TY - JOUR
T1 - Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients
AU - Heard, Kelly J.
AU - Shokhirev, Maxim N.
AU - Becronis, Caroline
AU - Fredlender, Callie
AU - Zahid, Nadia
AU - Le, Amy T.
AU - Ji, Yuan
AU - Skime, Michelle
AU - Nelson, Timothy
AU - Hall-Flavin, Daniel
AU - Weinshilboum, Richard
AU - Gage, Fred H.
AU - Vadodaria, Krishna C.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41398-021-01733-9
DO - 10.1038/s41398-021-01733-9
M3 - Article
C2 - 34848679
AN - SCOPUS:85120160141
SN - 2158-3188
VL - 11
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 608
ER -