Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients
Year: 2021
Type: article
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.
Source: Translational Psychiatry
Language: English
Subfield: Behavioral Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,380
Funders: National Science Foundation, Mayo Clinic, Leona M. and Harry B. Helmsley Charitable Trust, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences
Awards: G114280915, G1715294275, G1767599178, High-throughput mapping of selectively vulnerable cell types and projections in aging and Alzheimer's Disease, G2098712733, G219020131, G2252007175, San Diego Nathan Shock Center, G2581418637, G2647008266, G3166661418, G3266624898, G4088506818, Inherited Variations In Drug Metabolizing Enzymes, G5439019025, G5520316217, G680976502, G9000055537, G9000085250, G9000150557, G9000258299, G9000279958, The Discovery of Human Peptide Encoding Genes
OpenAlex ID: W3215045676