Table 1.
Effect of stress on the Gastrointestinal tract and brain in animal models.
| Stress models | Stomach | Small intestine | Colon | Central nervous system |
|---|---|---|---|---|
| Prenatal stress | Hypersensitivity (66) Dysbiosis (67) Decreased innervation & increase colonic secretory response to adrenaline (68) |
Overactivation of the HPA axis in adulthood with female predominance Epigenetic changes BDNF (SC-female predominance) (67) |
||
| Maternal separation | Susceptibility to erosion (83) Delayed gastric emptying (84) |
Hyperpermeability during separation At weaning, fecal dysbiosis (74) & hyperpermeability (75) Adult hyperpermeability, mostly transcellular pathway associated with abnormal cholinergic regulation (81) Hypersensitivity (76, 78) Immune cells infiltration (MC Eo) (77) Hypersensitivity of neurons from myenteric plexus to IL6 modulation of secretory and motility functions (79) Increased number of enterochromaffin cells & Increased expression SERT (92) |
Decreased activity of glucocorticoid negative feedback (85) increased ACTH response to stressors (86) Increased serotonin concentration in frontal cortex Increased expression 5HT1A/1B/2A in parietal cortex & hippocampus Increased activation of 5HT neuron in raphe magnus and spinal cord (60, 89) Increased sympathetic activity and decreased of parasympathetic activity (94) Increased release of glutamate & AMPA/NMDA receptors involved in remodeling of synapses in hippocampus (95, 96) |
|
| Limited bedding | At weaning, fecal dysbiosis (female predominance) & hyperpermeability (69, 74) In adulthood hypersensitivity (male predominance) (102–104) |
Decreased social/exploratory behavior & impaired learning and memory (102, 103). Decreased dendritic branching hippocampus Altered thalamo-cortico-amygdala pathway Increased connectivity in locus coeruleus (females) (102) Acts on neuronal development of dentate gyrus (105) |
||
| Odor shock conditioning | Hyperpermeability and hypersensitivity through estrogen and GC-C/cGMP pathway; female predominance (104) | Increased expression CRF & GR receptors in central nucleus amygdala (109) | ||
| Water Avoidance Stress | Impaired gastric accommodation at D2 via peripheral 5HT2B signaling (119) Increased postprandial gastric contractions at D2 (120) |
Hyperpermeability at D1 (112, 113) Structural changes mucus layer at D4 (115) Dysbiosis at D8 (117, 118) |
Hyperpermeability at D1 (112, 113) Hypersensitivity at D3 (114) Structural changes mucus layer at D4 (115) Dysbiosis at D10 (117, 118) |
Increased glial, neuronal activation in hypothalamus and amygdala & synaptogenesis in the hippocampus (121, 123) |
| Restrain stress | Increased fecal output CRFR1-dependent manner (37) | Neuronal activation over several brain structures and nuclei including the supraoptic nucleus, locus coeruleus, the ventrolateral medulla, the medial division of the central amygdaloid nucleus, nucleus of the solitary tract and even the dorsal nucleus of the vagus nerve, structures involved in food intake and stress response. Neurons also expressing phoexinin and/or nesfatin (127, 128) |
||
| Partial restraint stress | Delayed gastric emptying through sympathetic activation (36, 137) Increased active ghrelin concentration (137, 139, 140) |
Hypersensitivity (134–136) Hyperpermeability through re-organization of the cytoskeleton (134) Changes in mucosal morphology and decrease of glial cells in the submucosa plexus Increased immune cells infiltration (MC Eo) (135) |
Overactivation of the insular cortex related with colonic hypersensitivity (19) | |
| Crowding stress | Hyperpermeability In WKY rat, activated mast cells (146) |
Increased mast cells density (145) In WKY rat activated mast cells, MPO level & transient hyperpermeability, alteration of mitochondrial activity (146) |
Anxiety-like and depression-like symptoms Early transient changes (Day 3) in the nitrergic expression in the PFC, hippocampus, hypothalamus (147) |
|
| Social isolation | Alterations in the IL-18 pathway and MUC2/TFF3 expression (149) | Anxiety-like and depression-like symptoms Reduced BDNF levels & increased reactivity of the HPA axis (148) Changes in the nitrergic expression in the PFC, hippocampus, hypothalamus (147) |
||
| Abdominal surgery | Impaired gastric emptying Low ghrelin concentration (249, 251, 252) |
Impaired motility through the activation of the inhibitory reflex pathway increased cytokines expression (TNFa, IL1α, IL6, IL1β, CCL2) (241) infiltration resident macrophages (245) |
Impaired motility, delayed transit increased cytokines expression in muscular layers (240) (241) Increased permeability non-related to TLR2/4 (244) |
Activation of nuclei (supraoptic nucleus, locus coeruleus, paraventricular nucleus of the hypothalamus & rostral raphe pallidus) expressing nucleobindin2/nefastin complex involved in the decrease of food intake and GI transit (253) |
5HT, serotonin; 5HT1A/1B/2A/2B, serotonin receptor type 1A, 1B, 2A, 2B; ACTH, adreno cortico trophic hormone; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; BDNF, brain-derived neurotrophic factor; CCL2, chemokine ligand 2; CRH, corticotropin-releasing hormone; CRHR1 corticotropin-releasing hormone receptor type 1; D1/2/3/4/8/10, day 1/2/3/4/8/10; Eo, eosinophils; GC-C/cGMP, guanylate cyclase C/cyclic guanylin monophosphate; GI, Gastrointestinal; GR, Glucocorticoid receptor; HPA, hypothalamus-pituitary-adrenal; IL, interleukin; MC, mast cell; MPO, myeloperoxidase activity; MUC2, Mucin 2; NMDA, N-methyl-D-aspartate; PFC, prefrontal cortex; SC, spinal cord; SERT, serotonin transporter; TFF3, rail fold factor 3; WKY, wistar kyoto.