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.
Highlights
Www.nature.com/scientificreports orexigenic peptide produced in the stomach, and it shares a close relationship with the brain-gut axis[10]
The delta delta CT (2−ΔΔCT) value for Ucn[1] was 3.956 in the hypothalamus of mice subjected to IP administration of Vacuolating cytotoxin A (VacA), which was significantly higher than the level in the vehicle-administered control group (Fig. 2d)
Our present study demonstrated that chronic Hp infection decreased both body weight and food intake in an animal model
Summary
Www.nature.com/scientificreports orexigenic peptide produced in the stomach, and it shares a close relationship with the brain-gut axis[10]. Various gastrointestinal disorders have been reported to increase comorbidity in psychiatric disorders[14,15], and central neuromodulators, which are used to treat depression and anxiety, have been used to treat gastrointestinal symptoms based on the gut-brain interaction[16]. VacA induces the formation of large vacuoles in the cytoplasm, mitochondrial-dependent apoptosis and autophagy of epithelial cells, and the inhibition of T cell proliferation[21]. Both VacA and serum VacA antibodies are associated with an increased risk of gastroduodenal ulcers and gastric cancer[25,26]. The aims of this study were to confirm the anorexigenic and anxiogenic effects of Hp VacA and its mechanisms of action using animal models
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