Environmental enrichment prevents stress-induced epigenetic changes in the expression of glucocorticoid receptor and corticotrophin releasing hormone in the central nucleus of the amygdala to inhibit visceral hypersensitivity

• Published in: Experimental neurology 2021-11, Vol.345, p.113841-113841, Article 113841
• Main Authors: Orock, A., Louwies, T., Ligon, C.O., Mohammadi, E., Greenwood-Van Meerveld, B.
• Format: Article
• Language: English
• Subjects: Animals; Brain-gut communication; Central Amygdaloid Nucleus - metabolism; colon permeability; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - metabolism; Environment; Epigenesis, Genetic - physiology; Epigenetics; Female; Rats; Rats, Inbred F344; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Somatic sensitivity; Stress; Visceral Pain - genetics; Visceral Pain - metabolism; Visceral Pain - prevention & control; Visceral sensitivity
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2021.113841

Stress is a known trigger for the symptoms of irritable bowel syndrome (IBS), a gastrointestinal (GI) disorder that presents with abnormal bowel habits and abdominal pain due to visceral hypersensitivity. While behavioral therapies have been used to attenuate IBS symptoms, the underlying mechanisms by which these therapies interact with stress-induced pathology remains to be delineated. Here we use a rat model to test the hypothesis that exposure to environmental enrichment (EE) inhibits stress-induced changes within the brain-gut axis to prevent visceral and somatic hypersensitivity and colonic hyperpermeability. Female rats (n = 8/group) were housed in EE one week before and one week during exposure to water avoidance stress (WAS) while controls were housed in standard cages (SH). One day after the final WAS exposure, colonic and somatic sensitivity were assessed by the visceromotor response (VMR) to colorectal distension (CRD) and withdrawal threshold elicited by an electronic von Frey on the hind paw of the rats respectively. All rats were returned to SH for 3 weeks before colonic and somatic sensitivity were reassessed on day 28. The rats were then immediately euthanized and the spinal cord was collected to assess changes in neuronal activation (assessed via ERK phosphorylation) in response to noxious CRD. A separate cohort of animals (n = 8/group) that did not undergo behavioral assessments was euthanized the day after the final WAS exposure and the central nucleus of the amygdala (CeA) was collected to investigate WAS and EE induced epigenetic changes at the glucocorticoid receptor (GR) and corticotrophin releasing hormone (CRH) promoter. The colon from these rats was also collected to assess colonic permeability via changes in transepithelial electrical resistance (TEER) in vitro. Exposure to stress persistently increased VMR to CRD (P