective of this study is to systematically review their benefits in the disease and summarize the risks of their excess. The keywords "trace elements", "chronic kidney disease", "dialysis", "inflammation", and "fibrosis" and their combinations were used to search for relevant literature published in the PubMed database and Web of Science. We then summarized the role of trace element abnormalities in CKD patients in anemia, oxidative stress, inflammation, and chronic fibrosis, and the risk of their excess. Imbalance of essential trace elements is a common complication of CKD and a risk factor for CKD progression, cardiovascular events, and death. This article reviews the effects of essential trace elements (iron, zinc, selenium, copper, iodine, and manganese) on CKD. We analyze literature and discuss the advantages and disadvantages of various essential trace elements. Research shows CKD patients have an imbalance of essential trace elements, and treatment based on these is an important direction for future exploration. A knowledge of the homeostasis of trace elements is important to improving the prognosis of CKD patients and delaying the progression of the disease.

The association between essential trace element (copper, zinc, selenium, and cobalt) status and the risk of early embryonic arrest among women undergoing assisted reproductive techniques.

Early embryonic arrest (EEA) leads to repeated cessation of fresh cycles among infertile women undergoing in vitro fertilization (IVF). Whether the levels of some essential trace elements [copper (Cu), zinc (Zn), selenium (Se) and cobalt (Co)] in the bodies of women are related to the risk of EEA warrants study. Our study aimed to investigate the associations of peripheral blood levels of Cu, Zn, Se, and Co and their mixtures with the risk of EEA. A total of 74 EEA cases (123 IVF cycles) and 157 controls (180 IVF cycles) from the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between June 2017 and March 2020 were included in our study. Demographic and clinical data were collected from electronic medical records. Cu, Zn, Se, and Co levels were measured in blood samples collected on the day of oocyte retrieval when infertile women entered clinical treatment for the first time using an inductively coupled plasma mass spectrometer (ICP-MS). Generalized estimating equation (GEE) models were used to evaluate the associations of four essential trace element concentrations individually with the risk of EEA, and Bayesian kernel machine regression (BKMR) was used to explore the associations between four essential trace element mixtures and the risk of EEA. Se concentrations of infertile women were significantly lower in the case group compared with the control group. Co levels were significantly higher in the case group compared with the control group. The differences in Cu and Zn concentrations between the two groups were not significant. Based on single-metal models, Co was positively associated with the risk of EEA before and after adjustment for all confounders (odd ratio (OR) = 1.72, 95% confidence interval (CI): 1.18-2.52; OR = 2.27, 95% CI: 1.37-3.77, respectively), and Se was negatively associated with the risk of EEA before adjustment for all confounders (OR = 0.18, 95% CI: 0.07-0.51). BKMR analyses showed that Se was significantly and negatively associated with the risk of EEA when all the other three metals (Cu, Zn, and Co) were fixed at the 25th, 50th, or 75th percentiles, whereas Zn displayed a significant and positive association with the risk of EEA when all the other three metals (Cu, Se and Co) were fixed at the 25th, 50th, or 75th percentiles. Co did not show any effect on the risk of EEA when all the other metals (Cu, Zn, and Se) were fixed at the 25th, 50th, or 75th percentiles. In addition, an increasing trend of the joint effect of four essential trace elements on the risk of EEA was found, although it was not statistically significant. The levels of essential trace elements (Cu, Zn, Se, and Co) might correlate with the risk of EEA to some extent. The present study might provide a real-world perspective on the relationship between essential trace elements and the risk of EEA when considering them as a single element or as mixtures.

Exopolymer-Functionalized Nanoselenium from Bacillus subtilis SR41: Characterization, Monosaccharide Analysis and Free Radical Scavenging Ability.

To provide a safe and effective supplement of the essential trace element selenium, we focused on the biosynthesis of nanoselenium (SeNPs) via probiotics. A novel kind of exopolymer-functionalized nanoselenium (SeEPS), whose average size was 67.0 ± 0.6 nm, was produced by Bacillus subtilis SR41, whereas the control consisted of exopolymers without selenium (EPS). Chemical composition analysis, Fourier transform infrared (FTIR) spectroscopy and high-performance liquid chromatography (HPLC) confirmed that SeEPS and EPS shared similar polysaccharide characteristic groups, such as COO- and C=O, and contained not only 45.2–45.4% of sugars but also 23.5–24.7% of proteins and some lipids. Both SeEPS and EPS were primarily composed of mannose, amino glucose, ribose, glucose and galactose. Furthermore, to identify the biologically active component of SeEPS, three kinds of selenium particles with different stabilizers [Se(0), bovine serum albumin-Se and EPS-Se] were synthesized chemically, and their ability to scavenge free radicals in vitro was compared with that of SeEPS and EPS. The results revealed that EPS itself exhibited weak superoxide and hydroxyl radical scavenging abilities. Nevertheless, SeEPS had superior antioxidant properties compared to all other products, possibly due to the specific structure of SeNPs and exopolymers. Our results suggested that exopolymer-functionalized SeNPs with specific monosaccharide composition and structure could eventually find a potential application as an antioxidant.

Selenocoxib-3, a novel anti-inflammatory therapeutic effectively resolves colitis.

Ulcerative colitis (UC) is an idiopathic, chronic and relapsing colonic inflammatory disease. Despite the involvement of diverse intricate mechanisms, COX mediated inflammatory pathway is crucial in the pathophysiology of colitis. Thus, COX inhibition is imperative for managing colitis-associated inflammation. However, the use of COX inhibitory classical non-steroidal anti-inflammatory drugs (NSAIDs) for inflammation resolution has been linked to sudden increased flare-ups. Therefore, considering the anti-inflammatory and pro-resolution effects of antioxidant and essential trace element Selenium (Se), a Seleno-derivative of Celecoxib called Selenocoxib-3 was characterized and evaluated for its favourable pharmacokinetics, safety margins and anti-inflammatory therapeutic potential in DSS-induced experimental colitis. The serum pharmacokinetic profiling [elimination rate constant (K) and clearance (Cl) and toxicity profiling suggested enhanced efficacy, therapeutic potential and lesser toxicity of Selenocoxib-3 as compared to its parent NSAID Celecoxib. In vivo studies demonstrated that Selenocoxib-3 efficiently resolves the gross morphological signs of DSS-induced colitis such as diarrhoea, bloody stools, weight loss and colon shortening. Further, intestinal damage evaluated by H & E staining and MPO activity suggested of histopathological disruptions, such as neutrophil infiltration, mucodepletion and cryptitis, by Selenocoxib-3. The expression profiles of COX-1/2 demonstrated mitigation of pro-inflammatory mediators thereby promoting anti-inflammatory efficacy of Selenocoxib-3 when compared with Celecoxib. The current study suggests translational applicability of Se-containing novel class of COX inhibitors for efficiently managing inflammatory disorders such as UC.

Essential trace element selenium and redox regulation: its metabolism, physiological function, and related diseases

Graphical abstract Abstract The essential trace element selenium plays a significant role in redox homeostasis in the human body. Selenium is very reactive and has a potent toxicity; however, the living body cleverly utilizes its reactivity for redox reactions. The biological function of selenium is mainly mediated by selenoproteins, which contain selenocysteine, a cysteine analogue that possesses selenium instead of sulphur. Twenty-five types of human selenoproteins have been identified, including glutathione peroxidase (GPX; for the reduction of hydrogen peroxide and lipid hydroperoxide) and thioredoxin reductase (for redox regulation). Selenoprotein P (SELENOP), which is a major selenoprotein in the plasma, is mainly synthesized in the liver and secreted into the plasma. As a multifunctional protein with selenium-transporting activity, GPX-like activity, and metal-binding properties, SELENOP plays a vital role in selenium metabolism and redox regulation. This review focuses on the relationship between selenium metabolism and redox regulation, particularly on the physiological role of selenoproteins and the pathophysiological implications of its disorder. Furthermore, the significant roles of selenium in infectious diseases and its utility for phylaxis are discussed.

Comparative Proteomic Analysis Reveals the Effect of Selenoprotein W Deficiency on Oligodendrogenesis in Fear Memory.

The essential trace element selenium plays an important role in maintaining brain function. Selenoprotein W (SELENOW), the smallest selenoprotein that has been identified in mammals, is sensitive to selenium levels and abundantly expressed in the brain. However, its biological role in the brain remains to be clarified. Here, we studied the morphological and functional changes in the brain caused by SELENOW deficiency using its gene knockout (KO) mouse models. Histomorphological alterations of the amygdala and hippocampus, specifically in the female SELENOW KO mice, were observed, ultimately resulting in less anxiety-like behavior and impaired contextual fear memory. Fear conditioning (FC) provokes rapidly intricate responses involving neuroplasticity and oligodendrogenesis. During this process, the females generally show stronger contextual FC than males. To characterize the effect of SELENOW deletion on FC, specifically in the female mice, a Tandem mass tag (TMT)-based comparative proteomic approach was applied. Notably, compared to the wildtype (WT) no shock (NS) mice, the female SELENOW KO NS mice shared lots of common differentially expressed proteins (DEPs) with the WT FC mice in the hippocampus, enriched in the biological process of ensheathment and oligodendrocyte differentiation. Immunostaining and Western blotting analyses further confirmed the proteomic results. Our work may provide a holistic perspective of gender-specific SELENOW function in the brain and highlighted its role in oligodendrogenesis during fear memory.

Humoral immune response to COVID-19 mRNA vaccination in relation to selenium status

The essential trace element selenium (Se) is of central importance for human health and particularly for a regular functioning of the immune system. In the context of the current pandemic, Se deficiency in patients with COVID-19 correlated with disease severity and mortality risk. Selenium has been reported to be associated with the immune response following vaccination, but it is unknown whether this also applies to SARS-CoV-2 vaccines. In this observational study, adult health care workers (n = 126) who received two consecutive anti-SARS-CoV-2 vaccinations by BNT162b2 were followed for up to 24 weeks, with blood samples collected at the first and second dose and at three and 21 weeks after the second dose. Serum SARS-CoV-2 IgG titres, neutralising antibody potency, total Se and selenoprotein P concentrations, and glutathione peroxidase 3 activity were quantified. All three biomarkers of Se status were significantly correlated at all the time points, and participants who reported supplemental Se intake displayed higher Se concentrations. SARS-CoV-2 IgG titres and neutralising potency were highest three weeks after the second dose and decreased towards the last sampling point. The humoral immune response was not related to any of the three Se status biomarkers. Supplemental Se intake had no effect at any time point on the vaccination response as measured by serum SARS-CoV-2 IgG levels or neutralising potency. Overall, no association was found between Se status or supplemental Se intake and humoral immune response to COVID-19 mRNA vaccination.

Natural Autoimmunity to Selenoprotein P Impairs Selenium Transport in Hashimoto's Thyroiditis.

The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto’s thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, p = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, p = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.

Female Mice with Selenocysteine tRNA Deletion in Agrp Neurons Maintain Leptin Sensitivity and Resist Weight Gain While on a High-Fat Diet.

The role of the essential trace element selenium in hypothalamic physiology has begun to come to light over recent years. Selenium is used to synthesize a family of proteins participating in redox reactions called selenoproteins, which contain a selenocysteine residue in place of a cysteine. Past studies have shown that disrupted selenoprotein expression in the hypothalamus can adversely impact energy homeostasis. There is also evidence that selenium supports leptin signaling in the hypothalamus by maintaining proper redox balance. In this study, we generated mice with conditional knockout of the selenocysteine tRNA[Ser]Sec gene (Trsp) in an orexigenic cell population called agouti-related peptide (Agrp)-positive neurons. We found that female TrspAgrpKO mice gain less weight while on a high-fat diet, which occurs due to changes in adipose tissue activity. Female TrspAgrpKO mice also retained hypothalamic sensitivity to leptin administration. Male mice were unaffected, however, highlighting the sexually dimorphic influence of selenium on neurobiology and energy homeostasis. These findings provide novel insight into the role of selenoproteins within a small yet heavily influential population of hypothalamic neurons.