Neurotoxicology and Teratology

Buspirone is a pharmaceutical used to treat general anxiety disorder by acting on the dopaminergic 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 behavior of zebrafish, focusing on locomotor and anxiolytic behavior. We also measured transcripts associated with oxidative stress, neurotoxicity, and serotonin signaling to identify potential mechanisms underlying and behavioral changes...

Valproic acid (VPA) is an anti-epileptic medication that increases the risk of neural tube defect (NTD) outcomes in infants exposed during gestation. Previous studies into VPA's mechanism of action have focused on alterations in gene expression and metabolism but have failed to consider how exposure changes the abundance of critical developmental proteins over time. This study evaluates the effects of VPA on protein abundance in the developmentally distinct tissues of the mouse visceral yolk sac (VYS) and embryo proper (EMB) using mouse whole embryo culture...

INTRODUCTION: Many studies have examined changes in marijuana use across adolescence, but few have examined factors associated with transitions from adolescence to young adulthood. We examined prenatal exposures to alcohol and marijuana and adolescent risk and protective factors that best distinguished among abstinence, continuity, or cessation of marijuana use from 16 to 22 years. METHOD: Data were from the Maternal Health Practices and Child Development Project at the prenatal and 16- and 22-year follow-up phases...

Paracetamol (PAR) is an over-the-counter analgesic/antipyretic used during pregnancy worldwide. Epidemiological studies have been associating gestational PAR exposure with neurobehavioral alterations in the progeny resembling autism spectrum disorders and attention-deficit hyperactivity disorder symptoms. The endocannabinoid (eCB) dysfunction was previously hypothesized as one of the modes of action by which PAR may harm the developing nervous system. We aimed to evaluate possible effects of gestational exposure to PAR on male and female rat's offspring behavior and if an acute injection of WIN 55,212-2 (WIN, 0...

Zebrafish are frequently used as a vertebrate model to elucidate toxicological and pharmacological mechanisms of action in the central nervous system. Pharmacological studies demonstrate that dopamine, signaling via several receptor subtypes, regulates zebrafish larval behavior. Quinpirole is a selective dopamine receptor agonist for D2 and D3 subtypes while ropinirole exhibits selectivity toward D2, D3, and D4 receptors. The main objective of this study was to determine the short-term actions of quinpirole and ropinirole on the locomotor activity and anxiolytic/anti-anxiolytic behaviors of zebrafish...

BACKGROUND: Exposure to perfluoroalkyl substances (PFAS) has been shown to be neurotoxic in experimental studies, but epidemiological evidence linking prenatal PFAS exposure to child neurodevelopment is equivocal and scarce. OBJECTIVE: To quantify associations between prenatal exposure to legacy PFAS and children's intelligence (IQ) and executive functioning (EF) in a Canadian pregnancy and birth cohort and to determine if these associations differ by child sex...

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to a wide array of adverse maternal and child health outcomes. However, studies examining PFAS in relation to offspring cognition have been inconclusive. OBJECTIVE: We examined whether prenatal exposure to a mixture of PFAS was related to cognition in 7.5-month-old infants. METHODS: Our analytic sample included participants enrolled in the Chemicals in Our Bodies (CIOB) and Illinois Kids Development Study (IKIDS) cohorts (N = 163)...

Several studies have begun to demonstrate the possible cognitive and physiological benefits of a fortified vitamin D diet. However, the behavioral effects of a high vitamin D fortified diet during adolescence has not been fully explored. In the present study, a 4-week vitamin D fortified diet (20,000 IU/Kg) compared to controls (1500 IU/Kg) was administered during the juvenile (4 weeks old) or early adult period (8 weeks old) in C57BL/6 J mice to investigate the effects of fortification on cognition, behavior, and their bone phenotype...

BACKGROUND: Prenatal opioid exposure has been associated with developmental deficits during infancy, but the literature is limited by simple group comparisons and lack of appropriate controls. Previously published research with the current sample documented unique associations between prenatal opioid exposure and developmental outcomes at three and six months, but less is known about associations later in infancy. METHOD: The current study examined pre- and postnatal opioid and polysubstance exposure as predictors of parent-reported developmental status at 12 months of age...

Nicotine exposure is associated with negative consequences on the developing brain, both in utero and after birth. We investigated the relationship between perinatal nicotine exposure and electroencephalographic brain activity recorded during an emotional faces Go/No-Go task among adolescents. Seventy-one adolescents aged 12-15 years completed a Go/No-Go task using fearful and happy faces. Parents completed questionnaire measures of their child's temperament and self-regulation and retrospectively reported on nicotine exposure during the perinatal period...

Per- and polyfluoroalkyl substances (PFAS) cause potential threats to biota and are persistent and never-ending substances in the environment. Regulations and ban on legacy PFAS by various global organizations and national level regulatory agencies had shifted the fluorochemical production to emerging PFAS and fluorinated alternatives. Emerging PFAS are mobile and more persistent in aquatic systems, posing potential greater threats to human and environmental health. Emerging PFAS have been found in aquatic animals, rivers, food products, aqueous film-forming foams, sediments, and a variety of other ecological media...

Per- and polyfluoroalkyl substances (PFAS) are commonly used as surfactants and coatings for industrial processes and consumer products. These compounds have been increasingly detected in drinking water and human tissue, and concern over their potential effects on health and development is growing. However, relatively little data are available for their potential impacts on neurodevelopment and the degree to which different compounds within this class may differ from one another in their neurotoxicity. The present study examined the neurobehavioral toxicology of two representative compounds in a zebrafish model...

In nature, cold stress is a core threat to aquatic organisms. But the neurodevelopmental effects of cold stress during the perinatal period on the offspring development were unknown. In the present study, adult zebrafish were cold-stressed at 18 °C for five days before spawning, and then the fertilized eggs were raised at 18, 24, or 28 °C from 0 to 120 h post fertilization (hpf). The resulting embryos and larvae were assessed for developmental and neurobehavioral responses. Our findings showed that embryos raised at 18 °C (Cold+++) suffered hatching failure and death, at 24 °C (Cold++) had decreased hatching, while those raised at 28 °C (Cold+) exhibited no developmental adversity...

New approaches in developmental neurotoxicity (DNT) screening are needed due to the tens of thousands of chemicals requiring hazard assessments. Zebrafish (Danio rerio) are an alternative vertebrate model for DNT testing, but without a standardized protocol for larval behavioral assays, comparison of results among laboratories is challenging. To evaluate the congruence of protocols across laboratories, we conducted a literature review of DNT studies focusing on larval zebrafish behavior assays and cataloged experimental design consistencies...

One in four Americans have used cannabidiol (CBD) products in the past year, and use has become prevalent in many Western countries with recent deregulation from a controlled or illicit substance to an unrestricted product. CBD is also marketed to pregnant people to treat common medical conditions. However, preclinical work has linked cannabidiol exposure to embryotoxicity, as well as neuroendocrine, reproductive, and behavioral effects in offspring. No studies have examined the prevalence or correlates of CBD use among pregnant people...

BACKGROUND: Phthalates are endocrine disrupters used in a variety of consumer products. Human studies suggest an association between phthalate exposure and cognitive development but adverse effects of the recently introduced phthalate substitutes have only been sparsely studied. OBJECTIVES: To investigate associations between prenatal and concurrent exposure to phthalates and IQ in 7-year-old children from the Odense Child Cohort. METHODS: Pregnant women from the Odense Child Cohort had phthalate metabolites measured in urine samples during 3rd trimester in 2010 to 2012...

Effects of prenatal bisphenol A (BPA) exposure on child behavior are mixed with some reports suggesting increased problematic behaviors in girls (e.g., aggression and emotional reactivity) and in boys (i.e., externalizing behaviors), while other reports suggest decreased problematic behaviors in girls. Little is known about the potential impact of pregnancy bisphenol S (BPS) exposure on child behavior. In a prospective cohort study (n = 68), five maternal spot urine samples collected across pregnancy were pooled and analyzed for BPA and BPS...

OBJECTIVE: Prenatal cocaine exposure (PCE) has been linked to specific cognitive deficits and behavioral outcomes through early adolescence but there is little information on adult outcomes nor on the relationship of environmental interventions, such as foster/adoptive care, to outcomes. METHODS: At 21 years, data were available on 325 young adults, [163 PCE and 162 non-exposed (NCE)], primarily African-American, with low SES, who were followed from birth in a prospective longitudinal cohort study...

Prenatal stress adversely affects offspring 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 amniotic fluid. However, in humans, 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 N = 18 healthy rhesus macaque (Macaca mulatta) dams (50:50 female:male infants) between 80 and 124 days gestation (mean ± SEM = 98...

BACKGROUND: 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. METHODS: 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...