Brain and Gut CRF Signaling: Biological Actions and Role in the Gastrointestinal Tract

Abstract

The translational potential of CRF-R1 antagonists in gut diseases will require additional studies directed to novel anti-CRF therapies and the neurobiology of brain-gut interactions under chronic stress.

The effect of a mindfulness-based therapy on different biomarkers among patients with inflammatory bowel disease: a randomised controlled trial

“…Although we found no differences in cortisol between IBD patients in the MBI and the SMT groups at the molecular level, other groups have described relatively high levels of stress and psychological dysfunction among patients with CD or UC 47,51 . Stress increases gastrointestinal (GI) tract permeability and modifies gut microbiota to promote the pathophysiology of IBD through corticotropin-releasing factor (CRF) and urocortin; 47,52-54 these neuromediators then act on G-protein coupled CRF1 and CFR2 receptors in the brain and GI tract 53 . CRF2 receptors are involved in the perturbation of intestinal permeability.…”

“…Chronic early-life stress alters intestinal permeability in rats, which may later sensitise adult rats to visceral hypersensitivity and induce dysbiosis 56 . Stress also inhibits the vagus nerve (VN) and stimulates the sympathetic nervous system via autonomic nervous system-related paraventricular hypothalamic nucleus projection neurons; these are connected to the VN dorsal motor nucleus and sympathetic pre-ganglionic neurons of the spinal cord 53 . Indeed, because the VN exerts an anti-inflammatory effect through its afferent and efferent fibres, stress can be considered a pro-inflammatory process.…”

Brain corticotropin‐releasing factor signaling: Involvement in acute stress‐induced visceral analgesia in male rats

“…Numerous evidence support a role for increased intestinal permeability, activation of mast cells, increase of serotonin release by direct action on cells that express CRF 1 receptors in the hyperalgesic visceral response to peripheral injection of CRF or CRF 1 agonists (for a review, see Ref. ). The differential modulation of visceral pain by CRF injected into the brain or peripherally also implies that ICV CRF acts in the brain independently of pituitary hormones including β‐endorphin that are released into the peripheral circulation by both routes of CRF administration …”

Traumatic stress and the autonomic brain‐gut connection in development: Polyvagal Theory as an integrative framework for psychosocial and gastrointestinal pathology

“…Preclinical studies support the role of corticotrophin releasing factor (CRF) signaling affecting gastric acid secretion, gastric and small intestinal transit, mucosal permeability, and visceral hypersensitivity via ANS effects (Tache, Larauche, Yuan, & Million, ). Centrally injected CRF causes disturbed GI secretomotor function and anxiety‐like behaviors in animals and reversal of this has been documented using CRF antagonists (Martinez & Taché, ; Tache et al, ). In addition, oxytocinergic projections from the paraventricular nucleus (PVN; located in the hypothalamus) to the DVC increase the sensitivity of vagovagal reflex and serve a protective role in maintaining GI functions during restraint stress (Bülbül, Babygirija, Ludwig, & Takahashi, ; Rogers & Hermann, ; ).…”

“…The hypothalamic-pituitary-adrenal axis has a well-characterized role in perturbation of homeostasis and stressinduced GI symptoms as well as gut inflammation (Bonaz, Sinninger, & Pellissier, 2016;Chrousus, 1995;la Fleur, Wick, Idumalla, Grady, & Bhargava, 2005;Mayer, 2011). Preclinical studies support the role of corticotrophin releasing factor (CRF) signaling affecting gastric acid secretion, gastric and small intestinal transit, mucosal permeability, and visceral hypersensitivity via ANS effects (Tache, Larauche, Yuan, & Million, 2018). Centrally injected CRF causes disturbed GI secretomotor function and anxiety-like behaviors in animals and reversal of this has been documented using CRF antagonists (Martinez & Taché, 2006;Tache et al, 2018).…”