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European Archives of Psychiatry and Clinical Neuroscience
Published in: European Archives of Psychiatry and Clinical Neuroscience 8/2009

Open Access 01-12-2009 | Short Communication

Reduced hippocampal neurogenesis in the GR+/− genetic mouse model of depression

Authors: Golo Kronenberg, Imke Kirste, Dragos Inta, Sabine Chourbaji, Isabella Heuser, Matthias Endres, Peter Gass

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 8/2009

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Abstract

Glucocorticoid receptor (GR) heterozygous mice (GR+/− ) represent a valuable animal model for major depression. GR+/− mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR+/− animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR+/− genotype on neurogenesis in vivo. In a 2 × 2 design, GR+/− mice and GR+/+ littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR+/− genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic marker S100β with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR+/− mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression.
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Metadata
Title
Reduced hippocampal neurogenesis in the GR+/− genetic mouse model of depression
Authors
Golo Kronenberg
Imke Kirste
Dragos Inta
Sabine Chourbaji
Isabella Heuser
Matthias Endres
Peter Gass
Publication date
01-12-2009
Publisher
D. Steinkopff-Verlag
Published in
European Archives of Psychiatry and Clinical Neuroscience / Issue 8/2009
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-009-0036-y

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