Apoptosis in enteric glia:Part of the puzzle in Crohn’s disease?

Abstract

SummaryBackgroundEnteric 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/MethodsGFAP, 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-α) and interferon (IFN-γ). Apoptosis was determined by a fluorometric caspase 3/7 activation assay after preincubation of these cells with BDNF or neutralizing anti-BDNF antibodies.ResultsMucosal GFAP-positive EGCs undergo apoptosis revealed by cCaspase-3 in the gut of patients with CD expressing BDNF highly. The combination of TNF-α and IFN-γ 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.ConclusionsMucosal 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.

Relation between Selected Sleep Parameters, Depression, Anti-Tumor Necrosis Factor Therapy, and the Brain-Derived Neurotrophic Factor Pathway in Inflammatory Bowel Disease

“…Interestingly, a positive correlation between proBDNF and BDNF levels was also noted, which implies that in IBD patients, the equilibrium between these two forms is maintained. These results are in line with the data obtained by other authors [ 37 , 38 ]. As Steinkampf et al have demonstrated, inflammation might cause an increase in BDNF production in the enteric glial cells (EGC), the main source of NTs in the gut [ 37 ].…”

“…These results are in line with the data obtained by other authors [ 37 , 38 ]. As Steinkampf et al have demonstrated, inflammation might cause an increase in BDNF production in the enteric glial cells (EGC), the main source of NTs in the gut [ 37 ]. Moreover, EGCs also express TrkB receptors, which could suggest the existence of an autocrine loop, possibly disrupted in the course of the IBD [ 37 ].…”

Diagnostic Significance of Serum Levels of Nerve Growth Factor and Brain Derived Neurotrophic Factor in Diabetic Peripheral Neuropathy

“…In addition, a previous study illustrated that the reduced BDNF expression in diabetic rat brain endothelium in vivo is regarded as an increased risk of neuronal injury, and also pointed out the correlation of suppressed BDNF expression in diabetes with neuron injury [ 34 ], just as in our study. Furthermore, it has been demonstrated that BDNF protects enteric glia cells from apoptosis during inflammation in Crohn’s disease [ 35 ]. All of these findings revealed that an elevated BDNF level plays a positive role in DPN treatment.…”

Electroacupuncture and Moxibustion Modulate the BDNF and TrkB Expression in the Colon and Dorsal Root Ganglia of IBS Rats with Visceral Hypersensitivity

“…After being synthesized in primary sensory neurons, BDNF is transported to the primary afferent nerve terminals of the spinal cord dorsal horn, where it is involved in the regulation of pain hypersensitivity caused by different pain stimuli [ 6 ]. BDNF does not only present in the nervous system but also expresses in peripheral tissues, such as the intestine and pancreas [ 7 , 8 ], and especially in the intestinal epithelium, myenteric plexus, and submucosal plexus of the colon. The fecal supernatants (FSN) from diarrhea-predominant IBS patients significantly increase BDNF mRNA and protein levels in colonic epithelial cells of humans and mice [ 9 ].…”