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Structural alterations of the intestinal epithelial barrier in Parkinson's disease.

Clairembault T, Leclair-Visonneau L, Coron E, Bourreille A, Le Dily S, Vavasseur F, Heymann MF, Neunlist M, Derkinderen P - Acta Neuropathol Commun (2015)

Bottom Line: The expression and localization of the two tight junctions proteins ZO-1 and occludin were analyzed by Western blot and immunofluorescence, respectively.The para- and transcellular permeability were not different between PD patients and controls.Our findings provide evidence that the IEB is morphologically altered in PD and further reinforce the potential role of the gastrointestinal tract in the initiation and/or the progression of the disease.

View Article: PubMed Central - PubMed

ABSTRACT
Functional and morphological alterations of the intestinal epithelial barrier (IEB) have been consistently reported in digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. There is mounting evidence that Parkinson's disease (PD) is not only a brain disease but also a digestive disorder. Gastrointestinal involvement is a frequent and early event in the course of PD, and it may be critically involved in the early development of the disease. We therefore undertook the present survey to investigate whether changes in the IEB function and/or morphology occur in PD. Colonic biopsies were performed in 31 PD patients and 11 age-matched healthy controls. The para- and transcellular permeability were evaluated by measuring sulfonic acid and horseradish peroxidase flux respectively, in colonic biopsies mounted in Ussing chambers. The expression and localization of the two tight junctions proteins ZO-1 and occludin were analyzed by Western blot and immunofluorescence, respectively. The para- and transcellular permeability were not different between PD patients and controls. The expression of occludin, but not ZO-1, was significantly lower in colonic samples from PD patients as compared to controls and the cellular distribution of both proteins was altered in colonic mucosal specimens from PD patients. Our findings provide evidence that the IEB is morphologically altered in PD and further reinforce the potential role of the gastrointestinal tract in the initiation and/or the progression of the disease.

No MeSH data available.


Related in: MedlinePlus

Localization of TJs proteins in the colonic mucosa of healthy controls (CTRL) and patients with Parkinson’s disease (PD). Representative photomicrographs of the colonic mucosa labeled with antibodies against ZO-1 (A, B) and occludin (C, D) in the colonic mucosa of control and PD patients; scale bar: 100 μm. High-magnification image of each area marked by red square; scale bar: 10 μm.
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Fig4: Localization of TJs proteins in the colonic mucosa of healthy controls (CTRL) and patients with Parkinson’s disease (PD). Representative photomicrographs of the colonic mucosa labeled with antibodies against ZO-1 (A, B) and occludin (C, D) in the colonic mucosa of control and PD patients; scale bar: 100 μm. High-magnification image of each area marked by red square; scale bar: 10 μm.

Mentions: The cellular distribution of occludin and ZO-1 was further investigated by immunofluorescence in 8 controls and 31 PD subjects. Samples from 3 controls were excluded because the mucosa was too small and/or too damaged to allow a reliable analysis of the TJs morphology. A mean of 96.4 crypts per biopsy were analyzed. We observed differences in the cellular distribution of both ZO-1 and occludin between PD patients and controls (Figure 4). A normal and typical reticular pattern of occludin and ZO-1 staining was observed in the colonic samples of 6 out of 8 controls (Figure 4A and C, Additional file 1) and in only 9/31 PD patients (Figure 4B and D, Additional file 1). TJs morphology was disrupted and irregularly distributed in the mucosa of 1 out of 8 controls (Figure 4A and C, Additional file 1) and in 14/31 PD patients (Figure 4B and D, Additional file 1). An occasional and mild disruption of TJs morphology was observed in the remaining control subject and in 8/31 PD samples (Figure 4 and Additional file 1). An increased staining of occludin in the cytoplasm of colonic enterocytes, suggestive of protein internalization, was observed in PD samples as opposed to the healthy group where occludin was mostly located in the TJs (Figure 4C and D). Worthy of note was the presence of moderate to severe TJs disorganization in the 5 patients who had never received levodopa, suggesting that the altered TJs morphology was not related to chronic levodopa intake (Additional file 2 and Table 1).Figure 4


Structural alterations of the intestinal epithelial barrier in Parkinson's disease.

Clairembault T, Leclair-Visonneau L, Coron E, Bourreille A, Le Dily S, Vavasseur F, Heymann MF, Neunlist M, Derkinderen P - Acta Neuropathol Commun (2015)

Localization of TJs proteins in the colonic mucosa of healthy controls (CTRL) and patients with Parkinson’s disease (PD). Representative photomicrographs of the colonic mucosa labeled with antibodies against ZO-1 (A, B) and occludin (C, D) in the colonic mucosa of control and PD patients; scale bar: 100 μm. High-magnification image of each area marked by red square; scale bar: 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4353469&req=5

Fig4: Localization of TJs proteins in the colonic mucosa of healthy controls (CTRL) and patients with Parkinson’s disease (PD). Representative photomicrographs of the colonic mucosa labeled with antibodies against ZO-1 (A, B) and occludin (C, D) in the colonic mucosa of control and PD patients; scale bar: 100 μm. High-magnification image of each area marked by red square; scale bar: 10 μm.
Mentions: The cellular distribution of occludin and ZO-1 was further investigated by immunofluorescence in 8 controls and 31 PD subjects. Samples from 3 controls were excluded because the mucosa was too small and/or too damaged to allow a reliable analysis of the TJs morphology. A mean of 96.4 crypts per biopsy were analyzed. We observed differences in the cellular distribution of both ZO-1 and occludin between PD patients and controls (Figure 4). A normal and typical reticular pattern of occludin and ZO-1 staining was observed in the colonic samples of 6 out of 8 controls (Figure 4A and C, Additional file 1) and in only 9/31 PD patients (Figure 4B and D, Additional file 1). TJs morphology was disrupted and irregularly distributed in the mucosa of 1 out of 8 controls (Figure 4A and C, Additional file 1) and in 14/31 PD patients (Figure 4B and D, Additional file 1). An occasional and mild disruption of TJs morphology was observed in the remaining control subject and in 8/31 PD samples (Figure 4 and Additional file 1). An increased staining of occludin in the cytoplasm of colonic enterocytes, suggestive of protein internalization, was observed in PD samples as opposed to the healthy group where occludin was mostly located in the TJs (Figure 4C and D). Worthy of note was the presence of moderate to severe TJs disorganization in the 5 patients who had never received levodopa, suggesting that the altered TJs morphology was not related to chronic levodopa intake (Additional file 2 and Table 1).Figure 4

Bottom Line: The expression and localization of the two tight junctions proteins ZO-1 and occludin were analyzed by Western blot and immunofluorescence, respectively.The para- and transcellular permeability were not different between PD patients and controls.Our findings provide evidence that the IEB is morphologically altered in PD and further reinforce the potential role of the gastrointestinal tract in the initiation and/or the progression of the disease.

View Article: PubMed Central - PubMed

ABSTRACT
Functional and morphological alterations of the intestinal epithelial barrier (IEB) have been consistently reported in digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. There is mounting evidence that Parkinson's disease (PD) is not only a brain disease but also a digestive disorder. Gastrointestinal involvement is a frequent and early event in the course of PD, and it may be critically involved in the early development of the disease. We therefore undertook the present survey to investigate whether changes in the IEB function and/or morphology occur in PD. Colonic biopsies were performed in 31 PD patients and 11 age-matched healthy controls. The para- and transcellular permeability were evaluated by measuring sulfonic acid and horseradish peroxidase flux respectively, in colonic biopsies mounted in Ussing chambers. The expression and localization of the two tight junctions proteins ZO-1 and occludin were analyzed by Western blot and immunofluorescence, respectively. The para- and transcellular permeability were not different between PD patients and controls. The expression of occludin, but not ZO-1, was significantly lower in colonic samples from PD patients as compared to controls and the cellular distribution of both proteins was altered in colonic mucosal specimens from PD patients. Our findings provide evidence that the IEB is morphologically altered in PD and further reinforce the potential role of the gastrointestinal tract in the initiation and/or the progression of the disease.

No MeSH data available.


Related in: MedlinePlus