Ghrelin exhibited antidepressant and anxiolytic effect via the p38-MAPK signaling pathway in hippocampus.
Ghrelin, 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 that ghrelin may reduce CSDS-induced depression- and anxiety-like behaviors via inhibiting the p38-MAPK signaling pathway in hippocampal neurons of mice.
['Han|Qiu-Qin|QQ|', 'Huang|Hui-Jie|HJ|', 'Wang|Ya-Lin|YL|', 'Yang|Liu|L|', 'Pilot|Adam|A|', 'Zhu|Xiao-Cang|XC|', 'Yu|Rui|R|', 'Wang|Jing|J|', 'Chen|Xiao-Rong|XR|', 'Liu|Qiong|Q|', 'Li|Bing|B|', 'Wu|Gen-Cheng|GC|', 'Yu|Jin|J|']
D000818:Animals D014151:Anti-Anxiety Agents D000928:Antidepressive Agents D001007:Anxiety D003863:Depression D004195:Disease Models, Animal D055785:Gene Knockdown Techniques D054439:Ghrelin D006624:Hippocampus D007093:Imidazoles D020935:MAP Kinase Signaling System D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D011725:Pyridines
Ghrelin Depression P38 Chronic social defeat stress (CSDS)