Expression and glucocorticoid-dependent regulation of the stress-inducible protein DRR1 in the mouse adult brain

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  • Mercè Masana, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. mmasana@ub.edu.
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  • Sören Westerholz, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
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  • Anja Kretzschmar, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
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  • Giulia Treccani
  • Claudia Liebl, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
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  • Sara Santarelli, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
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  • Carine Dournes, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
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  • Maurizio Popoli, Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Università di Milano, Milan, Italy.
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  • Mathias V Schmidt, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
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  • Theo Rein, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
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  • Marianne B Müller, Deutsches Resilienz-Zentrum, Mainz, Germany.

Identifying molecular targets that are able to buffer the consequences of stress and therefore restore brain homeostasis is essential to develop treatments for stress-related disorders. Down-regulated in renal cell carcinoma 1 (DRR1) is a unique stress-induced protein in the brain and has been recently proposed to modulate stress resilience. Interestingly, DRR1 shows a prominent expression in the limbic system of the adult mouse. Here, we analyzed the neuroanatomical and cellular expression patterns of DRR1 in the adult mouse brain using in situ hybridization, immunofluorescence and Western blot. Abundant expression of DRR1 mRNA and protein was confirmed in the adult mouse brain with pronounced differences between distinct brain regions. The strongest DRR1 signal was detected in the neocortex, the CA3 region of the hippocampus, the lateral septum and the cerebellum. DRR1 was also present in circumventricular organs and its connecting regions. Additionally, DRR1 was present in non-neuronal tissues like the choroid plexus and ependyma. Within cells, DRR1 protein was distributed in a punctate pattern in several subcellular compartments including cytosol, nucleus as well as some pre- and postsynaptic specializations. Glucocorticoid receptor activation (dexamethasone 10 mg/kg s.c.) induced DRR1 expression throughout the brain, with particularly strong induction in white matter and fiber tracts and in membrane-rich structures. This specific expression pattern and stress modulation of DRR1 point to a role of DRR1 in regulating how cells sense and integrate signals from the environment and thus in restoring brain homeostasis after stressful challenges.

Original languageEnglish
JournalBrain Structure and Function (Print Edition)
Volume223
Issue9
Pages (from-to)4039–4052
ISSN1863-2653
DOIs
Publication statusPublished - Dec 2018

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