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2009 | 69 | 3 |
Tytuł artykułu

Mice with altered glucocorticoid receptor expression as a model for depression

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Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Impaired glucocorticoid receptor (GR) signaling is a postulated mechanism for the pathogenesis of major depression. Since in vivo expression and functional studies of GR are not feasible in humans, we have generated mouse strains that over- or underexpress GR: (1) GR heterozygous mice (GR+/-) with a 50% GR gene dose reduction; and (2) GR transgenic mice (YGR) with a 100% gene dose elevation. GR+/- mice exhibit normal baseline behaviors, but demonstrate after stress exposure increased helplessness, a behavioral correlate of depression in mice. Similar to depressed patients, GR+/- mice have a disinhibited HPA system and a pathological DEX/CRH test. Thus, they represent a murine depression model with good face and construct validity. YGR mice, in contrast, show reduced helplessness after stress exposure, and an improved HPA system feedback regulation. Therefore they are a model for a stress-resistant strain. These models can be used to study plasticity changes underlying the pathogenesis of depressive disorders. As fi rst potential molecular correlate we identifi ed a downregulation of BDNF in the hippocampus of GR+/- mice. Translational approaches, i.e. how to use these models specifi cally for clinically relevant questions, will be discussed.
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-
Rocznik
Tom
69
Numer
3
Opis fizyczny
p.288
Twórcy
autor
  • Central Institute of Mantal Health, Mannheim, Germany
Bibliografia
Typ dokumentu
Bibliografia
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bwmeta1.element.agro-487a1eb1-e7e8-468d-8400-b00781f710b8
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