Rapamycin Attenuates Anxiety and Depressive Behavior Induced by Helicobacter pylori in Association with Reduced Circulating Levels of Ghrelin

Abstract

Background. Helicobacter pylori (H. pylori) infection is closely associated with depression and development of neuroinflammation. The aim of this study is to explore the relationship between H. pylori, depression, and circulating levels of ghrelin. Methods. Mice were randomly divided into three groups: healthy control group (gavaged sterile saline and injected with saline, $n=8$ ); H. pylori+saline group (gavaged H. pylori and injected with saline, $n=8$ ); and H. pylori+rapa group (gavaged H. pylori and injected with rapamycin, $n=8$ ). Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were used for anxiety and depressive behavior test. Western blotting was utilized to assess mTOR, p-mTOR, and GSMD expression, and serum ghrelin levels were estimated using ELISA. Results. In the OFT, the control mice moved more and exhibited a increase in crossing number relative to the H. pylori+saline mice (all $P<0.05$ ). Increased quantity of fecal boli can be indicative of increased anxiety and emotionality of the subject animal. H. pylori+saline mice exhibited an increase in fecal boli when compared to control mice and H. pylori+rapa mice ( $P<0.05$ ). H. pylori infected mice decreasing the expression of ghrelin. The protein levels of p-mTOR/mTOR in the gastric antrum mTOR signaling activation and low-level ghrelin in H. pylori-infect mice compared to those in control mice (all P <0.001). Compared with single H. pylori infection, mTOR inhibitors increased the ghrelin secretion of H. pylori infection to a certain extent ( $P<0.05$ ). The protein levels of GSDMD expression significantly increase in hippocampus of H. pylori-infected mice ( $P<0.001$ ). Rapamycin treatment inhibited expression of GSDMD in H. pylori-infected mice ( $P<0.05$ ). Conclusions. H. pylori infection is associated with increased expression of mTOR and decreased circulating levels of ghrelin. Elevated pyroptosis in the brain and anxiety- and depressed-like behaviors occur when ghrelin levels are suppressed.