Neurogastroenterology and motility · 2015
Enteric glial cells are associated with stress-induced colonic hyper-contraction in maternally separated rats.
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Fujikawa Y, Tominaga K, Tanaka F, Tanigawa T, Watanabe T, Fujiwara Y, Arakawa T
Аннотация
BACKGROUND: Enteric glial cells (EGCs) play important roles in enteric integrity and regulation of gastrointestinal function. However, whether EGCs undergo pathophysiological changes in stress-associated gastrointestinal disorders is unknown. We investigated structural and functional alterations in colonic EGCs and their roles in colonic contraction in an irritable bowel syndrome (IBS) model.
METHODS: As a chronic stress, male Wistar rats underwent 3-h maternal separation during postnatal days 2-14. As an acute stress, we used water-immersion stress (4 h) in adulthood (at 8 weeks). We quantitatively and morphologically evaluated enteric neurons and EGCs using whole-mount longitudinal muscle-myenteric plexus preparations. Colonic contraction was analyzed with electrical field stimulation (EFS).
KEY RESULTS: Glial fibrillary acidic protein (GFAP) expression and the number of total, cholinergic, and nitrergic neurons were unchanged in maternally separated rats with acute stress (combined stress: an IBS model) compared with controls. However, the density of GFAP-positive EGC processes that apparently overlapped with the neurons and the extent of bulbous swelling of terminals increased according to the stress intensity: control, acute stress, maternal separation, and combined stress. EFS-induced colonic contractions were significantly greater in the combined stress rats than in controls. Higher dose of fluorocitrate, a selective inhibitor of EGC metabolism, was required to inhibit both EFS-induced contraction and EGCs activation in the combined stress rats than in controls.
CONCLUSIONS & INFERENCES: Colonic EGCs exhibited structural alterations according to the stress intensity. EGCs were associated with stress-induced colonic hyper-contraction in the combined stress rats, which may underlie the pathogenesis of IBS.
METHODS: As a chronic stress, male Wistar rats underwent 3-h maternal separation during postnatal days 2-14. As an acute stress, we used water-immersion stress (4 h) in adulthood (at 8 weeks). We quantitatively and morphologically evaluated enteric neurons and EGCs using whole-mount longitudinal muscle-myenteric plexus preparations. Colonic contraction was analyzed with electrical field stimulation (EFS).
KEY RESULTS: Glial fibrillary acidic protein (GFAP) expression and the number of total, cholinergic, and nitrergic neurons were unchanged in maternally separated rats with acute stress (combined stress: an IBS model) compared with controls. However, the density of GFAP-positive EGC processes that apparently overlapped with the neurons and the extent of bulbous swelling of terminals increased according to the stress intensity: control, acute stress, maternal separation, and combined stress. EFS-induced colonic contractions were significantly greater in the combined stress rats than in controls. Higher dose of fluorocitrate, a selective inhibitor of EGC metabolism, was required to inhibit both EFS-induced contraction and EGCs activation in the combined stress rats than in controls.
CONCLUSIONS & INFERENCES: Colonic EGCs exhibited structural alterations according to the stress intensity. EGCs were associated with stress-induced colonic hyper-contraction in the combined stress rats, which may underlie the pathogenesis of IBS.