QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 29, 2005, 25(26):6243-6250; doi:10.1523/JNEUROSCI.0736-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (38) Citing Articles via Google Scholar Google Scholar Articles by Ridder, S. Articles by Gass, P. Search for Related Content PubMed PubMed Citation Articles by Ridder, S. Articles by Gass, P.

 Previous Article  |  Next Article 

Neurobiology of Disease
Mice with Genetically Altered Glucocorticoid Receptor Expression Show Altered Sensitivity for Stress-Induced Depressive Reactions

Stephanie Ridder,^1,2 * Sabine Chourbaji,^2 * Rainer Hellweg,³ Alexandre Urani,² Christiane Zacher,² Wolfgang Schmid,¹ Mathias Zink,² Heide Hörtnagl,⁴ Herta Flor,² Fritz A. Henn,² Günther Schütz,¹ and Peter Gass²

¹Division of Molecular Biology of the Cell I, German Cancer Research Center, D-69120 Heidelberg, Germany, ²Central Institute of Mental Health Mannheim, University of Heidelberg, D-68159 Mannheim, Germany, and ³Department of Psychiatry, Campus Benjamin Franklin, and ⁴Institute of Pharmacology and Toxicology, Charité University Medicine, D-14050 Berlin, Germany

Altered glucocorticoid receptor (GR) signaling is a postulated mechanism for the pathogenesis of major depression. To mimic the human situation of altered GR function claimed for depression, we generated mouse strains that underexpress or overexpress GR, but maintain the regulatory genetic context controlling the GR gene. To achieve this goal, we used the following: (1) GR-heterozygous mutant mice (GR^+/-) with a 50% GR gene dose reduction, and (2) mice overexpressing GR by a yeast artificial chromosome resulting in a twofold gene dose elevation. GR^+/- mice exhibit normal baseline behaviors but demonstrate increased helplessness after stress exposure, a behavioral correlate of depression in mice. Similar to depressed patients, GR^+/- mice have a disinhibited hypothalamic-pituitary-adrenal (HPA) system and a pathological dexamethasone/corticotropin-releasing hormone test. Thus, they represent a murine depression model with good face and construct validity. Overexpression of GR in mice evokes reduced helplessness after stress exposure, and an enhanced HPA system feedback regulation. Therefore, they may represent a model for a stress-resistant strain. These mouse models can now be used to study biological changes underlying the pathogenesis of depressive disorders. As a first potential molecular correlate for such changes, we identified a downregulation of BDNF protein content in the hippocampus of GR^+/- mice, which is in agreement with the so-called neurotrophin hypothesis of depression.

Key words: depression; stress; glucocorticoid receptor; helplessness; transgenic mice; behavior

---

Received Feb 23, 2005; revised May 24, 2005; accepted May 24, 2005.

This article has been cited by other articles:

				G. Kronenberg, C. Harms, R. W. Sobol, F. Cardozo-Pelaez, H. Linhart, B. Winter, M. Balkaya, K. Gertz, S. B. Gay, D. Cox, et al. Folate Deficiency Induces Neurodegeneration and Brain Dysfunction in Mice Lacking Uracil DNA Glycosylase J. Neurosci., July 9, 2008; 28(28): 7219 - 7230. [Abstract] [Full Text] [PDF]

				R.-J. Liu and G. K. Aghajanian Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: Role of corticosterone-mediated apical dendritic atrophy PNAS, January 8, 2008; 105(1): 359 - 364. [Abstract] [Full Text] [PDF]

				M. Fukui, R. M. Rodriguiz, J. Zhou, S. X. Jiang, L. E. Phillips, M. G. Caron, and W. C. Wetsel Vmat2 Heterozygous Mutant Mice Display a Depressive-Like Phenotype J. Neurosci., September 26, 2007; 27(39): 10520 - 10529. [Abstract] [Full Text] [PDF]

				Q. Wei, E. K. Hebda-Bauer, A. Pletsch, J. Luo, M. T. Hoversten, A. J. Osetek, S. J. Evans, S. J. Watson, A. F. Seasholtz, and H. Akil Overexpressing the Glucocorticoid Receptor in Forebrain Causes an Aging-Like Neuroendocrine Phenotype and Mild Cognitive Dysfunction J. Neurosci., August 15, 2007; 27(33): 8836 - 8844. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help