HPA axis dysregulation in mice overexpressing corticotropin releasing hormone

Groenink, Lucianne; Dirks, Anneloes; Verdouw, P. Monika; Schipholt, Marlies lutje; Veening, Jan G.; Gugten, Jan van der; Olivier, Berend

doi:10.1016/s0006-3223(02)01334-3

Cited by 116 publications

(83 citation statements)

References 48 publications

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“…Silencing of CRH gene exclusively in the central amygdala in adult mice attenuated stress-induced anxiety-like behaviors and increased basal CORT levels (Regev et al 2012). Central CRH delivery elevates heart rate and blood pressure while decreases heart rate variability (Arlt et al 2003), similar to that seen under stress or in CRH overexpressing mice (Dirks et al 2002). LC also plays a pivotal role in translation of stress challenges to bodily cardiovascular responses.…”

Section: Life Without Crh -From Paraventricular Lesions To Crh-ko Micmentioning

confidence: 89%

“…These animals do not have Cushing-like phenotype, however display chronic stress-like neuroendocrine and autonomic changes, HPA axis abnormalities and their behavior is reminiscent to that of seen in depression (Groenink et al 2002).…”

Section: Life With Excess Crh-41mentioning

confidence: 98%

“…Further on, CRH overexpressing mice were generated in which CRH gene is under the control of Thy-1 promoter and the transgene expression is limited to neural tissues (Dirks et al 2002).…”

Section: Life With Excess Crh-41mentioning

confidence: 99%

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CRH: The link between hormonal-, metabolic- and behavioral responses to stress

Kovács

2013

Journal of Chemical Neuroanatomy

108

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Two major and mutually interconnected brain systems are recruited during stress reaction. One is the hypothalamic paraventricular nucleus (PVH) and the second is the extended amygdala. PVH governs the neuroendocrine stress response while CeA regulates most of the autonomic and behavioral stress reactions. The common neurohormonal mediator of these responses is the corticotropin-releasing hormone, CRH, which is expressed in both centers. CRH belongs to a larger family of neuropeptides that also includes urocortins 1, 2, and 3 all have different affinity towards the two types of CRHR receptors and have been implicated in regulation of stress and HPA axis activity. One functionally relevant aspect of CRH systems is their differential regulation by glucocorticoids. While corticosterone inhibits CRH transcription in the PVH, stress-induced glucocorticoids stimulate CRH expression in the extended amygdala. This review summarizes past and recent findings related to CRH gene regulation and its involvement in the neuroendocrine, autonomic and behavioral stress reaction.Key words: Corticotropin-releasing hormone, paraventricular nucleus, central amygdala, bed nucleus of stria terminalis, corticosterone, cAMP-response element.

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Section: Life Without Crh -From Paraventricular Lesions To Crh-ko Micmentioning

confidence: 89%

Section: Life With Excess Crh-41mentioning

confidence: 98%

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CRH: The link between hormonal-, metabolic- and behavioral responses to stress

Kovács

2013

Journal of Chemical Neuroanatomy

108

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“…To assess whether there is an altered GR-mediated negative feedback we assessed the effects of the synthetic glucocorticoid dexamethasone which at low doses, such as that used here, acts as a GR agonist (Meijer et al, 1998;Cole et al, 2000;Groenink et al, 2002). Mice lacking mGluR7 show a clear hypersensitivity to dexamethasone at the lower dose tested (0.03 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

“…The dexamethasone suppression test was carried out essentially as described by Groenink et al (2002). Male mGluR7 À/À and littermate mGluR7 + / + mice were injected subcutaneously (SC) with saline, 0.03 or 0.1 mg/kg dex-amethasone-21-phosphate disodium salt (Fluka, Buchs, Switzerland).…”

Section: Blood Sample Collection Following Dexamethasone Suppression mentioning

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

125

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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.

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Major Depression and Animals Models

Wong¹

2005

Biology of Depression

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HPA axis dysregulation in mice overexpressing corticotropin releasing hormone

Cited by 116 publications

References 48 publications

CRH: The link between hormonal-, metabolic- and behavioral responses to stress

CRH: The link between hormonal-, metabolic- and behavioral responses to stress

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

Major Depression and Animals Models

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