PMID- 25164090
OWN - NLM
STAT- MEDLINE
DCOM- 20150616
LR  - 20141006
IS  - 1748-1716 (Electronic)
IS  - 1748-1708 (Linking)
VI  - 212
IP  - 3
DP  - 2014 Nov
TI  - Brain-derived neurotrophic factor accelerates gut motility in slow-transit 
      constipation.
PG  - 226-38
LID - 10.1111/apha.12374 [doi]
AB  - BACKGROUND & AIMS: Brain-derived neurotrophic factor (BDNF) may play a critical 
      role in gut motility. We aimed to investigate BDNF's physiologic effects on gut 
      motility in slow-transit constipation (STC) and to explore the underlying 
      molecular mechanisms. METHODS: BDNF expression and alterations of colonic nerve 
      fibre density in STC patients were first investigated. BDNF's effects on 
      gastrointestinal motility of both BDNF(+/-) mice and loperamide-induced 
      constipation mice were then examined in vivo and in vitro. Smooth muscle alpha-actin 
      (alpha-SMA) expression, and nerve fibre, neuromuscular junction (NMJ) and smooth 
      muscle cell (SMC) alterations were investigated. Finally, the effects of 
      BDNF-induced TrkB-phospholipase C/inositol trisphosphate (TrkB-PLC/IP3) pathway 
      activation on gut motility were investigated. RESULTS: In STC patients, BDNF 
      expression and nerve fibre density were decreased, and mucosal nerve fibre 
      ultrastructural degenerations were demonstrated. Gut motility was decreased in 
      vivo and in vitro in BDNF(+/-) and constipation mice, with BDNF dose-dependently 
      increasing gut motility. In BDNF(+/-) mice, alpha-SMA expression and nerve fibre 
      density were decreased, and nerve fibre, NMJ and SMC ultrastructural 
      degenerations were observed. Finally, TrkB-PLC/IP3 pathway antagonists 
      dramatically attenuated BDNF's excitatory effect on gut motility, and exogenous 
      BDNF induced an obvious increase in IP3 expression. CONCLUSIONS: BDNF plays an 
      important regulatory role in gut motility in STC. It was mediated by altering the 
      intestinal innervation structure, as well as smooth muscle secondary degeneration 
      through a mechanism involving TrkB-PLC/IP3 pathway activation.
CI  - (c) 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
FAU - Chen, F
AU  - Chen F
AD  - Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China; 
      Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, 
      Jinan, China.
FAU - Yu, Y
AU  - Yu Y
FAU - Wang, P
AU  - Wang P
FAU - Dong, Y
AU  - Dong Y
FAU - Wang, T
AU  - Wang T
FAU - Zuo, X
AU  - Zuo X
FAU - Li, Y
AU  - Li Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140918
PL  - England
TA  - Acta Physiol (Oxf)
JT  - Acta physiologica (Oxford, England)
JID - 101262545
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.1.4.- (Type C Phospholipases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/deficiency/genetics/*metabolism
MH  - Colon/metabolism
MH  - Constipation/*metabolism
MH  - Female
MH  - Gastrointestinal Motility/genetics/*physiology
MH  - Humans
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Neurons/metabolism
MH  - Receptor, trkB/*metabolism
MH  - Signal Transduction/physiology
MH  - Type C Phospholipases/metabolism
OTO - NOTNLM
OT  - BDNF
OT  - STC
OT  - TrkB-PLC/IP3 pathway
OT  - gut motility
OT  - nerve fibre
EDAT- 2014/08/29 06:00
MHDA- 2015/06/17 06:00
CRDT- 2014/08/29 06:00
PHST- 2013/12/06 00:00 [received]
PHST- 2014/03/18 00:00 [revised]
PHST- 2014/07/29 00:00 [revised]
PHST- 2014/08/23 00:00 [accepted]
PHST- 2014/08/29 06:00 [entrez]
PHST- 2014/08/29 06:00 [pubmed]
PHST- 2015/06/17 06:00 [medline]
AID - 10.1111/apha.12374 [doi]
PST - ppublish
SO  - Acta Physiol (Oxf). 2014 Nov;212(3):226-38. doi: 10.1111/apha.12374. Epub 2014 
      Sep 18.