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Brain Struct Funct. 2018 Dec;223(9):4039-4052. doi: 10.1007/s00429-018-1737-7. Epub 2018 Aug 18.

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

Author information

1
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany. mmasana@ub.edu.
2
Translational Psychiatry, Department of Psychiatry and Psychotherapy and Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Hanns-Dieter-Hüsch-Weg 19, 55128, Mainz, Germany. mmasana@ub.edu.
3
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. mmasana@ub.edu.
4
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
5
Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Università di Milano, Milan, Italy.
6
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
7
Translational Psychiatry, Department of Psychiatry and Psychotherapy and Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Hanns-Dieter-Hüsch-Weg 19, 55128, Mainz, Germany.
8
Deutsches Resilienz-Zentrum, Mainz, Germany.

Abstract

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.

KEYWORDS:

Brain mRNA expression; Brain protein expression; Fam107A; Glucocorticoids; Stress; Tu3a

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