Publication Date

6-28-2017

Document Type

Article

Organizational Units

College of Arts Humanities and Social Sciences, Psychology

Keywords

Corticotropin releasing hormone (CRH), Placenta, Cortical neurons, Dendritic branching

Abstract

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.

Copyright Date

6-28-2017

Copyright Statement / License for Reuse

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Statement

Copyright is held by the authors. User is responsible for all copyright compliance. This article was originally published as:

Curran, M. M., Sandman, C. A., Davis, E. P., Glynn, L. M., & Baram, T. Z. (2017). Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity? PloS One, 12(6), E0180311. https://doi.org/10.1371/journal.pone.0180311

Rights Holder

Megan M. Curran, Curt A. Sandman, Elysia Poggi Davis, Laura M. Glynn, and Tallie Z. Baram

Provenance

Received from CHORUS

File Format

application/pdf

Language

English (eng)

Extent

11 pgs

File Size

4.3 MB

Publication Title

PLoS ONE

Volume

12

Issue

6

First Page

e0180311

ISSN

1932-6203

PubMed ID

28658297

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