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Neurotoxicology and Teratology

Lidush Goldschmidt, Gale A Richardson, Natacha M De Genna, Marie D Cornelius, Nancy L Day
Studies have shown that prenatal alcohol exposure (PAE) is related to drinking problems during adulthood, but the level of prenatal exposure associated with young adults' quantity and frequency of alcohol use and drinking problems has not yet been established. The relation between PAE and offspring levels of alcohol use and alcohol abuse/dependency was examined in 608 22-year-olds. Mothers were recruited in early pregnancy and maternal alcohol use data were collected for each trimester of pregnancy. The offspring were assessed at multiple phases from birth to young adulthood...
November 3, 2018: Neurotoxicology and Teratology
Aline Haab Lutte, Luiza Reali Nazario, Júlia Huppes Majolo, Talita Carneiro Brandão Pereira, Stefani Altenhofen, Adilio da Silva Dadda, Maurício Reis Bogo, Rosane Souza Da Silva
Prenatal alcohol exposure causes alterations to the brain and can lead to numerous cognitive and behavioral outcomes. Long-lasting effects of early ethanol exposure have been registered in glutamatergic and dopaminergic systems. The purinergic system has been registered as an additional target of ethanol exposure. The objective of this research was to evaluate if the ecto‑5'‑nucleotidase and adenosine deaminase activities and gene expression of adult zebrafish exposed to 1% ethanol during early development could be part of the long-lasting targets of ethanol...
October 24, 2018: Neurotoxicology and Teratology
Keith Morris-Schaffer, Marissa Sobolewski, Kevin Welle, Katherine Conrad, Min Yee, Michael A O'Reilly, Deborah A Cory-Slechta
Epidemiological evidence indicates an association between early-life exposure to air pollution and preterm birth. Thus, it is essential to address the subsequent vulnerability of preterm infants, who are exposed to unique factors at birth including hyperoxia, and subsequently to air pollution. Health effects of air pollution relate to particle size and the ultrafine particulate component (<100 nm) is considered the most reactive. We previously reported neonatal mice exposed to hyperoxia (60% oxygen), mimicking preterm oxygen supplementation, for the first 4 days of life, followed by exposure to concentrated ambient ultrafine particles (CAPS) from postnatal day (PND) 4-7 and 10-13 exhibited deficits in acquisition of performance on a fixed interval (FI) schedule of reinforcement, a behavioral paradigm rewarding the first response at the end of a fixed interval of time...
October 11, 2018: Neurotoxicology and Teratology
Ainhoa Alzualde, Mamta Behl, Nisha S Sipes, Jui-Hua Hsieh, Aintzane Alday, Raymond R Tice, Richard S Paules, Arantza Muriana, Celia Quevedo
Following the voluntary phase-out of brominated flame retardants (BFRs) due to their environmental persistence and toxicity, the organophosphorus flame retardants (OPFRs) are emerging replacements. However, there is limited information on the potential human health effects of the OPFRs. Zebrafish embryos are a viable vertebrate model organism with many advantages for high throughput testing toward human hazard assessment. We utilized zebrafish embryos to assess developmental toxicity, neurotoxicity, cardiotoxicity and hepatotoxicity, of eight replacement OPFRs: (triphenyl phosphate [TPHP], isopropylated phenyl phosphate [IPP], 2-ethylhexyl diphenyl phosphate [EHDP], tert-butylated phenyl diphenyl phosphate [BPDP], trimethyl phenyl phosphate [TMPP], isodecyl diphenyl phosphate [IDDP], tris(1,3-dichloroisopropyl) phosphate [TDCIPP], and tris(2-chloroethyl) phosphate [TCEP]) and two BFRs (3,3',5,5'- tetrabromobisphenol A [TBBPA] and 2,2'4,4'-brominated diphenyl ether [BDE-47])...
October 9, 2018: Neurotoxicology and Teratology
Fangjie Cao, Christopher L Souders, Pengfei Li, Sen Pang, Lihong Qiu, Christopher J Martyniuk
The objectives of this study were to compare the biological responses in developing zebrafish to two organophosphate insecticides, chlorpyrifos (CPF) and diazinon (DZN). Zebrafish embryos were exposed to either solvent control (0.1% DMSO, v/v), or one dose of 0.1, 1.0, 10.0 and 25.0 μM CPF, as well as one dose of 0.1, 1.0, 10.0 and 100.0 μM DZN for 96 h. CPF at 10.0 and 25.0 μM caused 70-80% and 100% mortality in embryos after 96 h exposure, whereas embryos treated with 10.0 and 100.0 μM DZN showed 30-40% and 70-80% lethality...
October 2, 2018: Neurotoxicology and Teratology
Laura R Stroud, George D Papandonatos, Meaghan McCallum, Tessa Kehoe, Amy L Salisbury, Marilyn A Huestis
Tobacco and marijuana are some of the most common prenatal substance exposures worldwide. The social acceptability and political landscape of marijuana and its potency have changed dramatically in the last two decades leading to increased use by pregnant women. Despite evidence for increasing marijuana use and high rates of co-use of tobacco (TOB) and marijuana (MJ) during pregnancy, the impact of prenatal exposure to each substance is typically studied in isolation. We investigated the influence of co-exposure to TOB and MJ on infant neurobehavioral development over the first postnatal month...
September 26, 2018: Neurotoxicology and Teratology
Natacha M De Genna, Lidush Goldschmidt, Gale A Richardson, Marie D Cornelius, Nancy L Day
Co-use of cannabis and tobacco is increasingly common among women and is associated with tobacco and cannabis dependence and poorer cessation outcomes. However, no study has examined maternal patterns of co-use over time, or the impact of maternal co-use on co-use and drug problems in adult offspring. Pregnant women (M age = 23, range = 18-42; 52% African American, 48% White) were asked about substance use during each trimester of pregnancy, and at 8 and 18 months, 3, 6, 10, 14, 16, and 22 years postpartum...
September 15, 2018: Neurotoxicology and Teratology
Madeleine Cleal, Matthew O Parker
The damaging effects of alcohol on a developing fetus are well known and cause a range of conditions known as fetal alcohol spectrum disorder (FASD). High levels of alcohol exposure lead to physical deformity and severe cognitive deficits, but more moderate exposure leads to a range of subtle cognitive effects such as reduced social behavior, higher propensity to develop addictions, and reduced spatial working memory. Previous studies have demonstrated that following exposure to relatively low levels of ethanol during early brain development (equivalent in humans to moderate exposure) zebrafish display a range of social and behavioral differences...
September 7, 2018: Neurotoxicology and Teratology
Takashi Yorifuji, Shigeru Takaoka, Philippe Grandjean
Severe methylmercury poisoning occurred in Minamata and neighboring communities in Japan during the 1950s and 1960s. A considerable number of children were born with conditions resembling cerebral palsy, later known as congenital Minamata disease. Although surviving patients are now in their 50s or 60s, few assessments of functional capacities in daily living have been performed. We assessed the changes in Activities of Daily Living (ADL) status of 11 patients over a 10-year period. For assessment of ADL, we applied the Barthel Index (BI) and the Functional Independence Measure (FIM)...
September 2018: Neurotoxicology and Teratology
Stephanie A Godleski, Shannon Shisler, Rina D Eiden, Marilyn A Huestis
Use and co-use of tobacco and marijuana during pregnancy are associated with the development of social, cognitive, and behavioral problems for infants and children. However, less is known about the potential developmental impact of the use of tobacco and marijuana in tandem. The present study examined an etiological model for the development of externalizing behavior problems (EBP) in early childhood in a high risk sample (N = 247) of mother-infant dyads with prospective data from pregnancy to 36 months of child age...
September 2018: Neurotoxicology and Teratology
Jun-Sheng Tian, Shao-Bo Liu, Xiao-Yan He, Huan Xiang, Jian-Li Chen, Yao Gao, Yu-Zhi Zhou, Xue-Mei Qin
There are three types of differentiated (un-, poorly- and well-differentiated) PC12 cells, which have been widely used as a model system for depression studies after the administration of corticosterone (CORT). In order to investigate the underlying metabolic profiles of CORT-induced PC12 cells and evaluate the suitable differentiated types of PC12 cells for use in depressive studies, proton nuclear magnetic resonance (1 H NMR) metabolomics coupled with network analysis approaches were employed. The results showed that CORT induced metabolic alterations in PC12 cells...
September 2018: Neurotoxicology and Teratology
Zhenming Kang, Wenji Xie, Wenqin Xie, Shunyuan Li, Rushuang Chen
Dexmedetomidine is a local anesthetic adjuvant that exerts neuroprotective effects in addition to its sedative and analgesic properties. However, it is not clear whether dexmedetomidine causes any neurotoxicity in neonates. We injected dexmedetomidine alone or in combination with ropivacaine to induce brachial plexus block in rats of different age, corresponding to human neonate, childhood, adolescence and adulthood. We then examined pro-inflammatory cytokines and activated caspase 3 to determine the neurotoxicity effects...
September 2018: Neurotoxicology and Teratology
Jennifer A Willford, Dil Singhabahu, Athula Herat, Gale A Richardson
Prenatal drug exposure, including cocaine, alcohol, marijuana, and tobacco, is associated with deficits in behavioral regulation and attention. Using fMRI, the objective of this study was to characterize the association between prenatal cocaine exposure (PCE) and the underlying neural substrates associated with behavioral outcomes of attention. Forty-seven young adults were recruited for this study from the ongoing Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of the effects of PCE on growth, behavior, and cognitive function...
September 2018: Neurotoxicology and Teratology
Afzaal N Mohammed, Navatha Alugubelly, Barbara L Kaplan, Russell L Carr
The gestational and adolescent periods are critically important for brain development and exposure to Δ9‑tetrahydrocannabinol (Δ9-THC) during these periods results in long term behavioral and biochemical abnormalities in laboratory animals. However, recent reports indicate a dramatic rise in oral Δ9-THC exposure in young children but the effects of this exposure scenario have not been adequately investigated. Using a model designed to mimic childhood exposure, male and female rat pups were orally exposed to either corn oil or 10 mg/kg Δ9-THC daily from postnatal days 10-16...
September 2018: Neurotoxicology and Teratology
Bonnie L Robinson, Melanie Dumas, Syed F Ali, Merle G Paule, Qiang Gu, Jyotshna Kanungo
Ketamine, a phencyclidine derivative, is an antagonist of the Ca2+ -permeable N-methyl-d-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic and has been implicated in developmental neurotoxicity. Ketamine has also been shown to deplete ATP in mammalian cells. Our previous studies showed that acetyl l-carnitine (ALCAR) prevented ketamine-induced cardiotoxicity and neurotoxicity in zebrafish embryos. Based on our finding that ALCAR's protective effect was blunted by oligomycin A, an inhibitor of ATP synthase, we further investigated the effects of ketamine and ALCAR on ATP levels, mitochondria and ATP synthase in zebrafish embryos...
September 2018: Neurotoxicology and Teratology
Holly Richendrfer, Robbert Creton
Antidepressants are used by a substantial number of women in their childbearing years. Treatment may continue during pregnancy, since untreated depression poses a risk to the mother and child. However, many antidepressants readily pass through the placental barrier to reach the fetus or may be ingested by the newborn via breastmilk. Little is known about the effects of antidepressants on brain development and subsequent behavior in young children. In the current study, we used zebrafish as a model system to examine the neurodevelopmental effects of three commonly prescribed antidepressants, sertraline, duloxetine and bupropion...
September 2018: Neurotoxicology and Teratology
Samantha Mahabir, Diptendu Chatterjee, Robert Gerlai
The zebrafish has been successfully employed to model and study the effects of embryonic alcohol exposure. Short exposure to low alcohol concentrations during embryonic development has been shown to significantly disrupt social behavior as well as the dopaminergic and serotoninergic systems in zebrafish. However, analysis of potential effects of embryonic alcohol exposure on other amino acid neurotransmitter systems has not been performed. Here we analyzed neurochemicals obtained from adult AB and TU strain zebrafish that were immersed in 0...
July 2018: Neurotoxicology and Teratology
Suena H Massey, Daniel K Mroczek, David Reiss, Emily S Miller, Jessica A Jakubowski, Eileen K Graham, Shannon M Shisler, Meaghan McCallum, Marilyn A Huestis, Jody M Ganiban, Daniel S Shaw, Leslie D Leve, Rina D Eiden, Laura R Stroud, Jenae M Neiderhiser
BACKGROUND: Methodologic challenges related to the concomitant use (co-use) of substances and changes in policy and potency of marijuana contribute to ongoing uncertainty about risks to fetal neurodevelopment associated with prenatal marijuana use. In this study, we examined two biomarkers of fetal neurodevelopmental risk-birth weight and length of gestation-associated with prenatal marijuana use, independent of tobacco (TOB), alcohol (ALC), other drug use (OTH), and socioeconomic risk (SES), in a pooled sample (N = 1191) derived from 3 recent developmental cohorts (2003-2015) with state-of-the-art substance use measures...
July 2018: Neurotoxicology and Teratology
Victoria H Coleman-Cowger, Emmanuel A Oga, Erica N Peters, Katrina Mark
Use of Cannabis and use of tobacco overlap, and co-use of Cannabis and tobacco has increased over the past decade among adults. The current study aims to document the prevalence and correlates of co-use of Cannabis and tobacco cigarettes among adult pregnant women utilizing secondary data from a larger study that compared and validated screeners for illicit and prescription drug use during pregnancy. Pregnant women (N = 500; 71% African American; 65% never married, average age of 28 years) were recruited from two urban University obstetric clinics between January and December 2017...
July 2018: Neurotoxicology and Teratology
Kara Montgomery, Caleb Corona, Rebekah Frye, Reid Barnett, Andrew Bailey, Vanessa A Fitsanakis
Mancozeb (MZ), an organic-metal fungicide used predominantly on vegetables and fruits, has been linked to neurodegeneration and behavioral disruptions in a variety of organisms, including humans. Both γ-aminobutyric acid and dopamine neurons appear to be more vulnerable to MZ exposure than other neuronal populations. Based on these observations, we hypothesized that MZ may be differentially transported into these cells through their presynaptic neurotransmitter transporters. To test this, we pretreated Caenorhabditis elegans with transporter antagonists followed by exposure to various concentrations of MZ...
July 2018: Neurotoxicology and Teratology
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