Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Anne-Louise Gannon, Laura O’Hara, J. Ian Mason, Diane Rebourcet, Sarah Smith, Adriana Traveres, Carlos Jose Alcaide-Corral, Hanne Frederiksen, Anne Jørgensen, Laura Milne, Rod T. Mitchell, Lee B. Smith

ABSTRACT

The hypothalamic-pituitary-adrenal (HPA) axis regulates responses to internal and external stressors. Many patients diagnosed with conditions such as depression or anxiety also have hyperactivity of the HPA axis. Hyper-stimulation of the HPA axis results in sustained elevated levels of glucocorticoids which impair neuronal function and can ultimately result in a psychiatric disorder. Studies investigating Glucocorticoid Receptor (GR/NR3C1) in the brain have primarily focused on the forebrain, however in recent years, the hindbrain has become a region of interest for research into the development of anxiety and depression, though the role of GR signalling in the hindbrain remains poorly characterised. To determine the role of glucocorticoid signalling in the hindbrain we have developed a novel mouse model that specifically ablates hindbrain GR to ascertain its role in behaviour, HPA-axis regulation and adrenal structure. Our study highlights that ablation of GR in the hindbrain results in excessive barbering, obsessive compulsive digging and lack of cage exploration. These mice also develop kyphosis, elevated circulating corticosterone and severe adrenal cortex disruption. Together, this data demonstrates a role for hindbrain GR signalling in regulating stress-related behaviour and identifies a novel mouse model to allow further investigation into the pathways impacting stress and anxiety. More... »

PAGES

3250

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-39867-y

DOI

http://dx.doi.org/10.1038/s41598-019-39867-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112475546

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30824750


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