Region-specific roles of the corticotropin-releasing factor–urocortin system in stress

Henckens, Marloes J. A. G.; Deussing, Jan M.; Chen, Alon

doi:10.1038/nrn.2016.94

Cited by 208 publications

(200 citation statements)

References 224 publications

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“…We speculate that the heterogeneous expression of CRF 1 and CRF 2 at both pre- and postsynaptic sites (Gallagher et al, 2008; Liu et al, 2004; Orozco-Cabal et al, 2006), as well as the CRF system’s selective modulation of specific CeA glutamatergic inputs as determined by the distribution of CRF 1 and CRF 2 (Gallagher et al, 2008; Liu et al, 2004), results in a predominant upstream network inhibition of evoked glutamate release that acts on distinct sites on our pool of stimulated presynaptic terminals. Accordingly, the Gallagher group (Gallagher et al, 2008; Liu et al, 2004; Orozco-Cabal et al, 2006) reported that CRF and urocortin I (a CRF-related peptide that has a higher affinity for CRF 2 than CRF 1 ) have opposing effects on CeA glutamate transmission, potentially due to their different binding affinities for each CRF receptor subtype and the presynaptic CRF 1 vs. pre- and postsynaptic CRF 2 distributions of their main targets (but see also (Henckens et al, 2016a; Henckens et al, 2016b)). Thus, similar to how the CRF system’s neuromodulation of CeA glutamate release varies based on its pre- and/or postsynaptic receptor expression, it likely also varies in terms of the origin of glutamatergic afferents and CeA target cell types.…”

Section: Discussionmentioning

confidence: 99%

“…The peptide can be synthesized and stored at specific GABAergic and glutamatergic synapses (Cain et al, 1991; Valentino et al, 2001a; Valentino et al, 2001b), and is usually co-released with classical neurotransmitters (Partridge et al, 2016) in response to neuronal firing to modulate their synaptic effects (Rainnie et al, 1992; Yu and Shinnick-Gallagher, 1998). The CRF system can produce a variety of region-, cell type- and synapse-specific effects depending on the distribution of its signaling elements within local and regional circuits (Henckens et al, 2016a). Both CRF 1 and CRF 2 mRNA expression have been detected in the CeA (Van Pett et al, 2000), and their pre- vs. postsynaptic distribution is critical for the CRF-induced inhibition and facilitation of glutamatergic transmission within this nucleus (Liu et al, 2004; Liu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats

et al. 2017

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Corticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) is hypothesized to drive the development of alcohol dependence, as it regulates ethanol intake and several anxiogenic behaviors linked to withdrawal. Excitatory glutamatergic neurotransmission contributes to alcohol reinforcement, tolerance and dependence. Therefore, in this study we used in vitro slice electrophysiology to investigate the effects of CRF and its receptor subtype (CRF1 and CRF2) antagonists on both evoked and spontaneous action potential-independent glutamatergic transmission in the CeA of naive and ethanol-dependent Sprague-Dawley rats. We found that CRF (25–200 nM) concentration-dependently diminished evoked compound excitatory postsynaptic potentials (EPSPs), but increased miniature excitatory postsynaptic current (mEPSC) frequencies similarly in CeA neurons of both naïve and ethanol-dependent rats, indicating reduced evoked glutamatergic responses and enhanced vesicular glutamate release, respectively. This CRF-induced vesicular glutamate release was prevented by the CRF1/2 antagonist (Astressin B) and the CRF1 antagonist (R121919), but not by the CRF2 antagonist (Astressin 2B). Similarly, CRF’s effects on evoked glutamatergic responses were completely blocked by CRF1 antagonism, but only slightly decreased in the presence of the CRF2 antagonist. Moreover, CRF1 antagonism reveals a tonic facilitation of vesicular glutamate, whereas the CRF2 antagonism revealed a tonic inhibition of vesicular glutamate release. Collectively our data show that CRF primarily acts at presynaptic CRF1 to produce opposite effects on CeA evoked and spontaneous glutamatergic release and that the CRF system modulates CeA glutamatergic synapses throughout the development of alcohol dependence.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats

et al. 2017

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“…Selye's observations translate in modern terms to stress-induced immunosuppression, peptic ulceration and inflammatory bowel disease (IBD) and activation of the two main vertebrate stress response systems: the hypothalamic-pituitary-adrenal axis (HPA) and the sympathomedullary system. Stress research has made huge advances since Selye's publication especially with respect to the fundamental neurobiology and neuroendocrinology of the stress response (McEwen 2007, Joels & Baram 2010, Henckens et al 2016. However, uncertainties, irreproducible results and unresolved controversies remain (Fink 2011).…”

Section: Introductionmentioning

confidence: 99%

Selye’s general adaptation syndrome: stress-induced gastro-duodenal ulceration and inflammatory bowel disease

Fink

2017

Journal of Endocrinology

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Hans Selye in a note to Nature in 1936 initiated the field of stress research by showing that rats exposed to nocuous stimuli responded by way of a 'general adaptation syndrome' (GAS). One of the main features of the GAS was the 'formation of acute erosions in the digestive tract, particularly in the stomach, small intestine and appendix'. This provided experimental evidence for the view based on clinical data that gastroduodenal (peptic) ulcers could be caused by stress. This hypothesis was challenged by Marshall and Warren's Nobel Prize (2005)-winning discovery of a causal association between Helicobacter pylori and peptic ulcers. However, clinical and experimental studies suggest that stress can cause peptic ulceration in the absence of H. pylori. Predictably, the etiological pendulum of gastric and duodenal ulceration has swung from 'all stress' to 'all bacteria' followed by a sober realization that both factors play a role, separately as well as together. This raises the question as to whether stress and H. pylori interact, and if so, how? Stress has also been implicated in inflammatory bowel disease (IBD) and related disorders; however, there is no proof yet that stress is the primary etiological trigger for IBD. Central dopamine mechanisms seem to be involved in the stress induction of peptic ulceration, whereas activation of the sympathetic nervous system and central and peripheral corticotrophin-releasing factor appears to mediate stress-induced IBD.

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“…The increased CRH levels, demethylation of Crh, and the decrease in HDAC2 remained present for at least 2 weeks after the end of social defeat. CRH is thought to exert its overall anxiogenic effects by binding to CRH receptor 1 (CRHR1) (Henckens et al 2016). A recent study showed that 21 days of CUS decreased hypothalamic H3K9 trimethylation in the rat, which was correlated with elevated levels of local CRHR1 expression and avoidance behaviour (Wan et al 2014).…”

Section: Corticotropin-releasing Hormone Signallingmentioning

confidence: 99%

Epigenetic programming of the neuroendocrine stress response by adult life stress

Dirven

Homberg

Kozicz

et al. 2017

Journal of Molecular Endocrinology

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The hypothalamic-pituitary-adrenal (HPA) axis is critically involved in the neuroendocrine regulation of stress adaptation, and the restoration of homeostasis following stress exposure. Dysregulation of this axis is associated with stress-related pathologies like major depressive disorder, post-traumatic stress disorder, panic disorder and chronic anxiety. It has long been understood that stress during early life can have a significant lasting influence on the development of the neuroendocrine system and its neural regulators, partially by modifying epigenetic regulation of gene expression, with implications for health and well-being in later life. Evidence is accumulating that epigenetic plasticity also extends to adulthood, proposing it as a mechanism by which psychological trauma later in life can long-lastingly affect HPA axis function, brain plasticity, neuronal function and behavioural adaptation to neuropsychological stress. Further corroborating this claim is the phenomenon that these epigenetic changes correlate with the behavioural consequences of trauma exposure. Thereby, epigenetic modifications provide a putative molecular mechanism by which the behavioural phenotype and transcriptional/translational potential of genes involved in HPA axis regulation can change drastically in response to environmental challenges, and appear an important target for treatment of stress-related disorders. However, improved insight is required to increase their therapeutic (drug) potential. Here, we provide an overview of the growing body of literature describing the epigenetic modulation of the (primarily neuroendocrine) stress response as a consequence of adult life stress and interpret the implications for, and the challenges involved in applying this knowledge to, the identification and treatment of stress-related psychiatric disorders.

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Region-specific roles of the corticotropin-releasing factor–urocortin system in stress

Cited by 208 publications

References 224 publications

CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats

CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats

Selye’s general adaptation syndrome: stress-induced gastro-duodenal ulceration and inflammatory bowel disease

Epigenetic programming of the neuroendocrine stress response by adult life stress

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