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        Chronic Stress Induces Neurotrophin-3 in Rat Submandibular Gland

        Juri Saruta,Keiichi Tsukinoki,Michitaro Iida,Yusuke Kondo,Masahiro To,Takashi Hayashi,Mayumi Hori,Sadao Sato 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.6

        Purpose: Plasma neurotrophin-3 (NT-3) levels are associated with several neural disorders. We previously reported that neurotrophins were released from salivary glands following acute immobilization stress. While the salivary glands were the source of plasma neurotrophins in that situation, the association between the expression of neurotrophins and the salivary gland under chronic stress conditions is not well understood. In the present study, we investigated whether NT-3 levels in the salivary gland and plasma were influenced by chronic stress. Materials and Methods: Expressions of NT-3 mRNA and protein were characterized, using real-time polymerase chain reactions, enzyme-linked immunosorbent assay, and immunohistochemistry,in the submandibular glands of male rats exposed to chronic stress (12 h daily for 22 days). Results: Plasma NT-3 levels were significantly increased by chronic stress (p<0.05), and remained elevated in bilaterally sialoadenectomized rats under the same condition. Since chronic stress increases plasma NT-3 levels in the sialoadenectomized rat model, plasma NT-3 levels were not exclusively dependent on salivary glands. Conclusion: While the salivary gland was identified in our previous study as the source of plasma neurotrophins during acute stress, the exposure to long-term stress likely affects a variety of organs capable of releasing NT-3 into the bloodstream. In addition, the elevation of plasma NT-3 levels may play important roles in homeostasis under stress conditions.

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        Effects of Stress on Mouse β-Defensin-3 Expression in the Upper Digestive Mucosa

        Rie Kawashima,Keiichi Tsukinoki,Tomoko Shimizu,Masahiro To,Juri Saruta,Yoshinori Jinbu,Mikio Kusama 연세대학교의과대학 2014 Yonsei medical journal Vol.55 No.2

        Purpose: Gastrointestinal integrity and immune surveillance are affected by stress. Stress also adversely affects mucosal barrier function. β-defensins constitute an integralcomponent of the innate immune system as antimicrobial peptides, serving as the first line of defense against microbial pathogens at the epithelial surfaces of the upper digestive mucosa. The primary objective of this study was to determine the effects of stress on the expression profile of mouse β-defensin-3 in the upper digestivemucosa of mice with diabetes. Materials and Methods: We established a mouse model of restraint stress by using NSY/Hos mice with type 2 diabetes mellitus. We used real-time polymerase chain reaction, in situ hybridization, and immunohistochemistryto investigate the effects of stress and glucocorticoid administrationon mouse β-defensin-3 expression in the upper digestive mucosa of the gingiva, esophagus, and stomach. Results: Mouse β-defensin-3 mRNA expression was higher in the esophagus than in the gingiva or stomach (p<0.05). In the esophagus, mouse β-defensin-3 mRNA expression was lower in stressed mice than in non-stressed mice (p<0.05). Furthermore, immunoreactivity to mouse β-defensin-3 proteinwas lower in the esophagus of stressed mice than non-stressed mice, consistent with the results of mRNA expression analysis. Systemic glucocorticoid administrationalso downregulated esophageal mouse β-defensin-3 mRNA expression. Conclusion:Our novel findings show that stress decreases mouse β-defensin-3 expressionin the esophagus of mice with diabetes, possibly due to increased endogenous glucocorticoid production. It appears to be highly likely that stress management may normalize mucosal antimicrobial defenses in patients with diabetes.

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