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Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity?

Corticotropin releasing hormone (CRH) produced by the hypothalamus initiates the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the body’s stress response. CRH levels typically are undetectable in human plasma, but during pregnancy the primate placenta synthesizes and releases large amou...

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Autores principales: Curran, Megan M., Sandman, Curt A., Poggi Davis, Elysia, Glynn, Laura M., Baram, Tallie Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489219/
https://www.ncbi.nlm.nih.gov/pubmed/28658297
http://dx.doi.org/10.1371/journal.pone.0180311
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author Curran, Megan M.
Sandman, Curt A.
Poggi Davis, Elysia
Glynn, Laura M.
Baram, Tallie Z.
author_facet Curran, Megan M.
Sandman, Curt A.
Poggi Davis, Elysia
Glynn, Laura M.
Baram, Tallie Z.
author_sort Curran, Megan M.
collection PubMed
description Corticotropin releasing hormone (CRH) produced by the hypothalamus initiates the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the body’s stress response. CRH levels typically are undetectable in human plasma, but during pregnancy the primate placenta synthesizes and releases large amounts of CRH into both maternal and fetal circulations. Notably, placental CRH synthesis increases in response to maternal stress signals. There is evidence that human fetal exposure to high concentrations of placental CRH is associated with behavioral consequences during infancy and into childhood, however the direct effects on of the peptide on the human brain are unknown. In this study, we used a rodent model to test the plausibility that CRH has direct effects on the developing cortex. Because chronic exposure to CRH reduces dendritic branching in hippocampal neurons, we tested the hypothesis that exposure to CRH would provoke impoverishment of dendritic trees in cortical neurons. This might be reflected in humans as cortical thinning. We grew developing cortical neurons in primary cultures in the presence of graded concentrations of CRH. We then employed Sholl analyses to measure dendritic branching and total dendritic length of treated cells. A seven-day exposure to increasing levels of CRH led to a significant, dose-dependent impoverishment of the branching of pyramidal-like cortical neurons. These results are consistent with the hypothesis that, rather than merely being a marker of prenatal stress, CRH directly decreases dendritic branching. Because dendrites comprise a large portion of cortical volume these findings might underlie reduced cortical thickness and could contribute to the behavioral consequences observed in children exposed to high levels of CRH in utero.
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spelling pubmed-54892192017-07-11 Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity? Curran, Megan M. Sandman, Curt A. Poggi Davis, Elysia Glynn, Laura M. Baram, Tallie Z. PLoS One Research Article Corticotropin releasing hormone (CRH) produced by the hypothalamus initiates the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the body’s stress response. CRH levels typically are undetectable in human plasma, but during pregnancy the primate placenta synthesizes and releases large amounts of CRH into both maternal and fetal circulations. Notably, placental CRH synthesis increases in response to maternal stress signals. There is evidence that human fetal exposure to high concentrations of placental CRH is associated with behavioral consequences during infancy and into childhood, however the direct effects on of the peptide on the human brain are unknown. In this study, we used a rodent model to test the plausibility that CRH has direct effects on the developing cortex. Because chronic exposure to CRH reduces dendritic branching in hippocampal neurons, we tested the hypothesis that exposure to CRH would provoke impoverishment of dendritic trees in cortical neurons. This might be reflected in humans as cortical thinning. We grew developing cortical neurons in primary cultures in the presence of graded concentrations of CRH. We then employed Sholl analyses to measure dendritic branching and total dendritic length of treated cells. A seven-day exposure to increasing levels of CRH led to a significant, dose-dependent impoverishment of the branching of pyramidal-like cortical neurons. These results are consistent with the hypothesis that, rather than merely being a marker of prenatal stress, CRH directly decreases dendritic branching. Because dendrites comprise a large portion of cortical volume these findings might underlie reduced cortical thickness and could contribute to the behavioral consequences observed in children exposed to high levels of CRH in utero. Public Library of Science 2017-06-28 /pmc/articles/PMC5489219/ /pubmed/28658297 http://dx.doi.org/10.1371/journal.pone.0180311 Text en © 2017 Curran et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Curran, Megan M.
Sandman, Curt A.
Poggi Davis, Elysia
Glynn, Laura M.
Baram, Tallie Z.
Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity?
title Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity?
title_full Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity?
title_fullStr Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity?
title_full_unstemmed Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity?
title_short Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity?
title_sort abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (crh): insights into effects of prenatal adversity?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489219/
https://www.ncbi.nlm.nih.gov/pubmed/28658297
http://dx.doi.org/10.1371/journal.pone.0180311
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