Ghrelin exhibited antidepressant and anxiolytic effect via the p38-MAPK signaling pathway in hippocampus

Publication date: Available online 8 March 2019Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Qiu-Qin Han, Hui-Jie Huang, Ya-Lin Wang, Liu Yang, Adam Pilot, Xiao-Cang Zhu, Rui Yu, Jing Wang, Xiao-Rong Chen, Qiong Liu, Bing Li, Gen-Cheng Wu, Jin YuAbstractGhrelin, a peptide derived from stomach, is an endogenous ligand for growth hormone secretagogue receptor (GHSR). So far, the exact role of ghrelin in depression and anxiety is still being debated. The p38 mitogen-activated protein kinase (p38-MAPK) is known to be activated in response to various stress stimuli. Thus, we hypothesize that ghrelin has an antidepressant effect, to which the p38-MAPK signaling pathway significantly contributes. To test this hypothesis, chronic social defeat stress (CSDS) was used as a model of depression. We employed the adeno-associated virus-mediated siRNA approach to down-regulate GHSR expression in the hippocampus of mice in vivo. Both ghrelin and the p38 inhibitor, SB203580, were administered to identify the effect of ghrelin on depressive-like behavior of stressed mice and to better assess the role of the p38-MAPK signaling pathway in this process. We found that CSDS activated the endogenous ghrelin-GHSR in hippocampal neurons, which possibly resulted in opposing the formation of depression- and anxiety-like behaviors in mice. Furthermore, the p38-MAPK signaling pathway had an important role in the antidepressant effect of ghrelin. Therefore, we conclude th...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research