Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior

Maureen P. Boyle, Judson A. Brewer, Michiyo Funatsu, David F. Wozniak, Joseph Zhuo Tsien, Yukitoshi Izumi, Louis J. Muglia

Research output: Contribution to journalArticle

275 Citations (Scopus)

Abstract

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of major depressive disorder. A number of studies have shown that this dysregulation is correlated with impaired forebrain glucocorticoid receptor (GR) function. To determine whether a primary, acquired deficit in forebrain GR signaling is an etiologic factor in the pathogenesis of depression, we generated a line of mice with time-dependent, forebrain-specific disruption of GR (FBGRKO). These mice develop a number of both physiological and behavioral abnormalities that mimic major depressive disorder in humans, including hyperactivity of the HPA axis, impaired negative feedback regulation of the HPA axis and, increased depression-like behavior. Importantly, a number of these abnormalities are normalized by chronic treatment with the tricyclic antidepressant, imipramine. Our findings suggest that imipramine's proposed activities on forebrain GR function are not essential for its antidepressant effects, and that alteration in GR expression may play a causative role in disease onset of major depressive disorder.

Original languageEnglish (US)
Pages (from-to)473-478
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number2
DOIs
StatePublished - Jan 11 2005
Externally publishedYes

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Glucocorticoid Receptors
Prosencephalon
Depression
Major Depressive Disorder
Imipramine
Tricyclic Antidepressive Agents
Antidepressive Agents

Keywords

  • Knockout mice

ASJC Scopus subject areas

  • General

Cite this

Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. / Boyle, Maureen P.; Brewer, Judson A.; Funatsu, Michiyo; Wozniak, David F.; Tsien, Joseph Zhuo; Izumi, Yukitoshi; Muglia, Louis J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 2, 11.01.2005, p. 473-478.

Research output: Contribution to journalArticle

Boyle, Maureen P. ; Brewer, Judson A. ; Funatsu, Michiyo ; Wozniak, David F. ; Tsien, Joseph Zhuo ; Izumi, Yukitoshi ; Muglia, Louis J. / Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 2. pp. 473-478.
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