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The GDNF System Is Altered in Diverticular Disease - Implications for Pathogenesis
Martina Böttner1, Martina Barrenschee, Ines Hellwig
1Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Plos One
|June 28, 2013
Summary
Glial cell line-derived neurotrophic factor (GDNF) is crucial for gut innervation. Diverticular disease (DD) patients show reduced GDNF signaling, suggesting a lack of neurotrophic support contributes to enteric neuronal loss.
Area of Science:
- Gastroenterology
- Neuroscience
- Molecular Biology
Background:
- Glial cell line-derived neurotrophic factor (GDNF) absence causes intestinal aganglionosis.
- Diverticular disease (DD) patients exhibit hypoganglionosis, indicating potential neurotrophic factor deprivation.
- The GDNF system's role in DD pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the mRNA expression of the GDNF system in diverticular disease.
- To examine the effects of GDNF on cultured enteric neurons.
Main Methods:
- Colonic specimens from DD patients and controls were analyzed for GDNF system mRNA expression.
- Laser-microdissected samples of myenteric ganglia and intestinal muscle layers were used for qPCR.
- Effects of GDNF on cultured enteric neurons, including receptor expression and neuronal differentiation, were monitored.
Main Results:
- GDNF and its receptor mRNA expression were significantly downregulated in the muscularis propria of DD patients.
- GDNF was highly expressed in muscle layers, while its receptors were found in myenteric ganglia.
- GDNF treatment enhanced receptor expression, neuronal differentiation, and plasticity in cultured enteric neurons.
Conclusions:
- The GDNF system is compromised in diverticular disease.
- GDNF promotes enteric neuronal differentiation and plasticity.
- Enteric neuronal loss in DD may result from insufficient neurotrophic support via the GDNF system.
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