Bidirectional Crosstalk between Stress-Induced Gastric Ulcer and Depression under Chronic Stress

Abstract

Stress contributes to a variety of diseases and disorders such as depression and peptic ulcer. The present study aimed to investigate the correlation between stress ulcer and depression in pathogenesis and treatment by using chronic stress depression (CSD), chronic psychological stress ulcer (CPSU) and water immersion restrain stress models in rats. Our data showed that the ulcer index of the animals after CSD exposure was significantly higher than that of controls. Depression-like behaviors were observed in rat after CPSU exposure. Fluoxetine hydrochloride significantly reduced the ulcer index of rats exposed to CPSU stress, while ranitidine inhibited depression-like behavior of the animals in CSD group. The ulcer index of rats administered with mifepristone after CPSU stress was markedly reduced compared to CPSU group, although there was no significant difference in the depression-like behavior between mifepristone-treated CSD group and naive controls. We also found that the rats exposed to CPSU or CSD stress displayed a lower level of corticosterone than naive controls, however, the acute stress (AS) group showed an opposite result. Additionally, in order to study the relevance of H2 receptors and depression, we treated the CSD group with cimetidine and famotidine respectively. The data showed that cimetidine inhibited depression-like behavior in CSD rats, and famotidine had no impact on depression. Overall our data suggested that the hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be the key role in triggering depression and stress ulcer. Acid-suppressing drugs and antidepressants could be used for treatment of depression and stress ulcer respectively. The occurrence of depression might be inhibited by blocking the central H2 receptors.

Gastro-protective and Anti-stress Efficacies of Monomethyl Fumarate and a Fumaria indica Extract in Chronically Stressed Rats

“…Stressors activate the par ventricular nucleus, giving rise to the release of corticotropin-releasing hormone (CRH), and CRH acts on the pituitary and stimulate the secretion of ACTH, which promotes glucocorticoids release from the adrenal cortex (Herman and Cullinan 1997). Glucocorticoids can not only interfere with tissue Table 3 Effect of methanolic extract of Fumaria indica (MFI), monomethyl fumarate (MMF), and Withania somnifera root extract (WS) on weight of glandular portion of stomach and mucosal parameters in chronic foot-shock stress rats repair, elevate levels of gastric acids and pepsin, but also reduce the secretion of gastric mucus, and eventually impair gastric mucosal barrier resulting in peptic ulcer (Zhang et al 2012). Foot shocked animals are known to activate stress-responsive systems in both brain and peripheral organs, including increased HPA-axis activity Swanson 1981, 1982;Rivest and Rivier 1991) as well as increase in pro-inflammatory cytokine levels both in blood (Morrow et al 1993) and brain (Deak et al 2003(Deak et al , 2005Blandino et al 2006Blandino et al , 2009Arakawa et al 2011).…”

Taurine zinc solid dispersions protect against cold-restraint stress-induced gastric ulceration by upregulating HSP70 and exerting an anxiolytic effect

“…High levels of glucocorticoids may induce or aggravate peptic ulcers, as systemic glucocorticoid treatment is clinically associated with an increased risk of peptic ulcer bleeding (Olsen et al, 2010), and administration of glucocorticoids to experimental animals can result in acute gastric erosion (Filaretova, 2011). Gastric bleeding in rats exposed to acute water immersion and restraint has been attributed to decreased gastric pH and elevated ACTH levels (Zhang et al, 2012). Previous research reported that zinc-deficient rats had higher CORT concentrations after exposure to water-immersion and forced swimming stress, suggesting that zinc supplementation might attenuate cold restraint-induced psychological stress (Watanabe et al, 2010).…”

“…Stress ulcers are one of the most common stress-related disorders that affect the digestive system (Zhang et al, 2012). Severe physical stress is closely associated with gastric ulceration, even in Helicobacter pylori-negative patients (Moriya et al, 2011).…”

Role of Stress, Depression, and Aging in Cognitive Decline and Alzheimer’s Disease

“…Further, chronic stress recapitulates many behavioral characteristics of depression that respond to antidepressants (Willner 2005). Hence, the pathophysiology of depression is intimately intertwined with stress (Zhang et al 2012), while the latter also has an effect on the mechanisms of neuroplasticity (Shors et al 1989;McEwen 1999McEwen , 2002.…”