Involvements of the lateral hypothalamic area in gastric motility and its regulation by the lateral septum

Abstract

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) pre-dominantly produced in the stomach. Recent studies have shown that it may promote food intake and gastric motility. We aim to explore effects of ghrelin on the gastric distension (GD) sensitive neurons and gastric motility in the lateral hypothalamic area (LHA), and the possible regulation by the lateral septum. Extracellular single unit discharges were recorded and the gastric motility was monitored by administration of ghrelin into LHA and electrical stimulation of lateral septum. Expression of GHS-R was determined by polymerase chain reaction (PCR), western blot and immunohistochemistry staining. Projection of nerve fiber and expression of ghrelin were observed by retrograde tracer and fluo-immunohistochemistry staining. Results revealed that there were GD neurons in the LHA, and administration of ghrelin could excite both GD-excitatory (GD-E) and GD-inhibited (GD-I) neurons in the LHA. The gastric motility was significantly promoted by administration of ghrelin into LHA with a dose dependent manner, which could be completely abolished by treatment with ghrelin receptor antagonist [D-Lys-3]-GHRP-6 or BIM-28163. c-Fos expression was significantly increased after ghrelin administration to the LHA. Electrical stimulation of the lateral septum could significantly excite GD neurons responsive to ghrelin in the LHA as well as promote gastric motility. However, those effects could be absorbed by pre-treatment of [D-Lys-3]-GHRP-6. GHSR-1a expression in the LHA had no change after ghrelin administration to the LHA or electrical stimulating lateral septum. Electrical lesion of the LHA resulted in the decrease of gastric motility. GHS-R and Ghrelin/FG-double labeled neurons were observed in the LHA and lateral septum, respectively. It is suggested that the LHA may involve in promoting gastric motility via ghrelin. The Lateral septum projects to the LHA and exerts some regulating function on the LHA.

Keywords: Gastric distension responsive neurons; Gastric motility; Ghrelin; Lateral hypothalamic area; Lateral septum.