Neurotoxicology and teratology最新文献

{"title":"Exposure to the pharmaceutical buspirone alters locomotor activity, anxiety-related behaviors, and transcripts related to serotonin signaling in larval zebrafish (Danio rerio)","authors":"Angel Biju ,&nbsp;Emma Ivantsova ,&nbsp;Christopher L. Souders II ,&nbsp;Cole English ,&nbsp;Lev Avidan ,&nbsp;Christopher J. Martyniuk","doi":"10.1016/j.ntt.2023.107318","DOIUrl":"10.1016/j.ntt.2023.107318","url":null,"abstract":"<div><p><span><span>Buspirone is a pharmaceutical used to treat general anxiety disorder by acting on the </span>dopaminergic<span><span> and serotoninergic system. Buspirone, like many human pharmaceuticals, has been detected in municipal wastewater; however, the environmental exposure risks are unknown for this psychoactive compound. We studied the effects of buspirone on the </span>behavior<span> of zebrafish, focusing on locomotor and anxiolytic behavior. We also measured transcripts associated with oxidative stress<span>, neurotoxicity, and serotonin signaling to identify potential mechanisms underlying the behavioral changes. Concentrations ranged from environmentally relevant (nM) to physiologically active concentrations typical of human pharmaceuticals (μM). Buspirone treatment did not impact survival, nor did it induce deformities in zebrafish treated for 7 days up to 10 μM. There was a positive relationship between locomotor activity and buspirone concentration in dark periods of the visual motor response test. In the light-dark preference test, both the average time per visit to the dark zone and the percent cumulative duration in the dark zone were increased by 1 μM buspirone. Transcript levels of </span></span></span></span><em>ache</em>, <em>manf</em>, and <em>mbp</em> were decreased in larvae, while the expression of <em>gap43</em> was increased following exposure to buspirone, indicating potential neurotoxic effects. There was also reduced expression of serotonin-related genes encoding receptors, transporters, and biosynthesis enzymes (i.e., <em>5ht1aa</em>, <em>sertb</em>, and <em>tph1a</em>). These data increase understanding of the behavioral and molecular responses in zebrafish following waterborne exposure to neuroactive pharmaceuticals like buspirone.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"101 ","pages":"Article 107318"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental exposure to methylmercury alters GAD67 immunoreactivity and morphology of endothelial cells and capillaries of midbrain and hindbrain regions of adult rat offspring","authors":"Nazneen Y. Rustom,&nbsp;James N Reynolds","doi":"10.1016/j.ntt.2024.107320","DOIUrl":"10.1016/j.ntt.2024.107320","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Methylmercury (MeHg) is an environmental contaminant that is of particular concern in Northern Arctic Canadian populations. Specifically, organic mercury compounds such as MeHg are potent toxicants that affect multiple bodily systems including the nervous system. Developmental exposure to MeHg is a major concern, as the developing fetus and neonate are thought to be especially vulnerable to the toxic effects of MeHg. The objective of this study was to examine developmental exposure to low doses of MeHg and effects upon the adult central nervous system (CNS). The doses of MeHg chosen were scaled to be proportional to the concentrations of MeHg that have been reported in human maternal blood samples in Northern Arctic Canadian populations.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;p&gt;Offspring were exposed to MeHg maternally where pregnant Sprague Dawley rats were fed cookies that contained MeHg or vehicle (vehicle corn oil; MeHg 0.02 mg/kg/body weight or 2.0 mg/kg/body weight) daily, throughout gestation (21 days) and lactation (21 days). Offspring were not exposed to MeHg after the lactation period and were euthanized on postnatal day 450. Brains were extracted, fixed, frozen, and sectioned for immunohistochemical analysis. A battery of markers of brain structure and function were selected including neuronal GABAergic enzymatic marker glutamic acid decarboxylase-67 (GAD67), apoptotic/necrotic marker cleaved caspase-3 (CC3), catecholamine marker tyrosine hydroxylase (TH), immune inflammatory marker microglia (Cd11b), endothelial cell marker rat endothelial cell antigen-1 (RECA-1), doublecortin (DCX), Bergmann glia (glial fibrillary acidic protein (GFAP)), and general nucleic acid and cellular stains Hoechst, and cresyl violet, respectively. Oxidative stress marker lipofuscin (autofluorescence) was also assessed. Both male and female offspring were included in analysis. Two-way analysis of variance (ANOVA) was utilized where sex and treatment were considered as between-subject factors (&lt;em&gt;p&lt;/em&gt;* &lt;0.05). ImageJ was used to assess immunohistochemical results.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;In comparison with controls, adult rat offspring exposed to both doses of MeHg were observed to have (1) increased GAD67 in the cerebellum; (2) decreased lipofuscin in the locus coeruleus; and (3) decreased GAD67 in the anterior CA1 region. Furthermore, in the substantia nigra and periaqueductal gray, adult male offspring consistently had a larger endothelial cell and capillary perimeter in comparison to females. The maternal high dose of MeHg influenced RECA-1 immunoreactivity in both the substantia nigra and periaqueductal gray of adult rat offspring, where the latter neuronal region also showed statistically significant decreases in RECA-1 immunoreactivity at the maternal low dose exposure level. Lastly, males exposed to high doses of MeHg during development exhibited a statistically significant increase in the perimeter of endothelial cel","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"101 ","pages":"Article 107320"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0892036224000023/pdfft?md5=c7f78c6ea199586c09f25fbb6bf7a524&pid=1-s2.0-S0892036224000023-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139397168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amniotic fluid cortisol predicts neonatal and infant development in non-stressed rhesus monkeys: Implications for prenatal stress","authors":"Jeremy Otridge ,&nbsp;Jerrold S. Meyer ,&nbsp;Amanda M. Dettmer","doi":"10.1016/j.ntt.2023.107308","DOIUrl":"10.1016/j.ntt.2023.107308","url":null,"abstract":"<div><p><span>Prenatal stress<span><span><span> adversely affects offspring<span> development, with fetal cortisol (CORT) exposure being a primary hypothesized mechanism for stress-induced developmental deficits. Fetal CORT exposure can be assessed via measurements in </span></span>amniotic fluid. However, in humans, </span>amniocentesis is typically only performed for clinical reasons such as karyotyping; thus, amniotic fluid CORT cannot be obtained from a random sample. To test the hypothesis that fetal CORT exposure predicts neonatal and infant development in healthy primates, we measured amniotic fluid CORT in </span></span><em>N</em><span> = 18 healthy rhesus macaque (</span><em>Macaca mulatta</em>) dams (50:50 female:male infants) between 80 and 124 days gestation (mean ± SEM = 98.3 ± 2.9 days out of 165 days gestational length; i.e., second trimester). Maternal hair cortisol concentrations (HCCs) were assessed throughout pregnancy and lactation. Offspring were assessed for physical growth, neurological development, cognitive development, and HCCs across postnatal days 30–180. Controlling for gestational age at amniocentesis, higher amniotic fluid CORT significantly predicted slower infant growth rate (g/day) in the first 30 days (β = −0.19; R² = 0.71, <em>p</em><span> = .008), poorer sensorimotor scores on the day 30 neonatal assessment (β = −0.28; R</span>² = 0.76, <em>p</em> = .015), and longer time to complete training (β = 0.48; R² = 0.54, <em>p</em> = .026), but better performance (β = 0.91; R² = 0.60, <em>p</em><span> = .011) on a discrimination cognitive task at 120–180 days. Amniotic fluid CORT was not associated with maternal or infant HCCs. Although these results are correlative, they raise the intriguing possibility that fetal CORT exposure in non-stress-exposed primates, as measured by amniotic fluid CORT, programs multiple aspects of neonatal and infant development. On the other hand, amniotic fluid CORT may not relate to chronic CORT levels in either mothers or infants when assessed by hair sampling.</span></p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"100 ","pages":"Article 107308"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61564293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life manganese exposure during multiple developmental periods and adolescent verbal learning and memory","authors":"Alexa Friedman ,&nbsp;Samantha Schildroth ,&nbsp;Julia A. Bauer ,&nbsp;Brent A. Coull ,&nbsp;Donald R. Smith ,&nbsp;Donatella Placidi ,&nbsp;Giuseppa Cagna ,&nbsp;Maxine H. Krengel ,&nbsp;Yorghos Tripodis ,&nbsp;Roberta F. White ,&nbsp;Roberto G. Lucchini ,&nbsp;Robert O. Wright ,&nbsp;Megan Horton ,&nbsp;Christine Austin ,&nbsp;Manish Arora ,&nbsp;Birgit Claus Henn","doi":"10.1016/j.ntt.2023.107307","DOIUrl":"10.1016/j.ntt.2023.107307","url":null,"abstract":"<div><h3>Background</h3><p>Manganese (Mn) is both an essential and toxic metal, and associations with neurodevelopment depend on exposure timing. Prospective data examining early life Mn with adolescent cognition are sparse.</p></div><div><h3>Methods</h3><p>We enrolled 140 Italian adolescents (10–14 years old) from the Public Health Impact of Metals Exposure study. Mn in deciduous teeth was measured using laser ablation-mass spectrometry to represent prenatal, postnatal and early childhood exposure. The California Verbal Learning Test for Children (CVLT-C) was administered to assess adolescent verbal learning and memory. Multivariable regression models estimated changes in CVLT-C scores and the odds of making an error per doubling in dentine Mn in each exposure period. Multiple informant models tested for differences in associations across exposure periods.</p></div><div><h3>Results</h3><p>A doubling in prenatal dentine Mn levels was associated with lower odds of making an intrusion error (OR = 0.23 [95% CI: 0.09, 0.61]). This beneficial association was not observed in other exposure periods. A doubling in childhood Mn was beneficially associated with short delay free recall: (ß = 0.47 [95% CI: −0.02, 0.97]), which was stronger in males (ß = 0.94 [95% CI: 0.05, 1.82]). Associations were null in the postnatal period.</p></div><div><h3>Conclusion</h3><p>Exposure timing is critical for understanding Mn-associated changes in cognitive function.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"100 ","pages":"Article 107307"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41207130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teratogenic impacts of Antiepileptic drugs on development, behavior and reproduction in Drosophila melanogaster","authors":"Shamapari R.,&nbsp;Nagaraj K.","doi":"10.1016/j.ntt.2023.107305","DOIUrl":"10.1016/j.ntt.2023.107305","url":null,"abstract":"<div><p><span><span>Clobazam<span> (CLB) and Vigabatrin (VGB) are the two widely used </span></span>Antiepileptic drugs, which may have teratogenic potentiality and it has been evaluated in the fruit fly </span><span><em>Drosophila melanogaster</em></span>. These different concentrations of CLB (0.156, 0.25, and 0.312 μg/ml) and VGB (17.6, 22, and 44 μg/ml) were used to evaluate the life–history parameters, developmental, and behavioral abnormalities. The results revealed that life-history parameters (fecundity, fertility, larval and pupal mortality) were significantly affected along with varied developmental duration, and pupal and adult deformities in flies on exposure of CLB and VGB in concentration dependent manner. The present study demonstrated that the prenatal treatment of CLB and VGB has displayed clear teratogenic potentiality with various deformities in the fruit fly. The findings could be correlated with the various abnormalities in human caused by the use of AEDs.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"100 ","pages":"Article 107305"},"PeriodicalIF":2.9,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PFOS-induced dyslipidemia and impaired cholinergic neurotransmission in developing zebrafish: Insight into its mechanisms","authors":"Archisman Mahapatra ,&nbsp;Priya Gupta ,&nbsp;Anjali Suman,&nbsp;Shubhendu Shekhar Ray,&nbsp;Rahul Kumar Singh","doi":"10.1016/j.ntt.2023.107304","DOIUrl":"10.1016/j.ntt.2023.107304","url":null,"abstract":"<div><p><span>Perfluorooctane sulfonate<span><span><span> (PFOS) is a persistent organic pollutant that has been widely detected in the environment and is known to accumulate in organisms, including humans. The study investigated dose-dependent mortality, hatching rates, malformations, lipid accumulation, </span>lipid metabolism alterations, and impacts on </span>cholinergic<span> neurotransmission. Increasing PFOS concentration led to higher mortality, hindered hatching, and caused concentration-dependent malformations, indicating severe abnormalities in developing zebrafish. The results also demonstrated that PFOS exposure led to a significant increase in total lipids, triglycerides<span>, total cholesterol, and LDL in a concentration-dependent manner, while HDL cholesterol levels were significantly decreased. Additionally, PFOS exposure led to a significant decrease in glucose levels. The study identified TGs, TCHO, and glucose as the most sensitive biomarkers in assessing lipid metabolism alterations. The study also revealed altered expression of genes involved in lipid metabolism, including upregulation of </span></span></span></span><em>fasn, acaca</em>, and <em>hmgcr</em> and downregulation of <em>ldlr</em>, <em>ppar</em>α, and <em>abca1</em><span>, as well as decreased lipoprotein<span><span> lipase (LPL) and increased fatty acid synthase<span><span> (FAS) activity,suggesting an impact on fatty acid synthesis, cholesterol uptake, and lipid transport. Additionally, PFOS exposure led to impaired cholinergic neurotransmission, evidenced by a concentration-dependent inhibition of </span>acetylcholinesterase activity, altered gene expressions related to </span></span>neural development and function, and reduced Na</span></span>⁺/K⁺<span><span>-ATPase activity. STRING network analysis highlighted two distinct gene clusters related to lipid metabolism and cholinergic neurotransmission, with potential interactions through the pparα-creb1 pathway. Overall, this study provide important insights into the potential health risks associated with PFOS exposure, including dyslipidemia, cardiovascular disease, impaired glucose metabolism, and </span>neurotoxicity. Further research is needed to fully elucidate the underlying mechanisms and potential long-term effects of PFOS exposure.</span></p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"100 ","pages":"Article 107304"},"PeriodicalIF":2.9,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41147338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Juvenile variable stress modulates, in female but not in male Wistar rats, ethanol intake in adulthood","authors":"Agustín Salguero ,&nbsp;Agostina Barey ,&nbsp;Rodrigo García Virgolini ,&nbsp;Victoria Mujica ,&nbsp;María Carolina Fabio ,&nbsp;Roberto Sebastián Miranda-Morales ,&nbsp;Leonardo Marengo ,&nbsp;Rosana Camarini ,&nbsp;Ricardo Marcos Pautassi","doi":"10.1016/j.ntt.2023.107306","DOIUrl":"10.1016/j.ntt.2023.107306","url":null,"abstract":"<div><p><span>Early stress can increase vulnerability to psychopathological disorders, including substance use disorders. The effects of stress in the juvenile period of the rat, that extends between weaning and the onset of adolescence (equivalent to late human childhood), have received little attention. This study assessed short and long-term behavioral effects of juvenile stress, with a focus on effects on ethanol intake. Male and female Wistar rats were exposed to variable stress (restraint, elevated platform, forced swimming, and social instability) or to restraint stress only, between postnatal days 26 to 29 (PDs 26–29). During adolescence, patterns of anxiety (PD 31) and depression (PD 33), ethanol intake (PDs 36–45) and behavioral sensitivity to the effects of acute stress (PD 47) were evaluated. In adulthood, alcohol ingestion was assessed through two-bottle ethanol intake tests (PDs 75–85). An additional experiment measured blood ethanol levels after a limited access intake session in adolescence. Exposure to juvenile variable stress exerted very mild effects in adolescence, but reduced ethanol ingestion in adulthood, in females only. Ethanol intake during the limited access session was significantly correlated to blood alcohol levels. The results indicate that a schedule of juvenile variable stress that did not significantly alter anxiety-related </span>behaviors<span> induced, nonetheless, sexually dimorphic effects on ethanol intake in adulthood. Early stress exposure that reduced alcohol intake in Wistar rats has been associated with changes on brain opioid and dopamine receptors. These results highlight the impact of early stress exposure on adult female ethanol consumption and its possible underlying neurobiological changes, involving opioid and dopamine receptors.</span></p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"100 ","pages":"Article 107306"},"PeriodicalIF":2.9,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41179566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential gene expression profiling implicates altered network development in rat postnatal day 4 cortex following 4-Methylimidazole (4-MeI) induced maternal seizures","authors":"Abdull J. Massri ,&nbsp;Mackenzie Fitzpatrick ,&nbsp;Helen Cunny ,&nbsp;Jian-Liang Li ,&nbsp;G. Jean Harry","doi":"10.1016/j.ntt.2023.107301","DOIUrl":"10.1016/j.ntt.2023.107301","url":null,"abstract":"<div><p><span><span>Compromised maternal health leading to maternal seizures can have adverse effects<span> on the healthy development of offspring<span>. This may be the result of inflammation, hypoxia-ischemia, and altered GABA signaling. The current study examined cortical tissue from F2b (2nd litter of the 2nd generation) postnatal day 4 (PND4) offspring of female Harlan SD rats chronically exposed to the seizuregenic compound, 4-Methylimidazole (0, 750, or 2500 ppm 4-MeI). Maternal seizures were evident only at 2500 ppm 4-MeI. GABA related gene expression as examined by qRT-PCR and whole genome microarray showed no indication of disrupted GABA or glutamatergic signaling. Canonical pathway hierarchical clustering and multi-omics combinatory genomic (CNet) plots of differentially expressed genes (DEG) showed alterations in genes associated with regulatory processes of cell development including </span></span></span>neuronal differentiation and </span>synaptogenesis<span>. Functional enrichment analysis showed a similarity of cellular processes across the two exposure groups however, the genes comprising each cluster were primarily unique rather than shared and often showed different directionality. A dose-related induction of cytokine signaling was indicated however, pathways associated with individual cytokine signaling were not elevated, suggesting an alternative involvement of cytokine signaling. Pathways related to growth process and cell signaling showed a negative activation supporting an interpretation of disruption or delay in developmental processes at the 2500 ppm 4-MeI exposure level with maternal seizures. Thus, while GABA signaling was not altered as has been observed with maternal seizures, the pattern of DEG suggested a potential for alteration in neuronal network formation.</span></p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"100 ","pages":"Article 107301"},"PeriodicalIF":2.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An optimized radioimmunoassay for quantification of total serum thyroxine (T4) in fetal, neonatal, and pregnant rats","authors":"Katherine L. O'Shaughnessy,&nbsp;Michelle G. Hotchkiss,&nbsp;Angela K. Buckalew,&nbsp;Ashley S. Murr,&nbsp;Mary E. Gilbert,&nbsp;Tammy E. Stoker","doi":"10.1016/j.ntt.2023.107303","DOIUrl":"10.1016/j.ntt.2023.107303","url":null,"abstract":"<div><p><span><span>Identifying xenobiotics<span> that interrupt the thyroid axis has significant public health implications, given that thyroid hormones are required for brain development. As such, some developmental and </span></span>reproductive toxicology<span> (DART) studies now require or recommend serum total thyroxine<span><span> (T4) measurements in pregnant, lactating, and developing rats. However, serum T4 concentrations are normally low in the fetus and pup which makes quantification difficult. These challenges can be circumvented by technologies like </span>mass spectrometry<span>, but these approaches are expensive and not always widely available. To demonstrate the feasibility of measuring T4 using a commercially available assay, we examine technical replicates of rat serum samples measured both by liquid chromatography<span> mass spectrometry (LC/MS/MS) and radioimmunoassay (RIA). These samples were obtained from rats on gestational day 20 (dams and fetuses) or postnatal day 5 (pups), following maternal exposure to the </span></span></span></span></span>goitrogen<span> propylthiouracil (0–3 ppm) to incrementally decrease T4. We show that with assay modification, it is possible to measure serum T4 using low sample volumes (25–50 μL) by an RIA, including in the GD20 fetus exposed to propylthiouracil. This proof-of-concept study demonstrates the technical feasibility of measuring serum T4 in DART studies.</span></p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"100 ","pages":"Article 107303"},"PeriodicalIF":2.9,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the molecular mechanisms and developmental consequences of mercury (Hg) toxicity in zebrafish embryo-larvae: A comprehensive approach","authors":"Magda Carvalho Henriques ,&nbsp;Inês Carvalho ,&nbsp;Cátia Santos ,&nbsp;Maria Teresa Herdeiro ,&nbsp;Margarida Fardilha ,&nbsp;Maria Dimitriou Pavlaki ,&nbsp;Susana Loureiro","doi":"10.1016/j.ntt.2023.107302","DOIUrl":"10.1016/j.ntt.2023.107302","url":null,"abstract":"<div><p>Mercury (Hg) is a global contaminant affecting aquatic ecosystems' health. Chronic exposure to Hg has shown that the normal development of zebrafish embryo-larvae is affected. However, the molecular mechanisms behind the toxicity of Hg on fish embryonic development are still poorly understood. This work aimed to investigate the effects of Hg exposure on zebrafish embryo-larvae using a combined approach at individual (mortality, embryo development and locomotor behavior) and biochemical (neurotoxicity and oxidative stress enzymatic activities and protein phosphatase expression) levels. The Fish Embryo Toxicity assay followed the Organization for Economic Cooperation and Development Guideline 236 and used a concentration range between 13 and 401 μg Hg/L. Lethal and developmental endpoints were examined at 24, 48, 72 and 96 hpf. Biochemical markers, including Acetylcholinesterase (AChE), Catalase (CAT), Glutathione Reductase (GR), and Glutathione-<em>S</em>-Transferase (GST) activities and, for the first time, the expression of the protein phosphatase 1 gamma (PP1γ) was assessed after 24, 48, 72 and 96 h of exposure to 10 and 100 μg Hg/L. The behavioral effects of a sublethal range of Hg (from 0.8 to 13 μg Hg/L) were assessed using an automated video tracking system at 120 hpf. Several developmental abnormalities on zebrafish embryos and larvae, including pericardial edema, spin and tail deformities and reduced rate of consumption of the yolk sac, were found after exposure to Hg (LC₅₀ at 96 hpf of 139 μg Hg/L) with EC₅₀ values for total malformations ranging from 22 to 264 μg Hg/L. After 96 hpf, no significant effects were observed in the CAT and GR activities. However, an increase in the GST activity in a concentration and time-dependent manner was found, denoting possible stress-related adaptation of zebrafish embryos to deleterious effects of Hg exposure. The AchE activity showed a response pattern in line with the behavioral responses. At the lowest concentration tested, no significant effects were found for the AChE activity, whereas a decrease in AChE activity was observed at 100 μg Hg/L, suggesting that exposure to Hg induced neurotoxic effects in zebrafish embryos which in turn may explain the lack of equilibrium found in this study (EC₅₀ at 96 hpf of 83 μg Hg/L). Moreover, a decrease in the PP1γ expression was found after 96 h of exposure to 10 and 100 μg Hg/L. Thus, we suggest that Hg may be an inhibitor of PP1γ in zebrafish embryos-larvae and thus, along with the alterations in the enzymatic activity of GST, explain some of the developmental malformations observed, as well as the lack of equilibrium. Hence, in this study, we propose the use of PP1 expression, in combination with apical and biochemical endpoints, as a precursor for assessing Hg's toxic mechanism on embryonic development.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"100 ","pages":"Article 107302"},"PeriodicalIF":2.9,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41133063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}