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Sex- and population-specific hormetic responses to increasing dietary selenium in zebrafish (Danio rerio)

ABSTRACT: We tested the hypothesis that the behavioral response to selenium (Se) follows a hormetic dose response pattern, manifested through the functions of selenoproteins within the brain. We measured anxiety-related behaviors in zebrafish (Danio rerio) at deficient, control and supplemented levels of dietary Se, and measured the transcriptional response of selenoprotein genes important for neuroprotection. We also used a microarray approach to assess the transcriptomic response of the midbrain to Se. The behavioral response to Se was characterized by hormesis, and the direction, magnitude, and shape of the hormetic responses were dependent on both sex and zebrafish population. Transcription of selenoproteins within the midbrain also responded to Se in a similar hormetic dose-dependent manner, with sex and population influencing the trajectory of the responses. The hormetic behavioral response to Se may therefore be manifested through selenoproteins in the brain, but the influence is not direct. We performed a microarray analysis comparing the midbrain-specific transcriptome between male zebrafish from two populations (Pargana: P and Transgenic Mosaic 1: T) fed either a control, Se deficient, or Se supplemented diet (17 total samples: 9 fish per population, 3 fish per diet: missing 1 P control sample).

ORGANISM(S): Danio rerio

SUBMITTER: Maia Benner

PROVIDER: E-GEOD-52484 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Sex- and population-specific hormetic responses to increasing dietary selenium in zebrafish (Danio rerio)

Project description:We tested the hypothesis that the behavioral response to selenium (Se) follows a hormetic dose response pattern, manifested through the functions of selenoproteins within the brain. We measured anxiety-related behaviors in zebrafish (Danio rerio) at deficient, control and supplemented levels of dietary Se, and measured the transcriptional response of selenoprotein genes important for neuroprotection. We also used a microarray approach to assess the transcriptomic response of the midbrain to Se. The behavioral response to Se was characterized by hormesis, and the direction, magnitude, and shape of the hormetic responses were dependent on both sex and zebrafish population. Transcription of selenoproteins within the midbrain also responded to Se in a similar hormetic dose-dependent manner, with sex and population influencing the trajectory of the responses. The hormetic behavioral response to Se may therefore be manifested through selenoproteins in the brain, but the influence is not direct.

2014-05-01 | GSE52484 | GEO

Transcriptomic comparison between brain regions of behaviorally distinct wild and domesticated zebrafish (Danio rerio) populations

Project description:Zebrafish populations recently collected from the wild differ from domesticated populations in anxiety-related behaviors. We measured anxiety-related behaviors in wild and domesticated zebrafish populations and performed a multi-brain region transcriptional comparison using microarrays to try to understand the genetic changes that accompany behavioral adaptation to domestication. We performed a microarray analysis comparing the midbrain and telencephalon brain regions of male and female adult zebrafish from four populations varying in domestication history (Wild: Nadia (N) and Pargana (P), and Domesticated: Scientific Hatchery (S) and Transgenic Mosaic 1 (T)). We collected 16 samples per brain region (4 samples per zebrafish population, with 1 telencephalon sample missing for the S population). We attempted to maintain equal sex ratios within each zebrafish population, but this was not always possible due to sex biases within some populations.

2014-03-01 | E-GEOD-52512 | biostudies-arrayexpress

Metabolic control of inflammation by selenium

Project description:Trace element selenium (Se) is incorporated as the 21st amino acid, selenocysteine (Sec), into selenoproteins through tRNA[Ser]Sec. Selenoproteins act as gatekeepers of redox homeostasis and modulate immune function to effect anti-inflammation and resolution. However, mechanistic underpinnings involving metabolic reprogramming during inflammation and resolution remain poorly understood. Endotoxin lipopolysaccharide (LPS) activation of murine bone marrow-derived macrophages (BMDMs) cultured in the presence or absence of Se (as selenite) was used to examine temporal changes in the proteome and metabolome by multiplexed tandem mass tag-quantitative proteomics, metabolomics, and machine-learning approaches. Se-dependent modulation of glycolytic, TCA and PPP pathways predisposed BMDMs to preferentially increase OXPHOS to efficiently regulate inflammation and its timely resolution. Use of macrophages lacking selenoproteins, indicated that all three metabolic nodes were sensitive to selenoproteome expression. Furthermore, inhibition of SDH with dimethylmalonate affected the pro-resolving effects of Se by increasing the resolution interval in a murine peritonitis model.

2021-02-09 | PXD023005 | Pride

SELENOK-Dependent CD36 Palmitoylation Regulates Microglial Functions and Aβ Phagocytosis

Project description:Amyloid-beta (Aβ) is a key factor in the onset and progression of Alzheimer's disease (AD). Selenium (Se) compounds show promise in AD treatment. Here, we reveal that selenoprotein K (SELENOK), a selenoprotein involved in immune regulation and potentially related to AD pathology, plays a critical role in microglial immune response, migration, and phagocytosis. In vivo and in vitro studies corroborate that SELENOK deficiency inhibits microglial Aβ phagocytosis, exacerbating cognitive deficits in 5xFAD mice, which are reversed by SELENOK overexpression. Mechanistically, SELENOK is involved in CD36 palmitoylation through DHHC6, regulating CD36 localization to microglial plasma membranes and thus impacting Aβ phagocytosis. CD36 palmitoylation is reduced in the brains of AD patients and mice. Se supplementation promotes SELENOK expression and CD36 palmitoylation, enhancing microglial Aβ phagocytosis and mitigating AD progression. We have identified the regulatory mechanisms from Se-dependent selenoproteins to Aβ pathology, providing novel insights into potential therapeutic strategies involving Se and selenoproteins.

2024-02-29 | GSE255034 | GEO

Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents

Project description:Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1), are down-regulated dramatically by selenium (Se) deficiency. Selenoprotein levels in rats increase sigmoidally with increasing dietary Se and reach defined plateaus at the Se requirement, making them sensitive biomarkers for Se deficiency, but not high for Se status. Biomarkers for high Se status are needed as super-nutritional Se intakes are associated with beneficial and adverse health outcomes, but conventional biomarkers are not especially useful above the Se requirement. To characterize Se regulation of the transcriptome, we conducted 3 microarray experiments in weanling mice and rats fed Se-deficient diets supplemented with levels of Se up to 5 µg Se/g diet.

2011-01-19 | GSE23895 | GEO

Elevated dairy fat intake in lactating women alters milk lipid and fatty acids without detectible changes in expression of genes related to lipid uptake or synthesis

Project description:Previous work has demonstrated that elevated maternal lipid intake (particularly from dairy products) is associated with increased lipids and altered fatty acid profile in milk produced by healthy lactating women. We investigate our primary hypothesis that a maternal diet rich in full-fat dairy products would simultaneously increase milk lipid percent and expression of genes related to the uptake and/or de novo biosynthesis of milk lipids. Within a a randomized, crossover study we performed a microarray analysis comparing 6 lactating women with diets rich in full-fat or non-fat dairy products. Each woman consumed one of the two diets during timepoint one, and after a two week washout period, switched over to the other diet. The timepoint value indicates whether the particular dietary treatment was consumed first or second.

2015-02-24 | E-GEOD-66191 | biostudies-arrayexpress

Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents

2011-01-19 | E-GEOD-23895 | biostudies-arrayexpress

Shigella flexneri ntrBC and nac mutant expression analysis

Project description:Investigate whole genome gene expression level changes in an S. flexneri ntrBC and nac mutants compared to wild type strain. NtrBC is a two component regulatory system, nac is a transcriptional activator Mutations in ntrBC and nac result in small plaque formation in Henle cell monolayers compared to wild type bacteria. Gene expression studies were pursued to identify the genes regulated by these transcriptional regulators. A 9 array study using total RNA recovered from the wild type, ntrBC and nac mutant strains in three independent experiments. Bacterial RNA was isolated from infected Henle cells at four hours post-infection. Gene expression from the mutant strains was compared to that of wild type.

2014-05-09 | E-GEOD-49939 | biostudies-arrayexpress

Wild type mice (Trsp) vs Trsp-knockout mice (DTrsp) or A34 or G37L or G37H transgenic mice

Project description:Comparative analysis of gene expression in the liver of the Trsp-knockout mice (Trspfl/fl-AlbCre+/+) and A34 (Trspfl/fl-AlbCre+/+-A34t/t), G37L (Trspfl/fl-AlbCre+/+-G37t/t; 2 copies), G37H (Trspfl/fl-AlbCre+/+-G37t/t; 16 copies) transgenic mice with gene expression of wild type mice (Trsp+/+-AlbCre+/+). Sec (selenocysteine) is biosynthesized on its tRNA and incorporated into selenium-containing proteins (selenoproteins) as the 21st amino acid residue. Selenoprotein synthesis is dependent on Sec tRNA and the expression of this class of proteins can be modulated by altering Sec tRNA expression. The gene encoding Sec tRNA (Trsp) is a single-copy gene and its targeted removal in liver demonstrated that selenoproteins are essential for proper function wherein their absence leads to necrosis and hepatocellular degeneration. In the present study, we found that the complete loss of selenoproteins in liver was compensated for by an enhanced expression of several phase II response genes and their corresponding gene products. The replacement of selenoprotein synthesis in mice carrying mutant Trsp transgenes, wherein housekeeping, but not stress-related selenoproteins are expressed, led to normal expression of phase II response genes. Thus the present study provides evidence for a functional link between housekeeping selenoproteins and phase II enzymes. Trsp vs DTrsp; Trsp vs A34; Trsp vs G37L; Trsp vs G37H. Biological replicates from littermates. One replicate per array.

2010-05-25 | E-GEOD-12495 | biostudies-arrayexpress

Substrate-specific gene expression in the amphibian chytrid pathogen

Project description:Determining the mechanisms of host-pathogen interaction is critical for understanding and mitigating infectious disease. Mechanisms of fungal pathogenicity are of particular interest given the recent outbreaks of fungal diseases in wildlife populations. Our study focuses on Batrachochytrium dendrobatidis (Bd), the chytrid pathogen responsible for amphibian declines around the world. Previous studies have hypothesized a role for several specific families of secreted proteases as pathogenicity factors in Bd, but the expression of these genes has only been evaluated in laboratory growth conditions. Here we conduct a genome-wide study of Bd gene expression under two different nutrient conditions. We compare Bd gene expression profiles in laboratory growth media and in host tissue (i.e., frog skin). A large proportion of genes in the Bd genome show increased expression when grown in host tissue, indicating the importance of studying pathogens in their infection environment. A number of gene classes show particularly high levels of expression in host tissue, including three families of secreted proteases (metallo-, serine- and aspartyl-proteases), adhesion genes, lipase-3 encoding genes, and a group of phylogenetically unusual crinkler-like effectors. We discuss the roles of these different genes as putative pathogenicity factors and discuss what they can teach us about Bd's metabolic targets, host invasion, and pathogenesis. One 12-plex chip was analyzed from 12 RNA samples extracted from Batrachochytrium dendrobatidis grown in 2 substrates. Six biological replicates were used for each substrate - sterile frog skin and tryptone nutrient broth. The same dye, Cy5, was used for all samples.

2012-11-01 | E-GEOD-37135 | biostudies-arrayexpress

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