- Title
- Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders
- Creator
- Gannon, Anne-Louise; O'Hara, Laura; Mitchell, Rod T.; Smith, Lee B.; Mason, J. Ian; Rebourcet, Diane; Smith, Sarah; Traveres, Adriana; Alcaide-Corral, Carlos Jose; Frederiksen, Hanne; Jorgensen, Anne; Milne, Laura
- Relation
- Medical Research Council Program Grant Award.MR/N002970/1
- Relation
- Scientific Reports Vol. 9, no. 3250
- Publisher Link
- http://dx.doi.org/10.1038/s41598-019-39867-y
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2019
- Description
- 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.
- Subject
- hypothalamic-pituitary-adrenal; depression; anxiety; brain; hyperactivity
- Identifier
- http://hdl.handle.net/1959.13/1455483
- Identifier
- uon:45093
- Identifier
- ISSN:2045-2322
- Rights
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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