title: Ghrelin fibers from lateral hypothalamus project to nucleus tractus solitaries and are involved in gastric motility regulation in cisplatin-treated rats.
abstract: Ghrelin can alleviate cancer chemotherapy-induced dyspepsia in rodents, though the neural mechanisms involved are not known. Therefore, ghrelin projections from the lateral hypothalamus (LH) and its involvement in the regulation of gastric motility in cisplatin-treated rats were investigated with a multi-disciplined approach. Retrograde tracing combined with fluoro-immunohistochemical staining were used to investigate ghrelin fiber projections arising from LH and projecting to nucleus tractus solitaries (NTS). Results revealed that ghrelin fibers originating in LH project to NTS. Expression of ghrelin and its receptor growth hormone secretagogue receptor (GHS-R1a) in LH and NTS were detected by Western Blot. 2days after cisplatin dosing, expression of ghrelin in LH decreased while GHS-R1a in both LH and NTS increased. In electrophysiological experiments, the effects of N-methyl-d-aspartate (NMDA) microinjection in LH on neuronal discharge of gastric distension-responsive neurons in NTS and gastric motility were assessed. NMDA in LH excited most of ghrelin-responsive gastric distension (GD)-sensitive neurons in NTS and promoted gastric motility. This effect was partially blocked by ghrelin antibody in NTS. Furthermore, the excitatory effects of NMDA in cisplatin-treated rats were weaker than those in saline-treated rats. Behaviorally, cisplatin induced a significant increase of kaolin consumption and decrease of food intake. These studies reveal a decreased expression of ghrelin in LH and up-regulation of GHS-R1a in LH and NTS, which are involved in the regulation of GD neuronal discharge in NTS and gastric motility.
authors.affiliation: Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China. Electronic address: hanyu_ma@126.com.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China. Electronic address: xu.luo@163.com.
authors.forename: Luo
authors.initials: L
authors.lastname: Xu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007616:Kaolin; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000378:metabolism; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D054439:Ghrelin; D018377:Neurotransmitter Agents; D054440:Receptors, Ghrelin; D007616:Kaolin; D016202:N-Methylaspartate; D002945:Cisplatin
keywords: Cisplatin; Gastric distension responsive neurons; Gastric motility; Ghrelin; Lateral hypothalamus; Nucleus tractus solitaries