title: Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito.
abstract: Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6-7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation) was performed 1-2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92-86% suppression of food intake at 2-24 h post-surgery compared with control group (no surgery). RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration) and satiety (meal interval) and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition. RKT improves food consumption post-surgically that may involve modulation of pain pathway.
authors.affiliation: CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Mogami
authors.affiliation: CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yakabi
authors.affiliation: CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Karasawa
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yakabi
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hattori
authors.affiliation: CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000005:Abdomen / Q000473:pathology / Q000601:surgery*; D000284:Administration, Oral; D000818:Animals; D000855:Anorexia / Q000188:drug therapy; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D004435:Eating / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D054439:Ghrelin / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D010936:Plant Extracts / Q000008:administration & dosage*; D010946:Plants, Medicinal; D011183:Postoperative Complications / Q000188:drug therapy / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000276:immunology / Q000378:metabolism; D012527:Satiation / Q000187:drug effects; D012528:Satiety Response / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D054439:Ghrelin; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; C084136:liu-jun-zi-tang; D014446:Tyrosine 3-Monooxygenase