Neurotoxicology and teratology最新文献

{"title":"The U.S. PFAS exposure burden calculator for 2017–2018: Application to the HOME Study, with comparison of epidemiological findings from NHANES","authors":"Shelley H. Liu ,&nbsp;Yitong Chen ,&nbsp;Leah Feuerstahler ,&nbsp;Aimin Chen ,&nbsp;Anne Starling ,&nbsp;Dana Dabelea ,&nbsp;Xiaobin Wang ,&nbsp;Kim Cecil ,&nbsp;Bruce Lanphear ,&nbsp;Kimberly Yolton ,&nbsp;Joseph M. Braun ,&nbsp;Jessie P. Buckley","doi":"10.1016/j.ntt.2024.107321","DOIUrl":"10.1016/j.ntt.2024.107321","url":null,"abstract":"<div><h3>Background</h3><p><span>The 2017–2018 U.S. PFAS exposure burden calculator was designed to provide a summary exposure score for </span><em>per</em>- and polyfluoroalkyl substances (PFAS) mixtures using targeted PFAS analyte data. Its aim was to place PFAS burden score estimates onto a common scale based on nationally representative U.S. reference ranges from 2017 to 2018, enabling comparisons of overall PFAS burden scores across studies even if they did not measure the same set of PFAS analytes.</p></div><div><h3>Objective</h3><p>To use the U.S. PFAS exposure burden calculator for comparing the same mixture of PFAS compounds in similarly aged adolescents and their associations with cardiometabolic outcomes in the HOME Study and NHANES between 2015 and 2018.</p></div><div><h3>Methods</h3><p>We applied the PFAS burden calculator to 8 PFAS analytes measured in the serum of adolescents from the HOME Study (Cincinnati, Ohio; age range 11–14 years; years: 2016–2019; <em>n</em> = 207) and NHANES (US; age range 12–14 years; years 2015–2018; <em>n</em> = 245). We used the non-parametric Mann-Whitney <em>U</em> test and chi-squared test to compare the two study samples. In both studies, we examined associations of PFAS burden scores with the same cardiometabolic outcomes, adjusted for the same core set of covariates using regression analyses. We conducted sensitivity analyses to verify robustness of exposure-outcome associations, by accounting for measurement error of PFAS burden scores.</p></div><div><h3>Results</h3><p>PFAS burden scores were significantly different (<em>p</em> = 0.004) between the HOME Study (median: 0.00, interquartile range − 0.37, 0.34) and the NHANES samples (median: 0.04, IQR -0.11, 0.54), while no significant difference was found for PFAS summed concentrations (<em>p</em><span> = 0.661). In the HOME Study, an interquartile (IQR) increase in PFAS burden score was associated with higher total cholesterol [7.0 mg/dL, 95% CI: 0.6, 13.4]; HDL [2.8 mg/dL, 95% CI: 0.4, 5.2]; LDL [5.9 mg/dL, 95% CI: 0.5, 11.3], insulin [0.1 log(mIU/L), 95% CI: 0.01, 0.2], and HOMA-IR [0.1, 95% CI: 0.01, 0.2]. In NHANES, an IQR increase in PFAS burden score was associated with higher diastolic blood pressure [2.4 mmHg, 95% CI: 0.4, 4.4] but not with other outcomes. Sensitivity analyses in the HOME Study and NHANES were consistent with the main findings.</span></p></div><div><h3>Conclusions</h3><p>Performance of the U.S. PFAS exposure burden calculator was similar in a local versus national sample of adolescents, and may be a useful tool for the assessment of PFAS mixtures across studies.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107321"},"PeriodicalIF":2.9,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139464713","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":"Abuse-like toluene exposure during early adolescence alters subsequent ethanol and cocaine behavioral effects and brain monoamines in male mice","authors":"Cameron J. Davidson ,&nbsp;John H. Hannigan ,&nbsp;Shane A. Perrine ,&nbsp;Scott E. Bowen","doi":"10.1016/j.ntt.2023.107317","DOIUrl":"10.1016/j.ntt.2023.107317","url":null,"abstract":"<div><p>Currently, there is a gap in understanding the neurobiological impact early adolescent toluene exposure has on subsequent actions of other drugs. Adolescent (PND 28–32) male Swiss-Webster mice (<em>N</em> = 210) were exposed to 0, 2000, or 4000 ppm of toluene vapor for 30 min/day for 5 days. Immediately following the last toluene exposure (PND 32; <em>n</em><span> = 15) or after a short delay (PND 35; n = 15), a subset of subjects' brains was collected for monoamine<span> analysis. Remaining mice were assigned to one of two abstinence periods: a short 4-day (PND 36) or long 12-day (PND 44) delay after toluene exposure. Mice were then subjected to a cumulative dose response assessment of either cocaine (0, 2.5, 5, 10, 20 mg/kg; </span></span><em>n</em><span><span><span> = 60), ethanol (0, 0.5, 1, 2, 4 g/kg; n = 60), or saline (5 control injections; n = 60). Toluene concentration-dependently increased locomotor activity during exposure. When later challenged, mice exposed previously to toluene were significantly less active after cocaine (10 and 20 mg/kg) compared to air-exposed controls. Animals were also less active at the highest dose of alcohol (4 g/kg) following prior exposure to 4000 ppm when compared to air-exposed controls. Analysis of monoamines and their metabolites using High Pressure </span>Liquid Chromatography<span> (HPLC) within the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), </span></span>dorsal striatum<span> (dSTR), and ventral tegmental area (VTA) revealed subtle effects on monoamine or metabolite levels following cumulative dosing that varied by drug (cocaine and ethanol) and abstinence duration. Our results suggest that early adolescent toluene exposure produces behavioral desensitization to subsequent cocaine-induced locomotor activity with subtle enhancement of ethanol's depressive effects and less clear impacts on levels of monoamines.</span></span></p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"101 ","pages":"Article 107317"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139396688","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":"The relationship of prenatal acetaminophen exposure and attention-related behavior in early childhood","authors":"Megan L. Woodbury ,&nbsp;Sarah D. Geiger ,&nbsp;Susan L. Schantz","doi":"10.1016/j.ntt.2024.107319","DOIUrl":"10.1016/j.ntt.2024.107319","url":null,"abstract":"<div><p>Acetaminophen is currently the only analgesic considered safe for use throughout pregnancy, but recent studies indicate that prenatal exposure to acetaminophen may be related to poorer neurodevelopmental outcomes. Multiple studies have suggested that it may be associated with attention problems, but few have examined this association by trimester of exposure. The Illinois Kids Development Study is a prospective birth cohort located in east-central Illinois. Exposure data were collected between December 2013 and March 2020, and 535 newborns were enrolled during that period. Mothers reported the number of times they took acetaminophen at six time points across pregnancy. When children were 2, 3, and 4 years of age, caregivers completed the Child Behavior Checklist for ages 1.5–5 years (CBCL). Associations of acetaminophen use during pregnancy with scores on the Attention Problems and ADHD Problems syndrome scales, the Internalizing and Externalizing Behavior composite scales, and the Total Problems score were evaluated. Higher acetaminophen exposure during the second trimester of fetal development was associated with higher Attention Problems, ADHD Problems, Externalizing Behavior, and Total Problems scores at ages 2 and 3. Higher second trimester exposure was only associated with higher Externalizing Behavior and Total Problems scores at 4 years. Higher cumulative exposure across pregnancy was associated with higher Attention Problems and ADHD Problems scores at ages 2 and 3. Findings suggest that prenatal acetaminophen exposure, especially during the second trimester, may be related to problems with attention in early childhood.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"101 ","pages":"Article 107319"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0892036224000011/pdfft?md5=eb9f57c6c94f8b01bf22fac54faca271&pid=1-s2.0-S0892036224000011-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139396834","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":"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}