Chronic activation and dysregulation of the neuroendocrine stress response have severe physiological and psychological consequences, including the development of metabolic and stress-related psychiatric disorders. We provide the first unbiased, cell type-specific, molecular characterization of all three components of the hypothalamic-pituitary- adrenal axis, under baseline and chronic stress conditions. Among others, we identified a previously unreported subpopulation of Abcb1b+ cells involved in stress adaptation in the adrenal gland. We validated our findings in a mouse stress model, adrenal tissues from patients with Cushing's syndrome, adrenocortical cell lines, and peripheral cortisol and genotyping data from depressed patients. This extensive dataset provides a valuable resource for researchers and clinicians interested in the organism's nervous and endocrine responses to stress and the interplay between these tissues. Our findings raise the possibility that modulating ABCB1 function may be important in the development of treatment strategies for patients suffering from metabolic and stress-related psychiatric disorders.
FörderungenAdelis Foundation U.S. NIH NIH Swiss National Science Foundation Else Kroner-Fresenius Stiftung Lister Institute of Preventive Medicine (Lister Institute Research Prize) Medical Research Council Deutsche Forschungsgemeinschaft (DFG, German Research foundation) Canadian Biomarker Integration Network in Depression (CAN-BIND) Alexander von Humboldt Foundation BMBF Perlman Family Foundation Bruno and Simone Licht Ruhman Family Laboratory for Research in the Neurobiology of Stress I-CORE Program of the Planning and Budgeting Committee Federal Ministry of Education and Research ERANET Program - Chief Scientist Office of the Israeli Ministry of Health Israel Science Foundation FP7 Grant from the European Research Council Chan Zuckerberg Initiative DAF (advised fund of Silicon Valley Community Foundation) Helmholtz Association European Molecular Biology Organization