3区 · 综合性期刊
ArticleOA
作者: Yada, Toshihiko ; Cheng, Kai-Chun ; Yahiro, Kinnosuke ; Nakamura, Norifumi ; Inui, Akio ; Ataka, Koji ; Yokoyama, Yoshito ; Ushikai, Miharu ; Yamamoto, Katsuhiro ; Asakawa, Akihiro ; Kojima, Masayasu ; Iwai, Haruki ; Arai, Takeshi ; Suzuki, Hajime ; Yagi, Takakazu ; Hirayama, Toshiya
Abstract:Helicobacter pylori (Hp) infection is related to the pathogenesis of chronic gastric disorders and extragastric diseases. Here, we examined the anorexigenic and anxiogenic effects of Hp vacuolating cytotoxin A (VacA) through activation of hypothalamic urocortin1 (Ucn1). VacA was detected in the hypothalamus after peripheral administration and increased Ucn1 mRNA expression and c-Fos-positive cells in the hypothalamus but not in the nucleus tractus solitarius. c-Fos and Ucn1-double positive cells were detected. CRF1 and CRF2 receptor antagonists suppressed VacA-induced anxiety and anorexia, respectively. VacA activated single paraventricular nucleus neurons and A7r5 cells; this activation was inhibited by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. VacA causes anorexia and anxiety through the intracellular PLC-PKC pathway, migrates across the blood-brain barrier, and activates the Ucn1-CRF receptor axis.