scholarly journals Exposure to Low Dose of Cinnabar (a Naturally Occurring Mercuric Sulfide (HgS)) Caused Neurotoxicological Effects in Offspring Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Chun-Fa Huang ◽  
Chuan-Jen Hsu ◽  
Shing-Hwa Liu ◽  
Shoei-Yn Lin-Shiau
Keyword(s):  
Low Dose ◽  
Developmental Stages ◽  
Fetal Brain ◽  
Severe Injuries ◽  
Mercuric Sulfide ◽  
Naturally Occurring ◽  
Neurotoxic Effects ◽  
Irreversible Effects ◽  
Hg Accumulation ◽  
Developing Mice

Cinnabar, a naturally occurring mercuric sulfide (HgS), has long been used in Chinese mineral medicine for more than 2000 years. Although mercury is well-known for its toxicity, whether cinnabar induces neurotoxicity, especially in infants and children, is unknown. The purpose of this study was to explore the neurotoxic effects of low-dose of cinnabar (10 mg/kg/day) on developing mice. The results revealed neurobehavioral defects in F1-C-Cin group, which were associated with Hg accumulation, increased NOxlevels in whole blood, and Na+/K+-ATPase activities in brain tissues. F1- and F2-Cin-V groups were found to increase brain Hg contents and prominent neurobehavioral defects compared with F1-C-V group, suggesting that the fetal brain was more susceptible to irreversible effects for cinnabar-induced damage. Moreover, F1- and F2-Cin-Cin groups had severely neurobehavioral dysfunctions, closely correlated with the further alteration of NOxlevels and Na+/K+-ATPase activities than F1- and F2-C-Cin groups. Effects in F2-Cin-Cin group were more significant than those in F1-Cin-Cin group. In conclusion, this study demonstrates that exposure to low-dose of cinnabar during the perinatal and developmental stages results in irreversible and severe injuries of the neurotoxicity in offspring, and NOxand Na+/K+-ATPase activities may exist potential and useful biomarkers for neurotoxicity-induced by low-doses of mercuric compounds.

Neurotoxic Effects of Gestational Administration of Low-dose Lead Acetate

1996 ◽  
Vol 16 (5) ◽  
pp. 431-436 ◽  
Author(s):  
M. Teresa Antonio ◽  
Sara Martínez ◽  
M. Luisa Leret ◽  
Isabel Corpas
Keyword(s):  
Lead Acetate ◽  
Low Dose ◽  
Neurotoxic Effects

scholarly journals Thyroid hormones and fetal neurological development

2011 ◽  
Vol 209 (1) ◽  
pp. 1-8 ◽  
Author(s):  
J Patel ◽  
K Landers ◽  
H Li ◽  
R H Mortimer ◽  
K Richard
Keyword(s):  
Thyroid Hormone ◽  
Cell Membrane ◽  
Hormone Receptors ◽  
Developmental Stages ◽  
Fetal Brain ◽  
Neurological Development ◽  
Thyroid Hormone Metabolism ◽  
Pituitary Thyroid Axis ◽  
Fetal Thyroid ◽  
Type 3

The development of fetal thyroid function is dependent on the embryogenesis, differentiation, and maturation of the thyroid gland. This is coupled with evolution of the hypothalamic–pituitary–thyroid axis and thyroid hormone metabolism, resulting in the regulation of thyroid hormone action, production, and secretion. Throughout gestation there is a steady supply of maternal thyroxine (T4) which has been observed in embryonic circulation as early as 4 weeks post-implantation. This is essential for normal early fetal neurogenesis. Triiodothyronine concentrations remain very low during gestation due to metabolism via placental and fetal deiodinase type 3. T4 concentrations are highly regulated to maintain low concentrations, essential for protecting the fetus and reaching key neurological sites such as the cerebral cortex at specific developmental stages. There are many known cell membrane thyroid hormone transporters in fetal brain that play an essential role in regulating thyroid hormone concentrations in key structures. They also provide the route for intracellular thyroid hormone interaction with associated thyroid hormone receptors, which activate their action. There is a growing body of experimental evidence from rats and humans to suggest that even mild maternal hypothyroxinemia may lead to abnormalities in fetal neurological development. Our review will focus on the ontogeny of thyroid hormone in fetal development, with a focus on cell membrane transporters and TR action in the brain.

scholarly journals Acetyl-CoA:4-Hydroxybutinylbithiophene O-Acetyltransferase Isoenzymes from Tagetes patula Seedlings

1987 ◽  
Vol 42 (7-8) ◽  
pp. 885-890 ◽  
Author(s):  
Gernot Metschulat ◽  
Rainer Sütfeld
Keyword(s):  
Coenzyme A ◽  
Developmental Stages ◽  
Complete Separation ◽  
Tagetes Patula ◽  
Acetyl Coa ◽  
Ph Optimum ◽  
Acyltransferase Activity ◽  
Enzyme Preparations ◽  
Naturally Occurring ◽  
Acyl Coenzyme A

Naturally-occurring hydroxybutinylbithiophene derivatives were acylated by enzyme preparations of Tagetes patula seedlings in the presence of distinct acyl-Coenzyme A esters. The O-acyltransferase activity could only be detected after almost complete separation of the enzyme from counter-currently acting esterases which were present in the same extracts. This was achieved by affinity chromatography on Cibachron Blue A. During this procedure, the O-acyl-transferase was split, yielding two active fractions. Both had a Mr of 37,000 (±5,000), equal isoelectric properties, a pH optimum of pH 7.0, and were considerably inhibited in the presence of free Coenzyme A. Small differences existed in their affinities for their thiophenic substrates (3,4-dihydroxybutinylbithiophene and 4-hydroxybutinylbithiophene, respectively), as well as for various acyl-CoA esters as cosubstrates. With the preferred cosubstrate, acetyl-CoA, acylation took place at the 4-position of the butinyl side chain of the molecules, forming the naturally- occurring 4-acetoxybutinylbithiophene and 3-OH,4-OAc-butinylbithiophene, respectively. From the other acyl-CoA esters employed, only propionyl-CoA was likewise converted, forming the corresponding O-propionyl esters. The reactions observed are suggested to be catalyzed by two acetyl-CoA: 4-hydroxybutinylbithiophene O-acetyltransferase isoenzymes which exhibit different affinities for particular substrates and cosubstrates. The activities of both the isoenzymes changed drastically if plant material from different developmental stages was used as enzyme source. Therefore, it may be suggested that these isoenzymes play an important regulatory role in the metabolism of naturally-occurring hydroxy- and acetoxybutinylbithiophenes and their derivatives.

scholarly journals Epigenomic programming in early fetal brain development

Epigenomics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1053-1070
Author(s):  
Luolan Li ◽  
Cecile L Maire ◽  
Misha Bilenky ◽  
Annaïck Carles ◽  
Alireza Heravi-Moussavi ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Neural Progenitor Cells ◽  
Developmental Stages ◽  
Fetal Brain ◽  
Brain Regions ◽  
Ganglionic Eminence ◽  
Fetal Brain Development ◽  
Gestational Week ◽  
Normal Human ◽  
Comprehensive Reference

Aim: To provide a comprehensive understanding of gene regulatory networks in the developing human brain and a foundation for interpreting pathogenic deregulation. Materials & methods: We generated reference epigenomes and transcriptomes of dissected brain regions and primary neural progenitor cells (NPCs) derived from cortical and ganglionic eminence tissues of four normal human fetuses. Results: Integration of these data across developmental stages revealed a directional increase in active regulatory states, transcription factor activities and gene transcription with developmental stage. Consistent with differences in their biology, NPCs derived from cortical and ganglionic eminence regions contained common, region specific, and gestational week specific regulatory states. Conclusion: We provide a high-resolution regulatory network for NPCs from different brain regions as a comprehensive reference for future studies.

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

2008 ◽  
Vol 232 (9) ◽  
pp. 1321-1328 ◽  
Author(s):  
Matthew A. Vaughan ◽  
Edward C. Feldman ◽  
Bruce R. Hoar ◽  
Richard W. Nelson
Keyword(s):  
Low Dose ◽  
Naturally Occurring

Pooling of Laying Hen Environmental Swabs and Efficacy of Salmonella Detection

2020 ◽  
Vol 83 (6) ◽  
pp. 943-950
Author(s):  
DEANA R. JONES ◽  
RICHARD K. GAST ◽  
PRAFULLA REGMI ◽  
GARRETT E. WARD ◽  
KENNETH E. ANDERSON ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Salmonella Enteritidis ◽  
Low Dose ◽  
High Dose ◽  
Environmental Testing ◽  
Naturally Occurring ◽  
Rate Of Recovery ◽  
High Doses ◽  
The U.S ◽  
Salmonella Heidelberg

ABSTRACT Environmental testing for Salmonella Enteritidis is required for U.S. shell egg producers with ≥3,000 hens on a farm. The egg producer assumes all costs for the mandatory testing. According to the U.S. Food and Drug Administration (FDA) Egg Rule, either manure scraper or drag swabs can be collected according to published guidelines and requirements. The present study was undertaken to determine the efficacy of Salmonella detection with one-, two-, and four-swab pools of either manure scraper or drag swabs. Resistant isolates of Salmonella serovars Enteritidis (1,000 ppm of streptomycin), Heidelberg (200 ppm of nalidixic acid [NA]), Typhimurium (200 ppm of NA), and Kentucky (200 ppm of NA) were utilized. Low (approximately 8.4 CFU) and high (approximately 84 CFU) levels of inocula were introduced onto a single swab within a pool. Single flocks from each conventional cage (manure scraper swabs) and cage-free barn (drag swabs) were monitored throughout the study at the ages required under the FDA Egg Rule. The highest and most consistent recovery of inoculum was found in single swab samples. For low dose inocula, recovery of isolates was low from single manure scraper swabs (57.9 to 29.2%) and decreased as more swabs were added to the pool. Recovery of isolates from manure scraper swabs was higher for high dose inocula, although Salmonella Heidelberg was outcompeted by the naturally occurring flora and had the lowest rate of recovery among the isolates tested. One- and two-swab pools of drag swabs had similar rates of recovery at both low and high doses for Salmonella Enteritidis, Salmonella Heidelberg, and Salmonella Typhimurium. When Salmonella Enteritidis and Salmonella Kentucky were combined in an inoculum, Salmonella Enteritidis was recovered at a much higher rate than was Salmonella Kentucky for all types of swabs and doses of inocula. Pooling of two drag swabs allowed for similar detection of low and high dose Salmonella, but the pooling of manure scraper swabs decreased detection of low dose Salmonella. HIGHLIGHTS

scholarly journals Spatiotemporal 7q11.23 Protein Network Implicates the GTF2I-PRKDC-DDR Pathway During Early-Fetal Brain Development in Psychiatric Diseases

2020 ◽  
Author(s):  
Guan Ning Lin ◽  
Liang Chen ◽  
Weidi Wang ◽  
Wenxiang Cai ◽  
Weichen Song ◽  
...  
Keyword(s):  
Brain Development ◽  
Developmental Stages ◽  
Copy Number Variants ◽  
Fetal Brain ◽  
Brain Regions ◽  
Driver Gene ◽  
Physical Interaction ◽  
Psychiatric Diseases ◽  
Protein Protein Interaction ◽  
Ppi Networks

Abstract Background: Recurrent deletions and duplications of chromosome 7q11.23 copy number variants (CNVs) are associated with several psychiatric disorders. Previous works showed GTF2I associated with Williams-Beuren syndrome, but pathways affected by GTF2I are poorly defined. Although phenotypic abnormalities have been observed in patients and animal models, the targeted human brain regions, developmental stages, protein networks, and signaling pathways, influenced by this CNV remain unclear. Results: Topological changes were observed in protein-protein interaction (PPI) networks throughout different stages of brain development. Early and late fetal periods of development in the cortex, striatum, hippocampus, and amygdale were observed as the vital periods and regions for 7q11.23 CNV proteins. As a driver gene, GTF2I interacted with PRKDC and BRCA1 to involve in DNA Damaging Response (DDR) pathway. The physical interaction between GTF2I with PRKDC was confirmed experimentally by the liquid chromatography-tandem mass spectrometry (LC-MS/MS). Conclusion: We identified that striatum, hippocampus, and amygdala are crucial regions for establishing connectivity between 7q11.23 proteins and their partners in early and late fetal periods. Our results suggested that GTF2I-PRKDC-DDR and GTF2I-BRCA1-DDR pathway is crucial for the 7q11.23 CNV genes to contribute to the pathogenesis of psychiatric diseases.

scholarly journals Myonuclear content regulates cell size with similar scaling properties in mice and humans

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenth-Arne Hansson ◽  
Einar Eftestøl ◽  
Jo C. Bruusgaard ◽  
Inga Juvkam ◽  
Alyssa W. Cramer ◽  
...  
Keyword(s):  
Cell Size ◽  
Developmental Stages ◽  
Scaling Law ◽  
Muscle Fibers ◽  
The Body ◽  
Experimental Conditions ◽  
Scaling Properties ◽  
Nuclear Number ◽  
The Relationship ◽  
Developing Mice

AbstractMuscle fibers are the largest cells in the body, and one of its few syncytia. Individual cell sizes are variable and adaptable, but what governs cell size has been unclear. We find that muscle fibers are DNA scarce compared to other cells, and that the nuclear number (N) adheres to the relationship N = aVb where V is the cytoplasmic volume. N invariably scales sublinearly to V (b < 1), making larger cells even more DNA scarce. N scales linearly to cell surface in adult humans, in adult and developing mice, and in mice with genetically reduced N, but in the latter the relationship eventually fails when they reach adulthood with extremely large myonuclear domains. Another exception is denervation-atrophy where nuclei are not eliminated. In conclusion, scaling exponents are remarkably similar across species, developmental stages and experimental conditions, suggesting an underlying scaling law where DNA-content functions as a limiter of muscle cell size.

scholarly journals Maternal Dietary Exposure to Low-Dose Bisphenol A Affects Metabolic and Signaling Pathways in the Brain of Rat Fetuses

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1448
Author(s):  
Claudia Tonini ◽  
Marco Segatto ◽  
Simone Gagliardi ◽  
Simona Bertoli ◽  
Alessandro Leone ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Low Dose ◽  
Fetal Brain ◽  
Dietary Exposure ◽  
Estrogen Receptor Α ◽  
Protein Prenylation ◽  
Synthetic Compound ◽  
Mva Pathway ◽  
And Function ◽  
The Brain

Bisphenol A (BPA) is a synthetic compound widely used for the production of polycarbonate plasticware and epoxy resins. BPA exposure is widespread and more than 90% of individuals have detectable amounts of the molecule in their body fluids, which originates primarily from diet. Here, we investigated whether prenatal exposure to BPA affects the mevalonate (MVA) pathway in rat brain fetuses, and whether potential effects are sex-dependent. The MVA pathway is important for brain development and function. Our results demonstrate that the fetal brain, exposed in utero to a very low dose of BPA (2.5 µg/kg/day), displayed altered MVA pathway activation, increased protein prenylation, and a decreased level of pro-BDNF. Interestingly, the BPA-induced effects on estrogen receptor α were sex-dependent. In conclusion, this work demonstrates intergenerational effects of BPA on the brain at very low doses. Our results reveal new targets for BPA-induced interference and underline the impacts of BPA on health.

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