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Cited by 46Stress Responses and CortisolAdrenal Hormones and DisordersNeuroendocrine regulation and behavior

Effects of genetically altered brain glucocorticoid receptor action on behavior and adrenal axis regulation in mice

Howell, Maureen P., Muglia, Louis J.·2006·Frontiers in Neuroendocrinology
DOI 10.1016/j.yfrne.2006.05.001
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Abstract

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with vulnerability to a number of psychiatric diseases including major depression, bipolar disorder, anxiety disorders, and schizophrenia. The HPA axis is activated in response to stress and in a characteristic circadian rhythm, resulting in the release of glucocorticoid hormones from the adrenal cortex. These hormones act on peripheral target tissues to restore homeostasis to the organism and engage glucocorticoid receptors (GR) in the CNS to control the intensity and duration of the stress response. Alterations in this glucocorticoid sensing system may underlie the HPA axis changes associated with psychiatric disorders. Recently, a number of lines of mice with genetically altered GR signaling in the CNS have been generated to address this hypothesis. Here, we summarize findings from new genetic models that indicate a critical role for GR signaling in the CNS in normal regulation of the HPA axis and behavioral/emotional stability.

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Crossref · 10.1016/j.yfrne.2006.05.001

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  • Chronic exposure to glucocorticoids results in adverse side effects such as osteoporosis, diabetes, hypertension, dyslipidemia, and neurodegeneration.

    “As a matter of fact, chronic exposure to GCs results in various adverse side effects such as osteoporosis, diabetes, hypertension, dyslipidemia, and even neurodegeneration (5, 22).”

    From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [5]

  • Upon stress, the intensity and duration of the HPA response depend on the specific nature of the stressor and on the circadian or ultradian phase at which stress occurs.

    “Upon stress, the intensity and duration of the HPA response both depend on the specific nature of the encountered stressor (5, 11, 12). The precise circadian or ultraradian phase at which stress occurs also profoundly influences the systemic release of GCs, since higher levels are secreted when the challenge coincides with rising pulses (13).”

    From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [5]

  • Broad disruption of the GR allele in the CNS and its targeted deletion in the forebrain or PVN resulted in disinhibition of the HPA axis.

    “Finally, the broad disruption of the GR allele in the CNS [GRNesCre (5)] and its targeted deletion in the forebrain [forebrain-specific GR knock-out; FBGRKO mice] (119), or the PVN all resulted in the disinhibition of the HPA axis (120).”

    From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [5]

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Authors
Howell, M. P., & Muglia, L. J.
Affiliations
  • Allen Institute for Brain Science (US)
  • Washington University in St. Louis (US)
Corresponding author
Muglia, Louis J.
ORCID
Muglia, Louis J.
Venue
Frontiers in Neuroendocrinology
Publisher
Elsevier BV
Published
2006-09
Volume
27
Issue
3
Pages
275-284
ISSN
0091-3022 (ISSN-L)
DOI
10.1016/j.yfrne.2006.05.001
OpenAlex
W2044740725
Cited by
46
References
88
Citations by year
2024: 1 · 2022: 2 · 2021: 2 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 2
FWCI
0.71
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Frontiers in Neuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
glucocorticoid receptor, hypothalamic-pituitary-adrenal axis, stress response, mental illness, depression, anxiety disorders, schizophrenia, bipolar disorder, genetic mouse models, emotional stability, circadian rhythm, adrenal cortex
MeSH terms
Animals, Mental Disorders, Central Nervous System, Disease Models, Animal, Hydrocortisone, Hypothalamo-Hypophyseal System, Mice, Neurologic Mutants, Mice, Transgenic, Models, Genetic, Pituitary-Adrenal System, Receptors, Glucocorticoid, Mice, Knockout, Mice

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