Ghrelin projection from the lateral hypothalamus area to the dorsal vagal complex and its regulation of gastric motility in cisplatin-treated rats

Yanling Gong,Yang Liu,Yaoyao Guo,Manqing Su,Yifan Zhong,Luo Xu,Feifei Guo,Shengli Gao

doi:10.1016/j.npep.2017.09.003

Abstract

ObjectiveTo investigate ghrelin projection from the lateral hypothalamus area (LHA) to the dorsal vagal complex (DVC) and its regulation of gastric motility in cisplatin-treated rats. Materials and methodsIn the present study, the protein and mRNA expression of ghrelin and its receptor GHSR-1a were measured by Western blot and PCR, respectively. The ghrelin fiber projections arising from the LHA and projecting to the DVC were investigated by retrograde tracing combined with fluoro-immunohistochemical staining. The effects of ghrelin in the DVC, electrical stimulation of the LHA, and electrical lesion of the DVC on gastric motility were measured in cisplatin-treated rats. ResultsGhrelin fibers originating in the LHA projected to the DVC. The protein and mRNA expression of GHSR-1a was greater in cisplatin-treated rats than in saline-treated rats. Conversely, the expression of ghrelin in the LHA and DVC was reduced in cisplatin-treated rats. Cisplatin treatment also reduced gastric contractions. Ghrelin administrated into the DVC significantly promoted gastric motility, an effect completely blocked by treatment with the ghrelin receptor antagonist [D-Lys-3]-GHRP-6. In addition, electrical stimulation of the LHA promoted gastric motility, though this effect was much weaker in cisplatin-treated rats than in control rats. The excitatory effect of electrical stimulation of the LHA on gastric motility was partially blocked by pretreatment of the DVC with [D-Lys-3]-GHRP-6. Electrical lesion of the DVC diminished the excitatory effect that was induced by electrical stimulation of the LHA. ConclusionsDVC, especially AP, may have a role for gastric contraction induced by the stimulation of the LHA. This regulation on gastric motility was weaker in cisplatin-treated rats than in saline-treated rats, possibly due to reduced ghrelin expression in the LHA and ghrelin projection from the LHA to the DVC.

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