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Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density

Jegou et al. (2012) have reported prenatal alcohol exposure (PAE)-induced reductions of angiogenesis-related proteins in mouse placenta. These effects were associated with striking alterations in microvascular development in neonatal cerebral cortex. Here, we employed a rat model of moderate PAE to...

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Autores principales: Savage, Daniel D., Rosenberg, Martina J., Coquet, Laurent, Porch, Morgan W., Allen, Nyika A., Roux, Christian, Aligny, Caroline, Jouenne, Thierry, Gonzalez, Bruno J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325964/
https://www.ncbi.nlm.nih.gov/pubmed/32655346
http://dx.doi.org/10.3389/fnins.2020.00519
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author Savage, Daniel D.
Rosenberg, Martina J.
Coquet, Laurent
Porch, Morgan W.
Allen, Nyika A.
Roux, Christian
Aligny, Caroline
Jouenne, Thierry
Gonzalez, Bruno J.
author_facet Savage, Daniel D.
Rosenberg, Martina J.
Coquet, Laurent
Porch, Morgan W.
Allen, Nyika A.
Roux, Christian
Aligny, Caroline
Jouenne, Thierry
Gonzalez, Bruno J.
author_sort Savage, Daniel D.
collection PubMed
description Jegou et al. (2012) have reported prenatal alcohol exposure (PAE)-induced reductions of angiogenesis-related proteins in mouse placenta. These effects were associated with striking alterations in microvascular development in neonatal cerebral cortex. Here, we employed a rat model of moderate PAE to search for additional proteins whose placental and fetal cortical expression is altered by PAE, along with a subsequent examination of fetal cerebral cortical alterations associated with altered protein expression. Long-Evans rat dams voluntarily consumed either a 0 or 5% ethanol solution 4 h each day throughout gestation. Daily ethanol consumption, which resulted in a mean peak maternal serum ethanol concentration of 60.8 mg/dL, did not affect maternal weight gain, litter size, or placental or fetal body weight. On gestational day 20, rat placental: fetal units were removed by Caesarian section. Placental protein expression, analyzed by 2D-PAGE – tandem mass spectroscopy, identified a total of 1,117 protein spots, 20 of which were significantly altered by PAE. To date, 14 of these PAE-altered proteins have been identified. Western blotting confirmed the alterations of two of these placental proteins, namely, annexin-A4 (ANX-A4) and cerebral cavernous malformation protein 3 (CCM-3). Specifically, PAE elevated ANX-A4 and decreased CCM-3 in placenta. Subsequently, these two proteins were measured in fetal cerebral cortex, along with radiohistochemical studies of VEGF binding and histofluorescence studies of microvascular density in fetal cerebral cortex. PAE elevated ANX-A4 and decreased CCM-3 in fetal cerebral cortex, in a pattern similar to the alterations observed in placenta. Further, both VEGF receptor binding and microvascular density and orientation, measures that are sensitive to reduced CCM-3 expression in developing brain, were significantly reduced in the ventricular zone of fetal cerebral cortex. These results suggest that the expression angiogenesis-related proteins in placenta might serve as a biomarker of ethanol-induced alterations in microvascular development in fetal brain.
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spelling pubmed-73259642020-07-09 Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density Savage, Daniel D. Rosenberg, Martina J. Coquet, Laurent Porch, Morgan W. Allen, Nyika A. Roux, Christian Aligny, Caroline Jouenne, Thierry Gonzalez, Bruno J. Front Neurosci Neuroscience Jegou et al. (2012) have reported prenatal alcohol exposure (PAE)-induced reductions of angiogenesis-related proteins in mouse placenta. These effects were associated with striking alterations in microvascular development in neonatal cerebral cortex. Here, we employed a rat model of moderate PAE to search for additional proteins whose placental and fetal cortical expression is altered by PAE, along with a subsequent examination of fetal cerebral cortical alterations associated with altered protein expression. Long-Evans rat dams voluntarily consumed either a 0 or 5% ethanol solution 4 h each day throughout gestation. Daily ethanol consumption, which resulted in a mean peak maternal serum ethanol concentration of 60.8 mg/dL, did not affect maternal weight gain, litter size, or placental or fetal body weight. On gestational day 20, rat placental: fetal units were removed by Caesarian section. Placental protein expression, analyzed by 2D-PAGE – tandem mass spectroscopy, identified a total of 1,117 protein spots, 20 of which were significantly altered by PAE. To date, 14 of these PAE-altered proteins have been identified. Western blotting confirmed the alterations of two of these placental proteins, namely, annexin-A4 (ANX-A4) and cerebral cavernous malformation protein 3 (CCM-3). Specifically, PAE elevated ANX-A4 and decreased CCM-3 in placenta. Subsequently, these two proteins were measured in fetal cerebral cortex, along with radiohistochemical studies of VEGF binding and histofluorescence studies of microvascular density in fetal cerebral cortex. PAE elevated ANX-A4 and decreased CCM-3 in fetal cerebral cortex, in a pattern similar to the alterations observed in placenta. Further, both VEGF receptor binding and microvascular density and orientation, measures that are sensitive to reduced CCM-3 expression in developing brain, were significantly reduced in the ventricular zone of fetal cerebral cortex. These results suggest that the expression angiogenesis-related proteins in placenta might serve as a biomarker of ethanol-induced alterations in microvascular development in fetal brain. Frontiers Media S.A. 2020-06-03 /pmc/articles/PMC7325964/ /pubmed/32655346 http://dx.doi.org/10.3389/fnins.2020.00519 Text en Copyright © 2020 Savage, Rosenberg, Coquet, Porch, Allen, Roux, Aligny, Jouenne and Gonzalez. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Savage, Daniel D.
Rosenberg, Martina J.
Coquet, Laurent
Porch, Morgan W.
Allen, Nyika A.
Roux, Christian
Aligny, Caroline
Jouenne, Thierry
Gonzalez, Bruno J.
Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density
title Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density
title_full Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density
title_fullStr Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density
title_full_unstemmed Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density
title_short Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density
title_sort ethanol-induced alterations in placental and fetal cerebrocortical annexin-a4 and cerebral cavernous malformation protein 3 are associated with reductions in fetal cortical vegf receptor binding and microvascular density
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325964/
https://www.ncbi.nlm.nih.gov/pubmed/32655346
http://dx.doi.org/10.3389/fnins.2020.00519
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