Embryonic ethanol exposure alters synaptic properties at zebrafish neuromuscular junctions

Sylvain, Nicole J.; Brewster, Daniel L.; Ali, Declan W.

doi:10.1016/j.ntt.2010.12.001

Cited by 21 publications

(14 citation statements)

References 38 publications

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“…These results demonstrate that embryos exposed to ethanol present severe defects in motoneuron axonal branches and correlate with the previous investigations carried out with different ethanol doses [36], [37]. However, several studies suggest different sensitiveness to ethanol of cranial and spinal motoneurons [36], [37], [38].…”

Section: Resultssupporting

confidence: 90%

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Transient Exposure to Ethanol during Zebrafish Embryogenesis Results in Defects in Neuronal Differentiation: An Alternative Model System to Study FASD

et al. 2014

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BackgroundThe exposure of the human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the impairment of the development of the central nervous system (CNS). In spite of the importance for human health, the molecular basis of prenatal ethanol exposure remains poorly understood, mainly to the difficulty of sample collection. Zebrafish is now emerging as a powerful organism for the modeling and the study of human diseases. In this work, we have assessed the sensitivity of specific subsets of neurons to ethanol exposure during embryogenesis and we have visualized the sensitive embryonic developmental periods for specific neuronal groups by the use of different transgenic zebrafish lines.Methodology/Principal FindingsIn order to evaluate the teratogenic effects of acute ethanol exposure, we exposed zebrafish embryos to ethanol in a given time window and analyzed the effects in neurogenesis, neuronal differentiation and brain patterning. Zebrafish larvae exposed to ethanol displayed small eyes and/or a reduction of the body length, phenotypical features similar to the observed in children with prenatal exposure to ethanol. When neuronal populations were analyzed, we observed a clear reduction in the number of differentiated neurons in the spinal cord upon ethanol exposure. There was a decrease in the population of sensory neurons mainly due to a decrease in cell proliferation and subsequent apoptosis during neuronal differentiation, with no effect in motoneuron specification.ConclusionOur investigation highlights that transient exposure to ethanol during early embryonic development affects neuronal differentiation although does not result in defects in early neurogenesis. These results establish the use of zebrafish embryos as an alternative research model to elucidate the molecular mechanism(s) of ethanol-induced developmental toxicity at very early stages of embryonic development.

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Section: Resultssupporting

confidence: 90%

“…However, several studies suggest different sensitiveness to ethanol of cranial and spinal motoneurons [36], [37], [38]. Using other animal models, some authors have shown that ethanol exposure during gestation causes a significant loss of motoneurons and a reduction of motoneuron diameter [39].…”

Section: Resultsmentioning

confidence: 99%

Transient Exposure to Ethanol during Zebrafish Embryogenesis Results in Defects in Neuronal Differentiation: An Alternative Model System to Study FASD

et al. 2014

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“…Motor neuron development is a more sensitive indicator of neurotoxicity than the morphological end points used in early zebrafish embryos (Sylvain et al, 2010(Sylvain et al, , 2011. We took advantage of the transgenic (hb9:GFP) line that makes motor neurons visible in vivo.…”

Section: Discussionmentioning

confidence: 99%

Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

Cuevas

Trickler

Guo

et al. 2013

Neurotoxicology and Teratology

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Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) type glutamate receptors is commonly used as a pediatric anesthetic. Multiple studies have shown ketamine to be neurotoxic, particularly when administered during the brain growth spurt. Previously, we have shown that ketamine is detrimental to motor neuron development in the zebrafish embryos. Here, using both wild type (WT) and transgenic (hb9:GFP) zebrafish embryos, we demonstrate that ketamine is neurotoxic to both motor and sensory neurons. Drug absorption studies showed that in the WT embryos, ketamine accumulation was approximately 0.4% of the original dose added to the exposure medium. The transgenic embryos express green fluorescent protein (GFP) localized in the motor neurons making them ideal for evaluating motor neuron development and toxicities in vivo. The hb9:GFP zebrafish embryos (28 h post fertilization) treated with 2 mM ketamine for 20 h demonstrated significant reductions in spinal motor neuron numbers, while co-treatment with acetyl L-carnitine proved to be neuroprotective. In whole mount immunohistochemical studies using WT embryos, a similar effect was observed for the primary sensory neurons. In the ketamine-treated WT embryos, the number of primary sensory Rohon-Beard (RB) neurons was significantly reduced compared to that in controls. However, acetyl L-carnitine co-treatment prevented ketamine-induced adverse effects on the RB neurons. These results suggest that acetyl L-carnitine protects both motor and sensory neurons from ketamine-induced neurotoxicity.

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“…However, there are no published studies reporting the VPA effects on miRNA expression in in vivo developmental model systems. To test the hypothesis that VPA can alter miRNA expression during development, we used zebrafish embryos, a well established model for studying vertebrate development and developmental toxicity (de Esch et al, 2012; Levin et al, 2003; Levin et al, 2011; Linney et al, 2004; Scalzo and Levin, 2004; Selderslaghs et al, 2013; Sylvain et al, 2011; Tal and Tanguay, 2012). We exposed zebrafish embryos to VPA and quantified the miRNA expression patterns at two different time points, prior to and after the onset of developmental phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Developmental exposure to valproic acid alters the expression of microRNAs involved in neurodevelopment in zebrafish

Aluru

Deak

Jenny

et al. 2013

Neurotoxicology and Teratology

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Congenital malformations are a prevalent cause of infant mortality in the United States and their induction has been linked to a variety of factors, including exposure to teratogens. However, the molecular mechanisms of teratogenicity are not fully understood. MicroRNAs are an important group of small, non-coding RNAs that regulate mRNA expression. MicroRNA roles in early embryonic development are well established, and their disruption during development can cause abnormalities. We hypothesized that developmental exposure to teratogens such as valproic acid alters microRNA expression profiles in developing embryos. Valproic acid is an anticonvulsant and mood-stabilizing drug used to treat epilepsy, bipolar disorder and migraines. To examine the effects of valproic acid on microRNA expression during development, we used zebrafish embryos as a model vertebrate developmental system. Zebrafish embryos were continuously exposed to valproic acid (1 mM) or vehicle control (ethanol) starting from 4 hours post-fertilization (hpf) and sampled at 48 and 96 hpf to determine the miRNA expression profiles prior to and after the onset of developmental defects. At 96 hpf, 95% of the larvae showed skeletal deformities, abnormal swimming behavior, and pericardial effusion. Microarray expression profiling was done using Agilent zebrafish miRNA microarrays. Microarray results revealed changes in miRNA expression at both time points. Thirteen miRNAs were differentially expressed at 48 hpf and 22 miRNAs were altered at 96 hpf. Among them, six miRNAs (miR-16a, 18c, 122, 132, 457b, and 724) were common to both time points. Bioinformatic target prediction and examination of published literature revealed that these miRNAs target several genes involved in the normal functioning of the central nervous system. These results suggest that the teratogenic effects of valproic acid could involve altered miRNA expression.

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Embryonic ethanol exposure alters synaptic properties at zebrafish neuromuscular junctions

Cited by 21 publications

References 38 publications

Transient Exposure to Ethanol during Zebrafish Embryogenesis Results in Defects in Neuronal Differentiation: An Alternative Model System to Study FASD

Transient Exposure to Ethanol during Zebrafish Embryogenesis Results in Defects in Neuronal Differentiation: An Alternative Model System to Study FASD

Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

Developmental exposure to valproic acid alters the expression of microRNAs involved in neurodevelopment in zebrafish

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