Ethanol exposure during embryogenesis decreases the radial glial progenitorpool and affects the generation of neurons and astrocytes

Rubert, Gemma; Miñana, Rosa; Pascual, Marı́a; Guerri, Consuelo

doi:10.1002/jnr.20963

Cited by 82 publications

(61 citation statements)

References 45 publications

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“…The apparent resilience of the adult NSC pool to in vivo alcohol exposure contrasts in some respects with recent findings indicating that prenatal alcohol reduces the number of neurospheres in the neonatal SVZ (Akers et al, 2011; Rubert et al, 2006; Santillano et al, 2005). NSCs may be more sensitive to insults during embryonic expansion of the pool relative to the static population dynamics of adulthood, as has been demonstrated for other insults such as prenatal versus adult stress (Kippin et al, 2004).…”

Section: Discussioncontrasting

confidence: 85%

Alcohol exposure inhibits adult neural stem cell proliferation

et al. 2014

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Alcohol exposure can reduce adult proliferation and/or neurogenesis, but its impact on the ultimate neurogenic precursors, neural stem cells (NSCs), has been poorly addressed. Accordingly, the impact of voluntary consumption of alcohol on NSCs in the subventricular zone (SVZ) of the lateral ventricle was examined in this study. The NSC population in adult male C57BL/6J mice was measured after voluntary alcohol exposure in a two-bottle choice task using the neurosphere assay, while the number of NSCs that had proliferated two weeks prior to tissue collection was indexed using bromodeoxyuridine (BrdU) retention. There was a significant decrease in the number of BrdU-retaining cells in alcohol consuming mice compared to controls, but no difference in the number of neurosphere-forming cells that could be derived from the SVZ of alcohol consuming mice compared to controls. Additionally, PCNA-labeled cells in the SVZ tended to be lower but there was no difference in BrdU labeling in the dentate gyrus following alcohol exposure. To determine alcohol’s direct impact on NSCs and their progeny, neurospheres derived from naïve mice were treated with alcohol in vitro. Neurosphere formation was reduced by 100 mM alcohol without reducing cell viability. These findings are the first to assess the impact of moderate voluntary alcohol consumption on selective measures of adult NSCs and indicate that such exposure alters NSC proliferation dynamics in vivo and alcohol has direct but dissociable effects on the expansion and viability on NSCs and their progeny in vitro.

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Section: Discussioncontrasting

confidence: 85%

Alcohol exposure inhibits adult neural stem cell proliferation

et al. 2014

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“…Published in vivo studies do show that ethanol can affect the proliferation of progenitor cells (e.g., Miller and Nowakowski, 1991;Miller and Kuhn, 1995;Miller, 1996) and fate decisions (e.g., Kentroti and Vernadakis, 1992). Data from in vitro studies show that the proliferation (Vemuri and Chetty, 2005;Santillano et al, 2006) and decisions of cell lineage (Vemuri and Chetty, 2005;Rubert et al, 2006) of neural stem cells are affected by ethanol.…”

Section: Mechanisms Of Ethanol Toxicitymentioning

confidence: 99%

Time-specific effects of ethanol exposure on cranial nerve nuclei: Gastrulation and neuronogenesis

Mooney

Miller

2007

Experimental Neurology

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During the development of the central nervous system, neurons pass through critical periods or periods of vulnerability. We explored periods of vulnerability for cranial nerve nuclei by determining the effects of acute exposure to ethanol during development on the number of neurons in mature brainstem. Long-Evans rats were injected with 2.9 g ethanol/kg body weight on one day between gestational day (G) 7 and G13, inclusive. Two hours later, animals received a second injection of 1.45 g/kg. Controls were injected with equivalent volumes of saline. Brainstems of 31-day-old offspring were cryosectioned and stained with cresyl violet. Stereological methods were used to determine the volume and numerical density of neurons in three trigeminal sensory nuclei (the principal sensory nucleus of the trigeminal nerve, and the oral and interpolar subnuclei of the spinal trigeminal nuclear complex) and three motor nuclei (the trigeminal, facial, and hypoglossal nuclei). The numbers of neurons in most nuclei were lower following early (on G7 and/or G8) or later (on G12 and/or G13) exposure. Only the trigeminal interpolar nucleus was affected by neither early nor late ethanol exposure. Thus, prenatal exposure to ethanol affects the number of neurons in brainstem nuclei in a time-dependent manner. Windows of vulnerability coincide with gastrulation (G7/G8) and the period of neuronal generation (G12/G13).

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“…Sulfation of heparan sulfate chains of heparan sulfate proteoglycans (HSPGs) is diminished, with concomitant loss of axon-promoting function, in response to ethanol (Dow and Riopelle 1990). Genes encoding ECM proteins that are essential to ECM function and CNS development, such as Fgf2 and Fgf8, are targets of ethanol exposure in prenatal mice (Aoto et al, 2008; Rubert et al, 2006). Sonic hedgehog (Shh) signaling is an apparent key target of prenatal ethanol exposure.…”

Section: Introductionmentioning

confidence: 99%

Agrin function associated with ocular development is a target of ethanol exposure in embryonic zebrafish

Zhang

Turton

Mackinnon

et al. 2011

Birth Defects Research

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BACKGROUND Alcohol (ethanol) is a teratogen known to affect the developing eyes, face and brain. Among the ocular defects in fetal alcohol spectrum disorder (FASD) are microphthalmia and optic nerve hypoplasia. Employing zebrafish as an FASD model provides an excellent system to analyze the molecular basis of prenatal ethanol exposure-induced defects since embryos can be exposed to ethanol at defined developmental stages and affected genetic pathways can be examined. We have previously shown that disruption of agrin function in zebrafish embryos produces microphthalmia and optic nerve hypoplasia. METHODS Zebrafish embryos were exposed to varying concentrations of ethanol in the absence or presence of morpholino oligonucleotides (MOs) that disrupt agrin function. In situ hybridization was employed to analyze ocular gene expression as a consequence of ethanol exposure and agrin knockdown. Morphological analysis of zebrafish embryos was also conducted. RESULTS Acute ethanol exposure induces diminished agrin gene expression in zebrafish eyes and, importantly, combined treatment with subthreshold levels of agrin MO and ethanol produces pronounced microphthalmia, markedly reduces agrin gene expression, and perturbs Pax6a andMbx gene expression. Microphthalmia produced by combined agrin MO and ethanol treatment was rescued by sonic hedgehog (Shh) mRNA overexpression, suggesting that ethanol-mediated disruption of agrin expression results in disrupted Shh function. CONCLUSIONS These studies illustrate the strong potential for using zebrafish as a model to aid in defining the molecular basis for ethanol's teratogenic effects. The results of this work suggest that agrin expression and function may be a target of ethanol exposure during embryogenesis.

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Ethanol exposure during embryogenesis decreases the radial glial progenitorpool and affects the generation of neurons and astrocytes

Cited by 82 publications

References 45 publications

Alcohol exposure inhibits adult neural stem cell proliferation

Alcohol exposure inhibits adult neural stem cell proliferation

Time-specific effects of ethanol exposure on cranial nerve nuclei: Gastrulation and neuronogenesis

Agrin function associated with ocular development is a target of ethanol exposure in embryonic zebrafish

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