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Introduction: The pathophysiology of irritable bowel syndrome (IBS) remains unknown. This study aimed to evaluate colonic motility and serotonin system response to restraint stress (RS) among adolescent rats who underwent neonatal maternal separation (NMS) to clarify the features of pathogenesis in adolescents with IBS. Methods: Male rats were exposed to NMS as chronic stress, and a normally handled (NH) group was used as control. Four groups were created by adding RS as acute stress treatment to the NMS and NH groups. To realize the RS treatment, the subjects were restrained for 1 h at the age of 5 weeks, and hourly fecal pellet discharge was determined. After euthanization and proximal colon intestinal tissue collection, 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine receptor 3 (5-HT3R) concentrations, enterochromaffin (EC) cell density, and the expression of mRNA-encoding slc6a4 were examined. Results: The amount of fecal pellet discharge during RS increased significantly in the RS and NMS+RS groups compared with that in the NH and NMS groups, respectively. The 5-HT concentration in the intestinal tissue of rats in the RS and NMS groups increased significantly compared with that of rats in the NH group. EC cell density also increased significantly in the NMS and NMS+RS groups compared with that in the NH and RS groups. However, combined stress did not result in any significant differences in the expression of 5-HT3R and mRNA-encoding slc6a4. Conclusions: The combination of juvenile and acute stress effectively induced increased 5-HT concentration or EC cell density via the 5-HT pathway in the proximal colon of adolescent rats. [ABSTRACT FROM AUTHOR]

Introduction: Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. Methods: Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. Results: The microarray results indicated significantly higher expression levels of cancer-related genes PIM2 and SPI1 in the active group than in the remission and control groups (p < 0.05). Real-time PCR confirmed that PIM2 and SPI1 expression levels were significantly higher, whereas TP53 and APC expression levels were significantly lower, in the active-phase group than in the remission and control groups (p < 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. Conclusions: Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development. [ABSTRACT FROM AUTHOR]