PMID- 25963324 OWN - NLM STAT- MEDLINE DCOM- 20150930 LR - 20181113 IS - 1573-2568 (Electronic) IS - 0163-2116 (Linking) VI - 60 IP - 8 DP - 2015 Aug TI - Brain-Derived Neurotrophic Factor Contributes to Colonic Hypermotility in a Chronic Stress Rat Model. PG - 2316-26 LID - 10.1007/s10620-015-3695-8 [doi] AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) has prokinetic effects on gut motility and is increased in the colonic mucosa of irritable bowel syndrome. AIMS: We aimed to investigate the possible involvement of BDNF in stress-induced colonic hypermotility. METHODS: Male Wistar rats were exposed to daily 1-h water avoidance stress (WAS) or sham WAS for 10 consecutive days. The presence of BDNF and substance P (SP) in the colonic mucosa was determined using enzyme immunoassay kits. Immunohistochemistry and western blotting were performed to assess the expression of BDNF and its receptor, TrkB. The contractions of muscle strips were studied in an organ bath system. RESULTS: Repeated WAS increased the fecal pellet expulsion and spontaneous contractile activities of the colonic muscle strips. Both BDNF and SP in the colonic mucosa were elevated following WAS. Immunohistochemistry revealed the presence of BDNF and TrkB in the mucosa and myenteric plexus. BDNF and TrkB were both up-regulated in colon devoid of mucosa and submucosa from the stressed rats compared with the control. BDNF pretreatment caused an enhancement of the SP-induced contraction of the circular muscle (CM) strips. TrkB antibody significantly inhibited the contraction of the colonic muscle strips and attenuated the excitatory effects of SP on contractions of the CM strips. Repeated WAS increased the contractile activities of the CM strips induced by SP after BDNF pretreatment, and this effect was reversed by TrkB antibody. CONCLUSIONS: The colonic hypermotility induced by repeated WAS may be associated with the increased expression of endogenous BDNF and TrkB. BDNF may have potential clinical therapeutic use in modulating gut motility. FAU - Quan, Xiaojing AU - Quan X AD - Department of Gastroenterology, Renmin Hospital of Wuhan University, Number 238, Jiefang Road, Wuhan, 430060, Hubei Province, China, quanxiaojing77@126.com. FAU - Luo, Hesheng AU - Luo H FAU - Fan, Han AU - Fan H FAU - Tang, Qincai AU - Tang Q FAU - Chen, Wei AU - Chen W FAU - Cui, Ning AU - Cui N FAU - Yu, Guang AU - Yu G FAU - Xia, Hong AU - Xia H LA - eng PT - Journal Article DEP - 20150512 PL - United States TA - Dig Dis Sci JT - Digestive diseases and sciences JID - 7902782 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 33507-63-0 (Substance P) SB - IM MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/metabolism/*physiology MH - Colon/*physiology MH - Gastrointestinal Motility/*physiology MH - Immunohistochemistry MH - In Vitro Techniques MH - Intestinal Mucosa/metabolism MH - Male MH - Membrane Glycoproteins/physiology MH - Models, Animal MH - Muscle Contraction/physiology MH - Muscle, Smooth/physiology MH - Rats, Wistar MH - Stress, Psychological MH - Substance P/metabolism MH - Up-Regulation/physiology EDAT- 2015/05/13 06:00 MHDA- 2015/10/01 06:00 CRDT- 2015/05/13 06:00 PHST- 2014/12/28 00:00 [received] PHST- 2015/04/29 00:00 [accepted] PHST- 2015/05/13 06:00 [entrez] PHST- 2015/05/13 06:00 [pubmed] PHST- 2015/10/01 06:00 [medline] AID - 10.1007/s10620-015-3695-8 [doi] PST - ppublish SO - Dig Dis Sci. 2015 Aug;60(8):2316-26. doi: 10.1007/s10620-015-3695-8. Epub 2015 May 12.