Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice.

Scientific reports 2019 Apr 12

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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.

Citation

Hajime Suzuki, Koji Ataka, Akihiro Asakawa, Kai-Chun Cheng, Miharu Ushikai, Haruki Iwai, Takakazu Yagi, Takeshi Arai, Kinnosuke Yahiro, Katsuhiro Yamamoto, Yoshito Yokoyama, Masayasu Kojima, Toshihiko Yada, Toshiya Hirayama, Norifumi Nakamura, Akio Inui. Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice. Scientific reports. 2019 Apr 12;9(1):6011