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2011 | 71 | S |
Tytuł artykułu

The influence of conditional inactivation of GR in noradrenergic system on stress related behavior in mice

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Depression is a mental disease affecting complex cognitive and emotional functions. Stress induced hyperactivity of hypothalamic-pituitary-adrenal system (HPA) is believed to be one of the major contributors to its pathology. The activity of HPA is controlled by glucocorticoid receptors (GR) which function may be impaired in depression, resulting in reduced GR-mediated negative feedback on the HPA-axis. Most of the compounds which modulate GR action also influence noradrenergic system by increasing noradreneline levels. The aim of this study was to investigate if conditional inactivation of GR in noradrenergic neurons of mice affects the animal behavior in stressful conditions. Selective ablation of GR in noradrenergic system was achieved using the Cre/loxP approach by crossing transgenic mice hosting the Cre recombinase under the dopamine beta-hydroxylase (DBH) promoter with animals harboring the floxed GR gene. Resulting GRDBHCre mutant mice were born at expected rates, viable and showed no obvious physical impairment regarding life span, weight gain and locomotor activity. Also plasma cortisol levels did not differ between mutant and control mice. Animals were screened for anxiety and depressive-like behavior in light/ dark box test (LDT) and tail suspension test (TST). Male mutant mice did not unveil any differences from their control littermates in basal state nor after acute restraint stress (2 hrs). However, both tests performed after chronic restraint stress (14 days, 2 hrs/day) revealed that GRDBHCre mice were resistant to this type of experimental procedure showing similar anxiety status and immobility time as non-stressed controls. Our mutant mice may represent an interesting tool to study the role of stress in depression in context of noradrenergic system which is important target for antidepressant therapy. This study was supported by grant POIG.01.01.02-12-004/09 (DeMeTer) financed by European Regional Development Fund.
Słowa kluczowe
Wydawca
-
Rocznik
Tom
71
Numer
S
Opis fizyczny
p.78
Twórcy
autor
  • Department of Brain Biochemistry, Institute of Pharmacology PNS, Krakow, Poland
autor
  • Department of Brain Biochemistry, Institute of Pharmacology PNS, Krakow, Poland
  • Department of Brain Biochemistry, Institute of Pharmacology PNS, Krakow, Poland
autor
  • German Cancer Research Center, Department Molecular Biology of the Cell I, Heidelberg, Germany
autor
  • German Cancer Research Center, Department Molecular Biology of the Cell I, Heidelberg, Germany
autor
  • Department of Brain Biochemistry, Institute of Pharmacology PNS, Krakow, Poland
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Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-02dd73a1-43c0-4807-baf7-203c105ada29
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