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11.
h. nguyen h. wang † t. le w. ho k. a. sharkey & m. g. swain 《Neurogastroenterology and motility》2008,20(3):228-235
Abstract The serotonin neurotransmitter system, including the 5-HT3 receptor, has been implicated in the genesis of fatigue in patients with liver disease. Therefore, we examined the possible role of 5-HT3 receptors in cholestasis-associated fatigue. Rats were either bile duct resected (BDR) or sham resected and studied 10 days postsurgery. A significant decrease in hypothalamic 5-HT3 receptor expression was detected by immunohistochemistry and Western blot in BDR vs sham rats, coupled with increased hypothalamic serotonin turnover identified by an elevated 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT ratio in BDR vs sham rats. To examine fatigue-like behaviour, an activity meter was used. BDR rats exhibited significantly lower locomotor activity than did sham animals. Subcutaneous injection of the 5-HT3 receptor antagonist tropisetron (0.1 mg kg−1 ) resulted in significantly increased locomotor activity in BDR rats compared to the activity in saline-treated controls, but was without effect in sham rats. However, a 10-fold higher dose of tropisetron significantly increased locomotor activity in both BDR and sham rats compared to saline-injected controls. These findings indicate that cholestasis in the rat is associated with increased hypothalamic serotonin turnover, decreased hypothalamic 5-HT3 receptor expression, and enhanced sensitivity to locomotor activation induced by 5-HT3 receptor antagonism, thereby implicating the 5-HT3 receptor system in cholestasis associated fatigue. 相似文献
12.
s. s. natah † a. mouihate † q. j. pittman † & k. a. sharkey † 《Neurogastroenterology and motility》2005,17(3):433-446
Abstract Well-documented central nervous system changes during colitis suggest possible alterations of blood–brain barrier (BBB) permeability, yet the integrity of the BBB has not been fully evaluated in experimental colitis. Our aim was to investigate whether trinitrobenzene sulphonic acid (TNBS) colitis was associated with an increase in the permeability of the BBB. Sprague–Dawley rats were given an intracolonic injection of saline or TNBS and studied 1, 2, 3, 7 and 21 days after treatment. The extravasation of endogenous immunoglobulin G, a large molecule, was not altered at any time after TNBS treatment. In contrast, significant increases in the BBB leakage of sodium fluorescein, a much smaller molecule, were observed 1 and 2 days after the induction of colitis, in and around the circumventricular organs; the organum vasculosum of the lamina terminalis, subfornical organ and median eminence of the hypothalamus. TNBS-treated rats also exhibited sodium fluorescein leakage in focal areas in the brain parenchyma. The expression of endothelial barrier antigen, a protein associated with the BBB, was reduced about 60% 48 h after the induction of colitis. This returned to control values by 3 weeks, when colitis had largely subsided. In conclusion, experimental colitis transiently increased permeability of the brain to small molecules through a mild disruption of the BBB. 相似文献