Abnormal Dendritic Maturation of Developing Cortical Neurons Exposed to Corticotropin Releasing Hormone (CRH): Insights into Effects of Prenatal Adversity?

Authors

Megan M. Curran, University of California, Irvine
Curt A. Sandman, University of California, Irvine
Elyssia Poggi Davis, University of California, Irvine
Laura M. Glynn, Chapman UniversityFollow
Tallie Z. Baram, University of California, Irvine

Document Type

Article

Publication Date

6-28-2017

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.

Comments

This article was originally published in PLoS ONE, volume 12, issue 6, in 2017. DOI: 10.1371/journal.pone.0180311

Recommended Citation

Curran MM, Sandman CA, Poggi Davis E, Glynn LM, Baram TZ (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

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