Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients

Abstract Major depressive disorder (MDD) is a prevalent psychiatric disorder, and exposure to stress is a robust risk factor for MDD. Clinical data and rodent models have indicated the negative impact of chronic exposure to stress-induced hormones like cortisol on brain volume, memory, and cell meta...

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Autores principales:	Kelly J. Heard, Maxim N. Shokhirev, Caroline Becronis, Callie Fredlender, Nadia Zahid, Amy T. Le, Yuan Ji, Michelle Skime, Timothy Nelson, Daniel Hall-Flavin, Richard Weinshilboum, Fred H. Gage, Krishna C. Vadodaria
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/753b9b999f8c450c8e0472172f86f547
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spelling	oai:doaj.org-article:753b9b999f8c450c8e0472172f86f5472021-12-05T12:07:44ZChronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients10.1038/s41398-021-01733-92158-3188https://doaj.org/article/753b9b999f8c450c8e0472172f86f5472021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01733-9https://doaj.org/toc/2158-3188Abstract Major depressive disorder (MDD) is a prevalent psychiatric disorder, and exposure to stress is a robust risk factor for MDD. Clinical data and rodent models have indicated the negative impact of chronic exposure to stress-induced hormones like cortisol on brain volume, memory, and cell metabolism. However, the cellular and transcriptomic changes that occur in the brain after prolonged exposure to cortisol are less understood. Furthermore, the astrocyte-specific contribution to cortisol-induced neuropathology remains understudied. Here, we have developed an in vitro model of “chronic stress” using human induced pluripotent stem cell (iPSC)-derived astrocytes treated with cortisol for 7 days. Whole transcriptome sequencing reveals differentially expressed genes (DEGs) uniquely regulated in chronic cortisol compared to acute cortisol treatment. Utilizing this paradigm, we examined the stress response transcriptome of astrocytes generated from MDD patient iPSCs. The MDD-specific DEGs are related to GPCR ligand binding, synaptic signaling, and ion homeostasis. Together, these data highlight the unique role astrocytes play in the central nervous system and present interesting genes for future study into the relationship between chronic stress and MDD.Kelly J. HeardMaxim N. ShokhirevCaroline BecronisCallie FredlenderNadia ZahidAmy T. LeYuan JiMichelle SkimeTimothy NelsonDaniel Hall-FlavinRichard WeinshilboumFred H. GageKrishna C. VadodariaNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Kelly J. Heard Maxim N. Shokhirev Caroline Becronis Callie Fredlender Nadia Zahid Amy T. Le Yuan Ji Michelle Skime Timothy Nelson Daniel Hall-Flavin Richard Weinshilboum Fred H. Gage Krishna C. Vadodaria Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients
description	Abstract Major depressive disorder (MDD) is a prevalent psychiatric disorder, and exposure to stress is a robust risk factor for MDD. Clinical data and rodent models have indicated the negative impact of chronic exposure to stress-induced hormones like cortisol on brain volume, memory, and cell metabolism. However, the cellular and transcriptomic changes that occur in the brain after prolonged exposure to cortisol are less understood. Furthermore, the astrocyte-specific contribution to cortisol-induced neuropathology remains understudied. Here, we have developed an in vitro model of “chronic stress” using human induced pluripotent stem cell (iPSC)-derived astrocytes treated with cortisol for 7 days. Whole transcriptome sequencing reveals differentially expressed genes (DEGs) uniquely regulated in chronic cortisol compared to acute cortisol treatment. Utilizing this paradigm, we examined the stress response transcriptome of astrocytes generated from MDD patient iPSCs. The MDD-specific DEGs are related to GPCR ligand binding, synaptic signaling, and ion homeostasis. Together, these data highlight the unique role astrocytes play in the central nervous system and present interesting genes for future study into the relationship between chronic stress and MDD.
format	article
author	Kelly J. Heard Maxim N. Shokhirev Caroline Becronis Callie Fredlender Nadia Zahid Amy T. Le Yuan Ji Michelle Skime Timothy Nelson Daniel Hall-Flavin Richard Weinshilboum Fred H. Gage Krishna C. Vadodaria
author_facet	Kelly J. Heard Maxim N. Shokhirev Caroline Becronis Callie Fredlender Nadia Zahid Amy T. Le Yuan Ji Michelle Skime Timothy Nelson Daniel Hall-Flavin Richard Weinshilboum Fred H. Gage Krishna C. Vadodaria
author_sort	Kelly J. Heard
title	Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients
title_short	Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients
title_full	Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients
title_fullStr	Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients
title_full_unstemmed	Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients
title_sort	chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/753b9b999f8c450c8e0472172f86f547
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Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients

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