PMID- 22460084
OWN - NLM
STAT- MEDLINE
DCOM- 20120807
LR  - 20211021
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 18
IP  - 4
DP  - 2012 Apr
TI  - Brain derived neurotrophic factor inhibits apoptosis in enteric glia during gut 
      inflammation.
PG  - BR117-22
AB  - BACKGROUND: Enteric glia cells (EGCs) are essential for the integrity of the 
      bowel. A loss of EGCs leads to a severe inflammation of the intestines. As a 
      diminished EGC network is postulated in Crohn's disease (CD), we aimed to 
      investigate if EGCs could be a target of apoptosis during inflammation in CD, 
      which can be influenced by Brain derived neurotrophic factor (BDNF). 
      MATERIAL/METHODS: GFAP, BDNF and cCaspase-3 were detected in the gut of patients 
      with CD. Primary EGC cultures were established and cultivated. Tyrosine receptor 
      kinase (TrkB) receptors on these cells were investigated by western blot and 
      immunofluorescence. Rate of apoptosis was induced by tumor necrosis factor 
      (TNF-alpha) and interferon (IFN-gamma). Apoptosis was determined by a 
      fluorometric caspase 3/7 activation assay after preincubation of these cells with 
      BDNF or neutralizing anti-BDNF antibodies. RESULTS: Mucosal GFAP-positive EGCs 
      undergo apoptosis revealed by cCaspase-3 in the gut of patients with CD 
      expressing BDNF highly. The combination of TNF-alpha and IFN-gamma was able to 
      induce apoptosis in primary EGCs, whereas these factors alone did not. Brain 
      derived neurotrophic factor (BDNF) attenuate glia cell apoptosis to a small 
      extent, but neutralizing antibodies against BDNF dramatically increased 
      apoptosis. CONCLUSIONS: Mucosal EGC apoptosis is an important finding in the gut 
      of patients with CD. Proinflammatory cytokines, which are highly increased in CD, 
      induce EGC apoptosis, whereas the neurotrophin BDNF might be protective for EGC. 
      Since EGCs are implicated in the maintenance of the enteric mucosal integrity, 
      EGC apoptosis may contribute to the pathophysiological changes in CD.
FAU - Steinkamp, Martin
AU  - Steinkamp M
AD  - Department of Gastroenterology, Endocrinology and Metabolism, University of 
      Marburg, Marburg, Germany.
FAU - Schulte, Nadine
AU  - Schulte N
FAU - Spaniol, Ulrike
AU  - Spaniol U
FAU - Pfluger, Carolin
AU  - Pfluger C
FAU - Hartmann, Christoph
AU  - Hartmann C
FAU - Kirsch, Joachim
AU  - Kirsch J
FAU - von Boyen, Georg B
AU  - von Boyen GB
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Nerve Growth Factors)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Adult
MH  - Apoptosis/*drug effects
MH  - Biopsy
MH  - Brain-Derived Neurotrophic Factor/metabolism/*pharmacology
MH  - Case-Control Studies
MH  - Caspase 3/metabolism
MH  - Colon/drug effects/metabolism/pathology
MH  - Crohn Disease/metabolism/pathology
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Fluorometry
MH  - Gastrointestinal Tract/drug effects/*metabolism/*pathology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Humans
MH  - Inflammation/metabolism/*pathology
MH  - Intestinal Mucosa/drug effects/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Nerve Growth Factors/metabolism
MH  - Neuroglia/drug effects/metabolism/*pathology
MH  - Receptor, trkB/metabolism
PMC - PMC3560818
EDAT- 2012/03/31 06:00
MHDA- 2012/08/08 06:00
PMCR- 2012/04/01
CRDT- 2012/03/31 06:00
PHST- 2012/03/31 06:00 [entrez]
PHST- 2012/03/31 06:00 [pubmed]
PHST- 2012/08/08 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - 882612 [pii]
AID - 10.12659/msm.882612 [doi]
PST - ppublish
SO  - Med Sci Monit. 2012 Apr;18(4):BR117-22. doi: 10.12659/msm.882612.