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Altered expression of claudin family proteins in Alzheimer's disease and vascular dementia brains.

Romanitan MO, Popescu BO, Spulber S, Băjenaru O, Popescu LM, Winblad B, Bogdanovic N - J. Cell. Mol. Med. (2010)

Bottom Line: We report a significant increase in ratio of neurons expressing Cl-2, Cl-5 and Cl-11 in both AD and VaD as compared to aged controls.The ratio of astrocytes expressing Cl-2 and Cl-11 was significantly higher in AD and VaD as compared to aged controls.The ratio of oligodendrocytes expressing Cl-11 was significantly higher in AD and the ratio of oligodendrocytes expressing Cl-2 was significantly higher in VaD as compared to aged controls.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Medicine, 'Victor Babeş' National Institute of Pathology, Spl Independenţei, Bucharest, Romania.

ABSTRACT
Claudins (Cls) are a multigene family of transmembrane proteins with different tissue distribution, which have an essential role in the formation and sealing capacity of tight junctions (TJs). At the level of the blood-brain barrier (BBB), TJs are the main molecular structures which separate the neuronal milieu from the circulatory space, by a restriction of the paracellular flow of water, ions and larger molecules into the brain. Different studies suggested recently significant BBB alterations in both vascular and degenerative dementia types. In a previous study we found in Alzheimer's disease (AD) and vascular dementia (VaD) brains an altered expression of occludin, a molecular partner of Cls in the TJs structure. Therefore in this study, using an immunohistochemical approach, we investigated the expression of Cl family proteins (Cl-2, Cl-5 and Cl-11) in frontal cortex of aged control, AD and VaD brains. To estimate the number of Cl-expressing cells, we applied a random systematic sampling and the unbiased optical fractionator method. We found selected neurons, astrocytes, oligodendrocytes and endothelial cells expressing Cl-2, Cl-5 and Cl-11 at detectable levels in all cases studied. We report a significant increase in ratio of neurons expressing Cl-2, Cl-5 and Cl-11 in both AD and VaD as compared to aged controls. The ratio of astrocytes expressing Cl-2 and Cl-11 was significantly higher in AD and VaD as compared to aged controls. The ratio of oligodendrocytes expressing Cl-11 was significantly higher in AD and the ratio of oligodendrocytes expressing Cl-2 was significantly higher in VaD as compared to aged controls. Within the cerebral cortex, Cls were selectively expressed by pyramidal neurons, which are the ones responsible for cognitive processes and affected by AD pathology. Our findings suggest a new function of Cl family proteins which might be linked to response to cellular stress.

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Ratios of Cl-2, Cl-5 and Cl-11-expressing cells in control, AD and VaD brains, in the frontal cortex, Brodmann area 46/9. The neuronal, astrocyte or oligodendrocyte ratio was defined as (number of Cl-expressing cells / total number of cells) × 100. To compare the cell ratio between controls, AD and VaD (two by two) factorial ANOVA has been used, followed by the Fisher’s LSD post hoc test. Error bars mark the S.D.
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fig02: Ratios of Cl-2, Cl-5 and Cl-11-expressing cells in control, AD and VaD brains, in the frontal cortex, Brodmann area 46/9. The neuronal, astrocyte or oligodendrocyte ratio was defined as (number of Cl-expressing cells / total number of cells) × 100. To compare the cell ratio between controls, AD and VaD (two by two) factorial ANOVA has been used, followed by the Fisher’s LSD post hoc test. Error bars mark the S.D.

Mentions: Subsequently, we used a quantitative approach in order to estimate the number of Cl-expressing neurons in control, AD and VaD groups. Table 2 presents comparatively the quantitative data of neurons/mm2 and Cl-2, Cl-5 and Cl-11+ neurons/mm2 in control, AD and VaD groups, respectively. The number of neurons did not significantly differ between the groups analysed. The area chosen for counting was similar in all cases (with around 100 counting frames/area) and there was no significant difference in the density (number of neurons/area) between the cases analysed. Qualitatively, we found no areas with marked heterogeneity in distribution of Cls. The ratios of Cl-2, Cl-5 and Cl-11-expressing neurons were significantly higher in the AD group (54.02 ± 1.77, P < 0.05, 39.82 ± 3.75, P < 0.05 and 71.62 ± 9.19, P < 0.05, respectively) and in the VaD group (38.07 ± 6.97, P < 0.05, 26.56 ± 4.44, P < 0.05 and 68.34 ± 7.19, P < 0.05, respectively) as compared to the control group (7.30 ± 1.36, 9.62 ± 13.08 and 23.77 ± 5.00, respectively), as shown in Fig. 2. The ratio of Cl-2-expressing neurons was significantly higher in the AD group as compared to the VaD group (P < 0.05). The ratios of Cl-5 and Cl-11-expressing neurons did not differ significantly between AD and VaD groups.


Altered expression of claudin family proteins in Alzheimer's disease and vascular dementia brains.

Romanitan MO, Popescu BO, Spulber S, Băjenaru O, Popescu LM, Winblad B, Bogdanovic N - J. Cell. Mol. Med. (2010)

Ratios of Cl-2, Cl-5 and Cl-11-expressing cells in control, AD and VaD brains, in the frontal cortex, Brodmann area 46/9. The neuronal, astrocyte or oligodendrocyte ratio was defined as (number of Cl-expressing cells / total number of cells) × 100. To compare the cell ratio between controls, AD and VaD (two by two) factorial ANOVA has been used, followed by the Fisher’s LSD post hoc test. Error bars mark the S.D.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822746&req=5

fig02: Ratios of Cl-2, Cl-5 and Cl-11-expressing cells in control, AD and VaD brains, in the frontal cortex, Brodmann area 46/9. The neuronal, astrocyte or oligodendrocyte ratio was defined as (number of Cl-expressing cells / total number of cells) × 100. To compare the cell ratio between controls, AD and VaD (two by two) factorial ANOVA has been used, followed by the Fisher’s LSD post hoc test. Error bars mark the S.D.
Mentions: Subsequently, we used a quantitative approach in order to estimate the number of Cl-expressing neurons in control, AD and VaD groups. Table 2 presents comparatively the quantitative data of neurons/mm2 and Cl-2, Cl-5 and Cl-11+ neurons/mm2 in control, AD and VaD groups, respectively. The number of neurons did not significantly differ between the groups analysed. The area chosen for counting was similar in all cases (with around 100 counting frames/area) and there was no significant difference in the density (number of neurons/area) between the cases analysed. Qualitatively, we found no areas with marked heterogeneity in distribution of Cls. The ratios of Cl-2, Cl-5 and Cl-11-expressing neurons were significantly higher in the AD group (54.02 ± 1.77, P < 0.05, 39.82 ± 3.75, P < 0.05 and 71.62 ± 9.19, P < 0.05, respectively) and in the VaD group (38.07 ± 6.97, P < 0.05, 26.56 ± 4.44, P < 0.05 and 68.34 ± 7.19, P < 0.05, respectively) as compared to the control group (7.30 ± 1.36, 9.62 ± 13.08 and 23.77 ± 5.00, respectively), as shown in Fig. 2. The ratio of Cl-2-expressing neurons was significantly higher in the AD group as compared to the VaD group (P < 0.05). The ratios of Cl-5 and Cl-11-expressing neurons did not differ significantly between AD and VaD groups.

Bottom Line: We report a significant increase in ratio of neurons expressing Cl-2, Cl-5 and Cl-11 in both AD and VaD as compared to aged controls.The ratio of astrocytes expressing Cl-2 and Cl-11 was significantly higher in AD and VaD as compared to aged controls.The ratio of oligodendrocytes expressing Cl-11 was significantly higher in AD and the ratio of oligodendrocytes expressing Cl-2 was significantly higher in VaD as compared to aged controls.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Medicine, 'Victor Babeş' National Institute of Pathology, Spl Independenţei, Bucharest, Romania.

ABSTRACT
Claudins (Cls) are a multigene family of transmembrane proteins with different tissue distribution, which have an essential role in the formation and sealing capacity of tight junctions (TJs). At the level of the blood-brain barrier (BBB), TJs are the main molecular structures which separate the neuronal milieu from the circulatory space, by a restriction of the paracellular flow of water, ions and larger molecules into the brain. Different studies suggested recently significant BBB alterations in both vascular and degenerative dementia types. In a previous study we found in Alzheimer's disease (AD) and vascular dementia (VaD) brains an altered expression of occludin, a molecular partner of Cls in the TJs structure. Therefore in this study, using an immunohistochemical approach, we investigated the expression of Cl family proteins (Cl-2, Cl-5 and Cl-11) in frontal cortex of aged control, AD and VaD brains. To estimate the number of Cl-expressing cells, we applied a random systematic sampling and the unbiased optical fractionator method. We found selected neurons, astrocytes, oligodendrocytes and endothelial cells expressing Cl-2, Cl-5 and Cl-11 at detectable levels in all cases studied. We report a significant increase in ratio of neurons expressing Cl-2, Cl-5 and Cl-11 in both AD and VaD as compared to aged controls. The ratio of astrocytes expressing Cl-2 and Cl-11 was significantly higher in AD and VaD as compared to aged controls. The ratio of oligodendrocytes expressing Cl-11 was significantly higher in AD and the ratio of oligodendrocytes expressing Cl-2 was significantly higher in VaD as compared to aged controls. Within the cerebral cortex, Cls were selectively expressed by pyramidal neurons, which are the ones responsible for cognitive processes and affected by AD pathology. Our findings suggest a new function of Cl family proteins which might be linked to response to cellular stress.

Show MeSH
Related in: MedlinePlus