The Effects of Serotonin on Glucocorticoid Receptor Binding in Rat Raphe Nuclei and Hippocampal Cells in Culture

Héry, Micheline; Sémont, Alexandra; Fache, Marie‐Pierre; Faudon, M.; Héry, F.

doi:10.1046/j.1471-4159.2000.0740406.x

Cited by 45 publications

(27 citation statements)

References 54 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Antidepressants have been reported to increase GR mRNA expression (Carvalho and Pariante, 2008;Funato et al, 2006;Heiske et al, 2003;Vedder et al, 1999), GR protein expression (Carvalho and Pariante, 2008;Hery et al, 2000;Lai et al, 2003;Pepin et al, 1992) and GR function as measured using the translocation of the receptor to the nucleus (Carvalho and Pariante, 2008;Funato et al, 2006;Heiske et al, 2003;Pariante et al, 1997) or dexamethasoneinduced GR-mediated gene transcription (Pariante et al, 2003;Pariante et al, 2001a;Pariante et al, 1997;Pepin et al, 1992). This pattern is opposite to the changes observed here, with less genes significantly regulated by dexamethasone in cases vs controls (1151 vs 2670) and lower fold changes in cases (see Table 2).…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Menke

Arloth

Pütz

et al. 2012

Neuropsychopharmacol

146

126

View full text Add to dashboard Cite

Although gene expression profiles in peripheral blood in major depression are not likely to identify genes directly involved in the pathomechanism of affective disorders, they may serve as biomarkers for this disorder. As previous studies using baseline gene expression profiles have provided mixed results, our approach was to use an in vivo dexamethasone challenge test and to compare glucocorticoid receptor (GR)-mediated changes in gene expression between depressed patients and healthy controls. Whole genome gene expression data (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) from two independent cohorts were analyzed to identify gene expression pattern that would predict case and control status using a training (N ¼ 18 cases/18 controls) and a test cohort (N ¼ 11/13). Dexamethasone led to reproducible regulation of 2670 genes in controls and 1151 transcripts in cases. Several genes, including FKBP5 and DUSP1, previously associated with the pathophysiology of major depression, were found to be reliable markers of GR-activation. Using random forest analyses for classification, GR-stimulated gene expression outperformed baseline gene expression as a classifier for case and control status with a correct classification of 79.1 vs 41.6% in the test cohort. GR-stimulated gene expression performed best in dexamethasone non-suppressor patients (88.7% correctly classified with 100% sensitivity), but also correctly classified 77.3% of the suppressor patients (76.7% sensitivity), when using a refined set of 19 genes. Our study suggests that in vivo stimulated gene expression in peripheral blood cells could be a promising molecular marker of altered GR-functioning, an important component of the underlying pathology, in patients suffering from depressive episodes.

show abstract

Section: Discussionmentioning

confidence: 99%

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Menke

Arloth

Pütz

et al. 2012

Neuropsychopharmacol

146

126

View full text Add to dashboard Cite

show abstract

“…The HPA-axis activity is controlled by a feedback mechanism triggered mainly through the stimulation of GRs located in the cerebral cortex, the hippocampus, and the hypothalamus (Magarinos et al, 1987;Diorio et al, 1993;Feldman and Weidenfeld, 1999;Mizoguchi et al, 2003), and a reduced GR expression and function has been proposed to contribute to HPA-axis alterations in depression (Holsboer and Barden, 1996;Pariante and Miller, 2001;Webster et al, 2002). Further, it is clear that the expression and function of the 5-HT 1A R is regulated by glucocorticoids and GRs (Chalmers et al, 1994;Laaris et al, 1995;Hery et al, 2000;Ou et al, 2001;Andrews et al, 2004;Froger et al, 2004;De Kloet et al, 2005). Taken together these data suggest that there is a selective dysregulation of the integration of the stress response in mGluR7 À/À mice which is opposite to that seen in some human psychopathological states.…”

Section: Discussionmentioning

confidence: 99%

Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders

Mitsukawa

Mombereau

Lötscher

et al. 2005

Neuropsychopharmacol

124

View full text Add to dashboard Cite

Regulation of neurotransmission via group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) has recently been implicated in the pathophysiology of affective disorders, such as major depression and anxiety. For instance, mice with a targeted deletion of the gene for mGluR7 (mGluR7 À/À ) showed antidepressant and anxiolytic-like effects in a variety of stress-related paradigms, including the forced swim stress and the stress-induced hyperthermia tests. Deletion of mGluR7 reduces also amygdala-and hippocampus-dependent conditioned fear and aversion responses. Since the hypothalamic-pituitary-adrenal (HPA) axis regulates the stress response we investigate whether parameters of the HPA axis at the levels of selected mRNA transcripts and endocrine hormones are altered in mGluR7-deficient mice. Over all, mGluR7 À/À mice showed only moderately lower serum levels of corticosterone and ACTH compared with mGluR7 + / + mice. More strikingly however, we found strong evidence for upregulated glucocorticoid receptor (GR)-dependent feedback suppression of the HPA axis in mice with mGluR7 deficiency: (i) mRNA transcripts of GR were significantly upregulated in the hippocampus of mGluR7 À/À animals, (ii) similar increases were seen with 5-HT 1A receptor transcripts, which are thought to be directly controlled by the transcription factor GR and finally (iii) mGluR7 À/À mice showed elevated sensitivity to dexamethasone-induced suppression of serum corticosterone when compared with mGluR7 + / + animals. These results indicate that mGluR7 deficiency causes dysregulation of HPA axis parameters, which may account, at least in part, for the phenotype of mGluR7 À/À mice in animal models for anxiety and depression. In addition, we present evidence that protein levels of brain-derived neurotrophic factor are also elevated in the hippocampus of mGluR7 À/À mice, which we discuss in the context of the antidepressant-like phenotype found in those animals. We conclude that genetic ablation of mGluR7 in mice interferes at multiple sites in the neuronal circuitry and molecular pathways implicated in affective disorders.

show abstract

“…In line with this hypothesis, GR activation by acute administration of dexamethasone to trigger the negative feedback mechanism markedly suppresses ACTH and cortisol secretion normally induced by corticotropin-releasing hormone in control healthy subjects but not in depressed patients (Carrol et al, 1981). Depression-associated deficit in HPA axis regulation might be related to the decreased serotoninergic neurotransmission evidenced in depressed patients (Arango et al, 2001), because GR expression is actually dependent on the central 5-HT tone (Barden, 1999;Héry et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Neurochemical and Behavioral Alterations in Glucocorticoid Receptor-Impaired Transgenic Mice after Chronic Mild Stress

Froger¹,

Palazzo²,

Boni³

et al. 2004

J. Neurosci.

105

View full text Add to dashboard Cite

Mice (GR-i) bearing a transgene encoding a glucocorticoid receptor (GR)antisense RNA under the control of a neuron-specific neurofilament promoter were used to investigate the effects of a 4 week chronic mild stress (CMS) on the hypothalamo-pituitary-adrenocortical (HPA) axis and the serotoninergic system in a transgenic model of vulnerability to affective disorders. GR-i mice showed a decrease in both GR-specific binding (hippocampus and cerebral cortex) and GR mRNA levels [hippocampus, cerebral cortex, and dorsal raphe nucleus (DRN)] as well as a deficit in HPA axis feedback control (dexamethasone test) compared with paired wild-type (WT) mice. In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the density of cytosolic GR binding sites in the hippocampus, whereas, in the DRN, GR mRNA levels tended to increase. In contrast, in stressed GR-i mice, both GR mRNA levels and the density of GR binding sites were significantly increased in the hippocampus, cerebral cortex, and DRN. Electrophysiological recordings in brainstem slices and [␥-35 S]GTP-S binding measurements to assess 5-HT 1A receptor functioning showed that CMS exposure produced a desensitization of DRN 5-HT 1A autoreceptors in WT, but not in GR-i, mice. In addition, CMS was found to facilitate choice behavior of WT, but not GR-i, mice in a decision-making task derived from an alternation paradigm. These results demonstrate that impaired GR functioning affects normal adaptive responses of the HPA axis and 5-HT system to CMS and alters stress-related consequences on decision-making behaviors.

show abstract

The Effects of Serotonin on Glucocorticoid Receptor Binding in Rat Raphe Nuclei and Hippocampal Cells in Culture

Cited by 45 publications

References 54 publications

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders

Neurochemical and Behavioral Alterations in Glucocorticoid Receptor-Impaired Transgenic Mice after Chronic Mild Stress

Contact Info

Product

Resources

About