title: High-Dose Radiation-Induced Changes in Murine Small Intestinal Motility: Are the Changes in the Interstitial Cells of Cajal or in the Enteric Nervous System?
abstract: Murine small intestinal motility consists of phasic contraction from interstitial cells of Cajal (ICC) and migrating motor complexes (MMCs) from the enteric nervous system. The number of ICC is reduced in various gastrointestinal disorders, and this effect can be reversed once the disorder is resolved through cellular and tissue remodelling. Exposure to high-dose radiation can induce inflammation and alter intestinal motility. In this study, we investigated the changes in the small intestinal motility of 8- to 10-week-old male C3H/HeN mice after high-dose (13 Gy) irradiation. The aim of this study was to determine whether those changes are caused by changes in the ICC or enteric nervous system. After irradiation, the small intestine was dissected and stored in oxygenated Krebs-Ringer bicarbonate solution. The tension of contractions and intracellular membrane potentials were recorded at day 0, 1, 3 and 5 after irradiation and compared with those of sham-irradiated mice. Histological evaluation was performed by immunohistochemistry and apoptosis was evaluated. Quantitative real-time polymerase chain reaction (qPCR) for c-kit mRNA was also performed. Phasic contractions were not changed at day 0, 1, 3 and 5 after irradiation and did not significantly differ from those in the control mice. Slow waves were also sustained after irradiation. However, the frequency of migrating motor complexes (MMCs) was significantly higher at day 0 and 1 after exposure and the amplitude and area under the curve were significantly lower at day 3 after exposure compared with control mice. MMCs were recovered at day 5 with no difference from those of the control mice. ICC were detected after irradiation by immunohistochemistry for c-kit, and c-kit mRNA levels did not differ between sham-irradiated and irradiated mice. Histological evaluation showed that the most severe inflammation was detected at day 3 after irradiation, and apoptosis was detected only in the mucosa. Acetylcholine increased the contractility after irradiation, and tetrodotoxin decreased the number of MMCs in sham-irradiated and irradiated mice. N(w)-oxide-l-arginine (L-NA) increased the number of MMCs. MMCs were recovered after L-NA treatment at day 3 after irradiation. Sodium nitroprusside decreased the MMCs in sham-irradiated and irradiated mice. Exposure to high-dose radiation did not alter phasic contractions and slow waves in the small intestine of mice, which suggests that ICC and their functions may be sustained after high-dose irradiation. Mucosal inflammation was severe after irradiation and there were some changes in MMCs related to the enteric nervous system.
authors.affiliation: a  Division of Colorectal Surgery, Department of Surgery, Departments of.
authors.forename: Seung-Bum
authors.initials: SB
authors.lastname: Ryoo
authors.affiliation: d  Research Center and.
authors.forename: Joong-Sun
authors.initials: JS
authors.lastname: Kim
authors.affiliation: e  Department of Pathology, Dongnam Institute of Radiological and Medical Sciences, Busan, Republic of Korea; and.
authors.forename: Min-Seouk
authors.initials: MS
authors.lastname: Kim
authors.affiliation: b  Radiation Oncology and.
authors.forename: Kyubo
authors.initials: K
authors.lastname: Kim
authors.affiliation: a  Division of Colorectal Surgery, Department of Surgery, Departments of.|c  Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea;
authors.forename: Seung A
authors.initials: SA
authors.lastname: Yu
authors.affiliation: d  Research Center and.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Bae
authors.affiliation: a  Division of Colorectal Surgery, Department of Surgery, Departments of.
authors.forename: Heung-Kwon
authors.initials: HK
authors.lastname: Oh
authors.affiliation: a  Division of Colorectal Surgery, Department of Surgery, Departments of.
authors.forename: Sang Hui
authors.initials: SH
authors.lastname: Moon
authors.affiliation: a  Division of Colorectal Surgery, Department of Surgery, Departments of.|f  Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choe
authors.affiliation: c  Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea;
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.affiliation: a  Division of Colorectal Surgery, Department of Surgery, Departments of.
authors.forename: Kyu Joo
authors.initials: KJ
authors.lastname: Park
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D017615:Enteric Nervous System / Q000502:physiology* / Q000528:radiation effects; D005769:Gastrointestinal Motility / Q000502:physiology* / Q000528:radiation effects; D007421:Intestine, Small / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009119:Muscle Contraction / Q000502:physiology* / Q000528:radiation effects; D011829:Radiation Dosage; D000069079:Radiation Exposure; D000067170:Telocytes / Q000502:physiology* / Q000528:radiation effects