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.
[1]Shanghai Univ Med & Hlth Sci, Shanghai Key Lab Mol Imaging, Shanghai 201318, Peoples R China.
[2]Fudan Univ, Shanghai Med Coll, Dept Integrat Med & Neurobiol,Brain Sci Collabora, State Key Lab Med Neurobiol,Sch Basic Med Sci,Ins, 130 Dongan Rd, Shanghai 200032, Peoples R China.
[3]Univ Chinese Acad Sci, Sino Danish Coll, Beijing 100049, Peoples R China.
[4]Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Anat Histol & Embryol, Shanghai 200032, Peoples R China.
[5]Key Lab Med Imaging Comp & Comp Assisted Interven, Shanghai 200032, Peoples R China.
[6]Fudan Univ, Ctr Labs, Jinshan Hosp, Shanghai 201508, Peoples R China.
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