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

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Harvard

Gannon, A-L, O'Hara, L, Mason, JI, Rebourcet, D, Smith, S, Traveres, A, Alcaide-Corral, CJ, Frederiksen, H, Jørgensen, A, Milne, L, Mitchell, RT & Smith, LB 2019, 'Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders' Scientific Reports, bind 9, nr. 1, s. 3250. https://doi.org/10.1038/s41598-019-39867-y

APA

Gannon, A-L., O'Hara, L., Mason, J. I., Rebourcet, D., Smith, S., Traveres, A., ... Smith, L. B. (2019). Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders. Scientific Reports, 9(1), 3250. https://doi.org/10.1038/s41598-019-39867-y

CBE

MLA

Vancouver

Author

Gannon, Anne-Louise ; O'Hara, Laura ; Mason, J Ian ; Rebourcet, Diane ; Smith, Sarah ; Traveres, Adriana ; Alcaide-Corral, Carlos Jose ; Frederiksen, Hanne ; Jørgensen, Anne ; Milne, Laura ; Mitchell, Rod T ; Smith, Lee B. / Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders. I: Scientific Reports. 2019 ; Bind 9, Nr. 1. s. 3250.

Bibtex

@article{4cb3418927fb445cbd509c75964c5adb,
title = "Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders",
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.",
author = "Anne-Louise Gannon and Laura O'Hara and Mason, {J Ian} and Diane Rebourcet and Sarah Smith and Adriana Traveres and Alcaide-Corral, {Carlos Jose} and Hanne Frederiksen and Anne J{\o}rgensen and Laura Milne and Mitchell, {Rod T} and Smith, {Lee B}",
year = "2019",
month = "3",
day = "1",
doi = "10.1038/s41598-019-39867-y",
language = "English",
volume = "9",
pages = "3250",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders

AU - Gannon, Anne-Louise

AU - O'Hara, Laura

AU - Mason, J Ian

AU - Rebourcet, Diane

AU - Smith, Sarah

AU - Traveres, Adriana

AU - Alcaide-Corral, Carlos Jose

AU - Frederiksen, Hanne

AU - Jørgensen, Anne

AU - Milne, Laura

AU - Mitchell, Rod T

AU - Smith, Lee B

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-019-39867-y

DO - 10.1038/s41598-019-39867-y

M3 - Journal article

VL - 9

SP - 3250

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -

ID: 56741688