Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice.
Hajime SuzukiKoji AtakaAkihiro AsakawaKai-Chun ChengMiharu UshikaiHaruki IwaiTakakazu YagiTakeshi AraiKinnosuke YahiroKatsuhiro YamamotoYoshito YokoyamaMasayasu KojimaToshihiko YadaToshiya HirayamaNorifumi NakamuraAkio InuiPublished in: Scientific reports (2019)
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.
Keyphrases
- helicobacter pylori
- induced apoptosis
- helicobacter pylori infection
- cell cycle arrest
- protein kinase
- oxidative stress
- endoplasmic reticulum stress
- sleep quality
- signaling pathway
- cell death
- physical activity
- metabolic syndrome
- spinal cord
- cell proliferation
- insulin resistance
- high glucose
- skeletal muscle
- pi k akt
- depressive symptoms
- diabetic rats