Gale A. Richardson , Natacha M. De Genna , Jennifer A. Willford , Lidush Goldschmidt
{"title":"Pathways from prenatal cocaine exposure to adult substance use and behavior","authors":"Gale A. Richardson , Natacha M. De Genna , Jennifer A. Willford , Lidush Goldschmidt","doi":"10.1016/j.ntt.2024.107335","DOIUrl":"10.1016/j.ntt.2024.107335","url":null,"abstract":"<div><p>This is a report from the most recent adult follow-up of the longest running cohort study of prenatal cocaine exposure (PCE), in which women were enrolled prenatally and offspring were assessed in infancy, childhood, adolescence, and young adulthood. In previous studies, PCE was linked to offspring behavior problems such as early substance use and externalizing behavior problems. The current analyses examine pathways from PCE to behavioral outcomes in offspring at the 25-year assessment. Prenatal cocaine exposure was moderate in this cohort; most women decreased or discontinued use after the first trimester. During the first and third trimesters, 38% and 11% used cocaine, respectively. This represents the most common pattern of PCE in non-treatment samples. At this phase, the adult offspring were, on average, 27.3 years old (range = 25–30), had 13.4 years of education, 83% were employed, 55% were Black, and 55% were female. Offspring who were exposed to cocaine during the first trimester were significantly more likely to use marijuana in the past year, report more arrests, and have poorer scores on a decision-making task, controlling for other prenatal substance exposure, demographic, and socioeconomic factors. In mediation analyses, there were indirect pathways from PCE to current marijuana use through early initiation of marijuana use and 21-year marijuana use, and through 15-year status offenses and 21-year marijuana use. There was also an indirect pathway from PCE to lifetime arrests through early initiation of marijuana use and 21-year Conduct Disorder, although the direct pathway from PCE to arrests also remained significant. These findings are consistent with those from previous phases and are an indication that there are detrimental associations with PCE that persist across developmental stages and into adulthood.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107335"},"PeriodicalIF":2.9,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906211","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}
Beth A. Bailey, Haley Kopkau, Katherine Nadolski, Phoebe Dodge
{"title":"Impact of in utero tobacco exposure on fetal growth: Amount of exposure and second trimester fetal growth measurements","authors":"Beth A. Bailey, Haley Kopkau, Katherine Nadolski, Phoebe Dodge","doi":"10.1016/j.ntt.2024.107334","DOIUrl":"https://doi.org/10.1016/j.ntt.2024.107334","url":null,"abstract":"<div><h3>Background</h3><p>Research reveals small and inconsistent findings linking prenatal tobacco exposure and early fetal growth, but failure to consider confounding and amount of exposure many explain inconsistencies.</p></div><div><h3>Goal</h3><p>To examine whether fetal growth effects following exposure to tobacco are evident in the second trimester, specific to certain growth parameters, and dose dependent.</p></div><div><h3>Methods</h3><p>Participants were pregnant women (64 smokers, 100 controls) with no other drug use. Available data included background/medical information and ultrasound measurements coded as percentiles.</p></div><div><h3>Results</h3><p>Controlling for background differences, 10+ cig/day predicted a 10+ percentile point reduction in estimated fetal weight, femur length, head circumference, and biparietal diameter compared to non-exposed controls. Exposure to <10 cig/day predicted significant reduction in only biparietal diameter. Exposure was unrelated to abdominal circumference.</p></div><div><h3>Conclusions</h3><p>Results demonstrate utility of considering amount of exposure when examining/quantifying fetal growth effects, and suggest even reduction in early pregnancy smoking may positively benefit aspects of fetal development.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107334"},"PeriodicalIF":2.9,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139738090","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}
Stephane A. Beaudin , Samantha Gorman , Naomi Schilpp , David Woodfin , Barbara J. Strupp , Donald R. Smith
{"title":"Sensorimotor dysfunction due to developmental manganese exposure is less severe in adult female than male rats and partially improved by acute methylphenidate treatment","authors":"Stephane A. Beaudin , Samantha Gorman , Naomi Schilpp , David Woodfin , Barbara J. Strupp , Donald R. Smith","doi":"10.1016/j.ntt.2024.107330","DOIUrl":"10.1016/j.ntt.2024.107330","url":null,"abstract":"<div><p>Epidemiological studies have reported associations between elevated manganese (Mn) exposure and poorer psychomotor performance in children. Our studies in adult male rats have established that this relationship is causal and that prolonged methylphenidate (MPH) treatment is efficacious in treating this area of dysfunction. However, it is unclear if sensitivity to these Mn deficits differs between females and males, and whether existing pharmacological therapies are efficacious in improving sensorimotor dysfunction in females. To address these questions, we used our rat model of childhood environmental Mn exposure and the Montoya staircase test to determine whether 1) there are sex differences in the lasting sensorimotor dysfunction caused by developmental Mn exposure, and 2) MPH treatment is efficacious in ameliorating the sensorimotor deficits in females. Female and male neonates were treated orally with Mn (50 mg Mn/kg/d) from postnatal day 1 to 21 and evaluated for skilled forelimb sensorimotor performance as adults. Subsequently, the efficacy of acute oral MPH treatment (doses of 0, 0.5, and 3.0 mg MPH/kg/d) was assessed in females using a within-subject MPH treatment design. Developmental postnatal Mn exposure produced lasting sensorimotor reaching and grasping deficits that were milder in females than in males. Acute MPH treatment of Mn-exposed females with the 0.5 mg/kg/d dose attenuated the reaching dysfunction without alleviating grasping dysfunction. These findings show sex-based variations in sensitivity to the sensorimotor impairment caused by developmental Mn exposure, and they are consistent with prior studies showing less vulnerability of females to Mn-induced dysfunction in other functional domains, possibly due to the protective effects of estrogen. Given our previous work showing the efficacy of MPH treatment to alleviate Mn-induced inattention, impulsiveness, and sensorimotor dysfunctions in adult male rats, they also highlight the need for further research into sex-based differences in cognitive and behavioral areas of brain function, and the efficacy of therapeutics in treating behavioral dysfunction in females.</p><p>Supported by NIEHS R01ES028369.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107330"},"PeriodicalIF":2.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672254","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}
Judith L.A. Fishburn , Heather L. Larson , An Nguyen , Chloe J. Welch , Taylor Moore , Aliyah Penn , Johnathan Newman , Anthony Mangino , Erin Widman , Rana Ghobashy , Jocelyn Witherspoon , Wendy Lee , Kimberly A. Mulligan
{"title":"Bisphenol F affects neurodevelopmental gene expression, mushroom body development, and behavior in Drosophila melanogaster","authors":"Judith L.A. Fishburn , Heather L. Larson , An Nguyen , Chloe J. Welch , Taylor Moore , Aliyah Penn , Johnathan Newman , Anthony Mangino , Erin Widman , Rana Ghobashy , Jocelyn Witherspoon , Wendy Lee , Kimberly A. Mulligan","doi":"10.1016/j.ntt.2024.107331","DOIUrl":"10.1016/j.ntt.2024.107331","url":null,"abstract":"<div><p>Bisphenol F (BPF) is a potential neurotoxicant used as a replacement for bisphenol A (BPA) in polycarbonate plastics and epoxy resins. We investigated the neurodevelopmental impacts of BPF exposure using <em>Drosophila melanogaster</em> as a model. Our transcriptomic analysis indicated that developmental exposure to BPF caused the downregulation of neurodevelopmentally relevant genes, including those associated with synapse formation and neuronal projection. To investigate the functional outcome of BPF exposure, we evaluated neurodevelopmental impacts across two genetic strains of <em>Drosophila— w1118</em> (control) and the Fragile X Syndrome (FXS) model—by examining both behavioral and neuronal phenotypes. We found that BPF exposure in <em>w1118 Drosophila</em> caused hypoactive larval locomotor activity, decreased time spent grooming by adults, reduced courtship activity, and increased the severity but not frequency of β-lobe midline crossing defects by axons in the mushroom body. In contrast, although BPF reduced peristaltic contractions in FXS larvae, it had no impact on other larval locomotor phenotypes, grooming activity, or courtship activity. Strikingly, BPF exposure reduced both the severity and frequency of β-lobe midline crossing defects in the mushroom body of FXS flies, a phenotype previously observed in FXS flies exposed to BPA. This data indicates that BPF can affect neurodevelopment and its impacts vary depending on genetic background. Further, BPF may elicit a gene-environment interaction with <em>Drosophila fragile X messenger ribonucleoprotein 1</em> (<em>dFmr1</em>)—the ortholog of human <em>FMR1</em>, which causes fragile X syndrome and is the most common monogenetic cause of intellectual disability and autism spectrum disorder.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107331"},"PeriodicalIF":2.9,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0892036224000138/pdfft?md5=642cee3baa0fbaa8575ca68d5cf513d4&pid=1-s2.0-S0892036224000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139659353","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}
Jian Lin , Yanqi Lou , Zhenkai Sun , Dongliang Pan , Lei Lei , Yang Song , Changjiang Huang , Jiangfei Chen
{"title":"DDT and titanium dioxide nanoparticle coexposure induced neurobehavioral deficits in zebrafish","authors":"Jian Lin , Yanqi Lou , Zhenkai Sun , Dongliang Pan , Lei Lei , Yang Song , Changjiang Huang , Jiangfei Chen","doi":"10.1016/j.ntt.2024.107323","DOIUrl":"10.1016/j.ntt.2024.107323","url":null,"abstract":"<div><p><span>Both dichlorodiphenyltrichloroethane<span> (DDT) and titanium dioxide nanoparticle (TiO</span></span><sub>2</sub> NP) have worldwide-scale commercial applications, resulting in their co-pollution in the ecosystems and posing combined health risks. However, there is a lack of toxicity studies for the interactions of DDT and TiO<sub>2</sub><span> NP in the environmental relevant concentrations. In this study, we characterized the coexposures using a zebrafish waterborne exposure approach and evaluated the neurotoxicity response of the treated embryos or adults. Our results showed that DDT/TiO</span><sub>2</sub> NP coexposure enhanced the DDT accumulation in vivo and increased the larval locomotor. The chronic DDT/TiO<sub>2</sub> NP coexposure did not affect the overall survival rate, sex ratio and growth. However, DDT/TiO<sub>2</sub><span><span> NP coexposure severely affected the adult locomotor activity, social contact, shoaling and aggressive behaviors<span> compared to single treatment groups or controls. These adult behavioral deficits were accompanied by changes in neurotransmitter<span> acetylcholine (ACH) level in the brain and muscle tissues, as well as </span></span></span>neural development genes expression activation of growth-associated protein 43 (</span><em>gap43</em><span>) and synaptic vesicle<span> glycoprotein 2 (</span></span><em>sv2</em>) in the brain. The significantly increased ACH level and the activated neural genes expression in the DDT/TiO<sub>2</sub> NP co-exposed fish may account for the observed hyperactivity and social deficits.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107323"},"PeriodicalIF":2.9,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557480","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}
Amanda C. Wylie , Sarah J. Short , Rebecca C. Fry , W. Roger Mills-Koonce , Cathi B. Propper
{"title":"Maternal prenatal lead levels and neonatal brain volumes: Testing moderations by maternal depressive symptoms and family income","authors":"Amanda C. Wylie , Sarah J. Short , Rebecca C. Fry , W. Roger Mills-Koonce , Cathi B. Propper","doi":"10.1016/j.ntt.2024.107322","DOIUrl":"10.1016/j.ntt.2024.107322","url":null,"abstract":"<div><p><span><span><span><span>There is considerable evidence that prenatal lead exposure is detrimental to child cognitive and socio-emotional development. Further evidence suggests that the effects of prenatal lead on developmental outcomes may be conditional upon exposure to social stressors, such as maternal depression and low socioeconomic status. However, no studies have examined associations between these co-occurring stressors during pregnancy and neonatal brain volumes. Leveraging a sample of 101 mother-infant dyads followed beginning in mid-pregnancy, we examined the main effects of prenatal urinary lead levels on neonatal lateralized brain volumes (left and right </span>hippocampus, </span>amygdala, </span>cerebellum, frontal lobes) and total gray matter. We additionally tested for moderations between lead and depressive symptoms and between lead and family income relative to the federal poverty level (FPL) on the same neurodevelopmental outcomes. Analyses of main effects indicated that prenatal lead was significantly (</span><em>ps</em> < 0.05) associated with reduced right and left amygdala volumes (<em>βs</em> = −0.23- -0.20). The testing and probing of cross-product interaction terms using simple slopes indicated that the negative effect of lead on the left amygdala was conditional upon mothers having low depressive symptoms or high income relative to the FPL. We interpret the results in the context of trajectories of prenatal and postnatal brain development and susceptibility to low levels of prenatal lead in the context of other social stressors.</p></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"102 ","pages":"Article 107322"},"PeriodicalIF":2.9,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139497652","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}
Shelley H. Liu , Yitong Chen , Leah Feuerstahler , Aimin Chen , Anne Starling , Dana Dabelea , Xiaobin Wang , Kim Cecil , Bruce Lanphear , Kimberly Yolton , Joseph M. Braun , Jessie P. Buckley
{"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 , Yitong Chen , Leah Feuerstahler , Aimin Chen , Anne Starling , Dana Dabelea , Xiaobin Wang , Kim Cecil , Bruce Lanphear , Kimberly Yolton , Joseph M. Braun , 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}
Cameron J. Davidson , John H. Hannigan , Shane A. Perrine , Scott E. Bowen
{"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 , John H. Hannigan , Shane A. Perrine , 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}
Megan L. Woodbury , Sarah D. Geiger , Susan L. Schantz
{"title":"The relationship of prenatal acetaminophen exposure and attention-related behavior in early childhood","authors":"Megan L. Woodbury , Sarah D. Geiger , 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}
Angel Biju , Emma Ivantsova , Christopher L. Souders II , Cole English , Lev Avidan , Christopher J. Martyniuk
{"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 , Emma Ivantsova , Christopher L. Souders II , Cole English , Lev Avidan , 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}