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Neurotoxicology and Teratology

Robyn M Amos-Kroohs, Laurie L Davenport, Nina Atanasova, Zuhair I Abdulla, Matthew R Skelton, Charles V Vorhees, Michael T Williams
Manganese (Mn) is an essential element but neurotoxic at higher exposure levels. The effects of Mn overexposure (MnOE) on hippocampal and striatal-dependent learning and memory in rats were tested in combination with iron deficiency (FeD) and developmental stress that often co-occur with MnOE. Moderate FeD affects up to 15% of U.S. children and developmental stress is common in lower socio-economic areas where MnOE occurs. Pregnant Sprague-Dawley rats and their litters were housed in cages with or without (barren cage (BAR)) standard bedding from embryonic day (E)7 to postnatal day (P)28...
October 15, 2016: Neurotoxicology and Teratology
Eunchai Kang, Daniel A Berg, Orion Furmanski, William M Jackson, Yun Kyoung Ryu, Christy D Gray, C David Mintz
The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure...
October 14, 2016: Neurotoxicology and Teratology
Christina R Tyler, Matthew T Labrecque, Elizabeth R Solomon, Xun Guo, Andrea M Allan
Exposure to arsenic, a common environmental toxin found in drinking water, leads to a host of neurological pathologies. We have previously demonstrated that developmental exposure to a low level of arsenic (50ppb) alters epigenetic processes that underlie deficits in adult hippocampal neurogenesis leading to aberrant behavior. It is unclear if arsenic impacts the programming and regulation of embryonic neurogenesis during development when exposure occurs. The master negative regulator of neural-lineage, REST/NRSF, controls the precise timing of fate specification and differentiation of neural stem cells (NSCs)...
October 14, 2016: Neurotoxicology and Teratology
Jacques P Maurissen, Thomas J Vidmar
Repeated-measure analysis of variance is a general term that can imply a number of different statistical models used to analyze data from studies in which measurements are taken from each subject on more than one occasion. Repeated-measure analyses encompass univariate models (with or without sphericity adjustment), multivariate models, mixed models, analysis of covariance, multilevel models, latent growth models, and hybrids of these models. These models are based on different assumptions, especially regarding correlations (sphericity) between within-subject factors, which comprise the variance-covariance matrix...
October 13, 2016: Neurotoxicology and Teratology
Paula Moyano, Javier Del Pino, María José Anadon, María Jesús Díaz, Gloria Gómez, María Teresa Frejo
Chlorpyrifos (CPF) is an organophosphate insecticide reported to induce, both after acute and repeated exposure, learning and memory dysfunctions, although the mechanism is not completely known. CPF produces basal forebrain cholinergic neuronal loss, involved on learning and memory regulation, which could be the cause of such cognitive disorders. This effect was reported to be induced through apoptotic process, partially mediated by AChE overexpression, although neuronal necrosis was also described after CPF exposure...
October 10, 2016: Neurotoxicology and Teratology
Diana Dow-Edwards, Ashley Frank, Wade, Jeremy Weedon, Sari Izenwasser
Recent research has demonstrated that the endogenous cannabinoid system is central to the brain's response to stress. As part of an ongoing collaboration, we sought to examine the effects of prenatal and early postnatal rearing and housing conditions on developing endocannabinoid systems. We compare brain cannabinoid receptors (CBR) in offspring of either prenatal vehicle intubated or non-treated dams (Experiment 1) or in rats derived from a vendor and shipped at weaning to a collaborating lab (Experiment 2)...
September 12, 2016: Neurotoxicology and Teratology
Lianyan Huang, Scott Hayes, Guang Yang
Anesthetic agents are often administered in the neonatal period, a time of rapid brain development and synaptogenesis. Mounting evidence suggests that anesthetics can disrupt neurocognitive development, particularly in cases of multiple or prolonged anesthetic exposure. Previous studies have shown that administering multiple doses of ketamine-xylazine (KX) anesthesia to neonatal mice can induce long-term changes to synaptic plasticity in the cortex, but the effect on neurocognitive function remains unclear...
September 10, 2016: Neurotoxicology and Teratology
Richard J Levy
The majority of commonly used anesthetic agents induce widespread neuronal degeneration in the developing mammalian brain. Downstream, the process appears to involve activation of the oxidative stress-associated mitochondrial apoptosis pathway. Targeting this pathway could result in prevention of anesthetic toxicity in the immature brain. Carbon monoxide (CO) is a gas that exerts biological activity in the developing brain and low dose exposures have the potential to provide neuroprotection. In recent work, low concentration CO exposures limited isoflurane-induced neuronal apoptosis in a dose-dependent manner in newborn mice and modulated oxidative stress within forebrain mitochondria...
September 9, 2016: Neurotoxicology and Teratology
Kimberlei A Richardson, Allison K Hester, Gabrielle L McLemore
As more states and countries legalize medical and/or adult recreational marijuana use, the incidences of Prenatal Cannabis Exposure (PCE) will likely increase. While young people increasingly view marijuana as innocuous, marijuana preparations have been growing in potency in recent years, potentially creating global clinical, public health, and workforce concerns. Unlike fetal alcohol spectrum disorder, there is no phenotypic syndrome associated with PCE. There is also no preponderance of evidence that PCE causes lifelong cognitive, behavioral, or functional abnormalities, and/or susceptibility to subsequent addiction...
August 24, 2016: Neurotoxicology and Teratology
Joanna Jacobus, Norma Castro, Lindsay M Squeglia, M J Meloy, Ty Brumback, Marilyn A Huestis, Susan F Tapert
Cortical thickness abnormalities have been identified in youth using both alcohol and marijuana. However, limited studies have followed individuals pre- and post initiation of alcohol and marijuana use to help identify to what extent discrepancies in structural brain integrity are pre-existing or substance-related. Adolescents (N=69) were followed from ages 13 (pre-initiation of substance use, baseline) to ages 19 (post-initiation, follow-up). Three subgroups were identified, participants that initiated alcohol use (ALC, n=23, >20 alcohol use episodes), those that initiated both alcohol and marijuana use (ALC+MJ, n=23, >50 marijuana use episodes) and individuals that did not initiate either substance regularly by follow-up (CON, n=23, <3 alcohol use episodes, no marijuana use episodes)...
September 2016: Neurotoxicology and Teratology
Eileen M Moore, M Alejandra Infante, Robyn Migliorini, Sarah N Mattson, Edward P Riley
Prenatal alcohol exposure can interfere with endocrine function and have sex-specific effects on behavior. Disrupted development of the pituitary gland, which has been observed in rodent studies, may account for some of these effects. To determine if gestational exposure to alcohol produces measureable changes in the pituitary in human adolescents, we manually traced the pituitary in T1-weighted structural magnetic resonance images (MRI) from adolescents with (15 males, 11 females) and without (16 males, 11 females) heavy prenatal alcohol exposure...
September 2016: Neurotoxicology and Teratology
Charles V Vorhees, Michael T Williams
Advantageous maneuvering through the environment to find food and avoid or escape danger is central to survival of most animal species. The ability to do so depends on learning and remembering different locations, especially home-base. This capacity is encoded in the brain by two systems: one using cues outside the organism (distal cues), allocentric navigation, and one using self-movement, internal cues (proximal cues), for egocentric navigation. Whereas allocentric navigation involves the hippocampus, entorhinal cortex, and surrounding structures, egocentric navigation involves the dorsal striatum and connected structures; in humans this system encodes routes and integrated paths and when over-learned, becomes procedural memory...
September 2016: Neurotoxicology and Teratology
Peter F Cook, Colleen Reichmuth, Andrew Rouse, Sophie Dennison, Bill Van Bonn, Frances Gulland
Domoic acid is a naturally occurring algal toxin that causes neurological symptoms and mortality in exposed marine life. California sea lions (Zalophus californianus) are the most visible victims, and suffer epilepsy and progressive hippocampal atrophy. Despite its reliable neurological effects, little is known about how exposure to domoic acid alters behavior, which is critical for understanding the impact of toxic exposure on long-term survival in sea lions and other exposed animals, including humans. Better understanding of the behavioral effects may also inform veterinary diagnosis and treatment...
September 2016: Neurotoxicology and Teratology
Stephanie A Godleski, Rina D Eiden, Pamela Schuetze, Craig R Colder, Marilyn A Huestis
Prenatal exposure to tobacco has consistently predicted later problem behavior for children. However, little is known about developmental mechanisms underlying this association. We examined a conceptual model for the association between prenatal tobacco exposure and child problem behavior in toddlerhood via indirect paths through fetal growth, maternal depression, and maternal aggressive disposition in early infancy and via maternal warmth and sensitivity and infant negative affect in later infancy. The sample consisted of 258 mother-child dyads recruited during pregnancy and assessed periodically at 2, 9, and 16months of child age...
September 2016: Neurotoxicology and Teratology
Sonia Minnes, Meeyoung O Min, Elizabeth J Short, Miaoping Wu, Adelaide Lang, Susan Yoon, Lynn T Singer
PURPOSE: Prenatal exposure to cocaine (PCE) may alter areas of the brain dense with monoamine receptors such as the prefrontal cortex and negatively affect cognitive processes implicated in executive function (EF). This study investigated the effects of PCE on EF at 12 and 15years. METHODS: EF was examined in 189 PCE and 183 non-cocaine exposed (NCE) children who were primarily African American and of low socioeconomic status. Caregivers rated their child on the Behavior Rating Inventory of Executive Function (BRIEF) at ages 12 and 15...
September 2016: Neurotoxicology and Teratology
Emily Oken, Sheryl L Rifas-Shiman, Chitra Amarasiriwardena, Innocent Jayawardene, David C Bellinger, Joseph R Hibbeln, Robert O Wright, Matthew W Gillman
BACKGROUND: Few studies of maternal prenatal fish intake have included biomarkers of exposure to mercury, long-chain n-3 fatty acids, and selenium, which are hypothesized to mediate associations with child neurodevelopment. OBJECTIVES: Examine associations of maternal prenatal fish intake with child neurodevelopment accounting for biomarkers. METHODS: In 1999-2002 we enrolled pregnant women into the Project Viva cohort.At median 27.9weeks gestation, we estimated maternal fish intake using food frequency questionnaires, and collected blood...
July 2, 2016: Neurotoxicology and Teratology
X Zhang, G D Newport, R Callicott, S Liu, J Thompson, M S Berridge, S M Apana, W Slikker, C Wang, M G Paule
Methylphenidate (MPH) is a psychostimulant commonly used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Since the long-term effects of this drug on the central nervous system (CNS) are not well understood, we conducted microPET/CT scans on young adult male rhesus monkeys (n=4/group) to gather information on brain metabolism using the uptake of [(18)F]Fluoro-2-deoxy-2-d-glucose (FDG) as a marker. Approximately two-year old, male rhesus monkeys were treated orally with MPH twice per day, five days per week (M-F) over a 6-year period...
July 2016: Neurotoxicology and Teratology
Robyn M Amos-Kroohs, Laurie L Davenport, Arnold Gutierrez, Jillian R Hufgard, Charles V Vorhees, Michael T Williams
Manganese (Mn) is an essential element but neurotoxic at higher exposures, however, Mn exposure seldom occurs in isolation. It often co-occurs in populations with inadequate dietary iron (Fe) and limited resources that result in stress. Subclinical FeD affects up to 15% of U.S. children and exacerbates Mn toxicity by increasing Mn bioavailability. Therefore, we investigated Mn overexposure (MnOE) in rats in combination with Fe deficiency (FeD) and developmental stress, for which we used barren cage rearing...
July 2016: Neurotoxicology and Teratology
Samantha M Renaud, Stephen B Fountain
This study investigated whether adolescent nicotine exposure in one generation of rats would impair the cognitive capacity of a subsequent generation. Male and female rats in the parental F0 generation were given twice-daily i.p. injections of either 1.0mg/kg nicotine or an equivalent volume of saline for 35days during adolescence on postnatal days 25-59 (P25-59). After reaching adulthood, male and female nicotine-exposed rats were paired for breeding as were male and female saline control rats. Only female offspring were used in this experiment...
July 2016: Neurotoxicology and Teratology
Joel G Hashimoto, Kristine M Wiren, Clare J Wilhelm
Alcohol abuse is associated with neurological dysfunction, brain morphological deficits and frank neurotoxicity. Although these disruptions may be a secondary effect due to hepatic encephalopathy, no clear evidence of causality is available. This study examined whether a 72h period of alcohol intoxication known to induce physical dependence, followed by a single withdrawal, was sufficient to induce signs of hepatic encephalopathy in male and female mice. Animals were continuously intoxicated via alcohol vapor inhalation, a procedure previously shown to induce significant neurotoxicity in female mice...
July 2016: Neurotoxicology and Teratology
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