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Developmental Exposure (developmental + exposure)

Distribution by Scientific Domains

Life Sciences	62%

Selected Abstracts

Structural and Functional Effects of Developmental Exposure to Ethanol on the Zebrafish Heart

ALCOHOLISM, Issue 6 2010
Cynthia A. Dlugos
Background:, Fetal alcohol exposure during development results in a host of cardiac abnormalities including atrial and ventricular septal defects, teratology of Fallot, d-transposition of the great arteries, truncus arteriosus communis, and aortico-pulmonary window. The mechanisms behind these ethanol-induced deficits are unknown. The purpose of this study was to determine whether the zebrafish, a simple model in which heart development and the sequence of gene expression is well elucidated and comparable to that in higher vertebrates, is sensitive to developmental exposure of pharmacologically relevant concentrations of ethanol. Methods:, Zebrafish eggs of the AB strain were raised in egg water or in 0.5% (v/v) ethanol solution for either 54 hpf (hours postfertilization) or 72 hpf. Heart pathology and volumes were evaluated on the latter group at 5 dpf (days postfertilization) on tissue sections from fixed larvae embedded in glycolmethacrylate. Heart rates were determined in embryos of 54 hpf and larvae of 5 dpf. The functional maturity of the heart's conducting system was measured by determining the response of ethanol-treated and control embryos and larvae to the adrenergic agonist, isoproterenol, and the cholinergic agonist, carbachol. Results:, Ethanol-induced alterations occurred in heart morphology and heart volume. A developmental lag in the isoproterenol response and the absence of carbachol-mediated bradycardia were also observed following ethanol treatment. Conclusions:, These results show that exposure of the zebrafish to ethanol during development results in structural and functional changes in the heart that mimic malformations that occur in patients with fetal alcohol syndrome (FAS). These findings promote the zebrafish heart as a future model for investigating the mechanisms responsible for ethanol's adverse effects on vertebrate heart development. [source]

Long-Term Behavioral Changes in Response to Early Developmental Exposure to Ethanol in Zebrafish

ALCOHOLISM, Issue 4 2009
Yohaan Fernandes
Background:, Zebrafish is becoming an important research tool for the analysis of brain function and behavior. It has been proposed to model human alcoholism as well as fetal alcohol syndrome. Previous studies investigating the consequences of exposure to ethanol during early development of zebrafish employed robust dosing regimens (high ethanol concentration and long exposure) that may model a rare situation in the human clinic. These studies found major structural abnormalities developing in the exposed fish. Methods: Here we hope to avoid such gross changes and administer only low doses of ethanol (0.00, 0.25, 0.50, 0.75, 1.00 vol/vol %) at 24-hour postfertilization and for only a short period of time (for 2 hours). We analyze the behavior of exposed fish at adult stage using computerized stimulus presentation and automated videotracking response quantification. Results: Despite the short ethanol exposure period and the modest concentrations, significant behavioral alterations were found: fish exposed to higher doses of ethanol swam at an increased distance from a computer-animated zebrafish shoal while their activity levels did not change. Conclusions: Although the interpretation of and the mechanisms underlying this finding will require further investigation, the results suggest that zebrafish will be an appropriate model organism for the analysis of the effects of moderate to mild prenatal ethanol exposure. [source]

Elevated corticosterone levels in stomach milk, serum, and brain of male and female offspring after maternal corticosterone treatment in the rat

DEVELOPMENTAL NEUROBIOLOGY, Issue 10 2010
Susanne Brummelte
Abstract Early influences such as maternal stress affect the developmental outcome of the offspring. We created an animal model of postpartum depression/stress based on giving high levels of corticosterone (CORT) to the rat dam, which resulted in behavioral and neural changes in the offspring. This study investigated whether highly elevated levels of maternal CORT during pregnancy or the postpartum result in higher levels of CORT in the stomach milk, serum, and brain of offspring. Dams received daily injections of CORT (40 mg/kg) or oil (control) either during pregnancy (gestational days 10,20) or the postpartum (Days 2,21). Pups that were exposed to high gestational maternal CORT had higher CORT levels in serum, but not in stomach milk or brain, on postnatal day (PND) 1. However, on PND7, pups that were exposed to high postpartum maternal CORT had higher CORT levels in stomach milk and brain, but not in serum. Conversely on PND18, pups that were exposed to high postpartum maternal CORT had higher CORT levels in serum, but not in brain (prefrontal cortex, hypothalamus, or hippocampus). Moreover, 24 h after weaning, there were no significant differences in serum CORT levels between the groups. Thus, CORT given to the dam during pregnancy or the postpartum results in elevated levels of CORT in the offspring, but in an age- and tissue-dependent manner. Developmental exposure to high CORT could reprogram the HPA axis and contribute to the behavioral and neural changes seen in adult offspring. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 714,725, 2010 [source]

Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome,

DEVELOPMENTAL DYNAMICS, Issue 2 2007
Maia L. Green
Abstract Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from maternal alcohol use. We used a non a priori approach to prioritize candidate pathways during alcohol-induced teratogenicity in early mouse embryos. Two C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams with alcohol (2× 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter-exposure to PK11195 (4 mg/kg) significantly protected B6J embryos but slightly promoted FASD in B6N embryos. Microarray transcript profiling was performed on the embryonic headfold 3 hr after the first maternal alcohol injection (GEO data series accession GSE1074). This analysis revealed metabolic and cellular reprogramming that was substrain-specific and/or PK11195-dependent. Mapping ethanol-responsive KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed down-regulation of ribosomal proteins and proteasome, and up-regulation of glycolysis and pentose phosphate pathway in B6N embryos; and significant up-regulation of tight junction, focal adhesion, adherens junction, and regulation of the actin cytoskeleton (and near-significant up-regulation of Wnt signaling and apoptosis) pathways in both substrains. Expression networks constructed computationally from these altered genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14, PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are consistent with the growing view that developmental exposure to alcohol alters common signaling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195. Developmental Dynamics 236:613,631, 2007. © 2007 Wiley-Liss, Inc. [source]

Developmental experience alters information coding in auditory midbrain and forebrain neurons

DEVELOPMENTAL NEUROBIOLOGY, Issue 4 2010
Sarah M.N. Woolley
Abstract In songbirds, species identity and developmental experience shape vocal behavior and behavioral responses to vocalizations. The interaction of species identity and developmental experience may also shape the coding properties of sensory neurons. We tested whether responses of auditory midbrain and forebrain neurons to songs differed between species and between groups of conspecific birds with different developmental exposure to song. We also compared responses of individual neurons to conspecific and heterospecific songs. Zebra and Bengalese finches that were raised and tutored by conspecific birds, and zebra finches that were cross-tutored by Bengalese finches were studied. Single-unit responses to zebra and Bengalese finch songs were recorded and analyzed by calculating mutual information (MI), response reliability, mean spike rate, fluctuations in time-varying spike rate, distributions of time-varying spike rates, and neural discrimination of individual songs. MI quantifies a response's capacity to encode information about a stimulus. In midbrain and forebrain neurons, MI was significantly higher in normal zebra finch neurons than in Bengalese finch and cross-tutored zebra finch neurons, but not between Bengalese finch and cross-tutored zebra finch neurons. Information rate differences were largely due to spike rate differences. MI did not differ between responses to conspecific and heterospecific songs. Therefore, neurons from normal zebra finches encoded more information about songs than did neurons from other birds, but conspecific and heterospecific songs were encoded equally. Neural discrimination of songs and MI were highly correlated. Results demonstrate that developmental exposure to vocalizations shapes the information coding properties of songbird auditory neurons. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 70: 235,252, 2010. [source]

Structural and Functional Effects of Developmental Exposure to Ethanol on the Zebrafish Heart

Nutritional, developmental, and genetic influences on relative sitting height at high altitude,

AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2009
Sara Stinson
The study explores how nutritional status, developmental exposure to high-altitude hypoxia, and genetic ancestry influence relative sitting height in two groups of high-altitude Bolivian children aged 8 through 13 years of age: 253 rural Aymara children of very low socioeconomic status and 273 children of upper socioeconomic status from the capital city of La Paz. The rural Aymara children on average have longer trunks relative to stature, but there is also overlap in body proportions between the two groups of children. The 20% of each sample in the region of overlap was examined to investigate influences on relative sitting height. Nutritional effects on relative sitting height are suggested by the finding that Aymara children with relatively long legs are taller, heavier, and fatter than other Aymara children. Developmental and genetic influences on relative sitting height are suggested by the finding that high relative sitting heights in elite urban children are associated with a greater percentage of time lived at high altitude and with parents born in Bolivia. Separating developmental and ancestry effects is difficult because the two are closely interconnected in the urban children. The results of this study suggest that influences on growth in relative trunk and leg length are similar to those that affect other aspects of growth in Andean populations. They also highlight the fact that because relative sitting height gradually decreases prior to adolescence and then increases, the interpretation of variation in body proportions in children is not always straightforward. Am. J. Hum. Biol. 2009. © 2009 Wiley-Liss, Inc. [source]