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Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum.

Miyata S, Koyama Y, Takemoto K, Yoshikawa K, Ishikawa T, Taniguchi M, Inoue K, Aoki M, Hori O, Katayama T, Tohyama M - PLoS ONE (2011)

Bottom Line: Further, stress activates the hypothalamic-pituitary-adrenocortical (HPA) system by elevating plasma cortisol levels.However, little is known about the related downstream molecular pathway.Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. smiyata@anat2.med.osaka-u.ac.jp

ABSTRACT
Repeated stressful events are known to be associated with onset of depression. Further, stress activates the hypothalamic-pituitary-adrenocortical (HPA) system by elevating plasma cortisol levels. However, little is known about the related downstream molecular pathway. In this study, by using repeated water-immersion and restraint stress (WIRS) as a stressor for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to WIRS activates the 3-phosphoinositide-dependent protein kinase (PDK1)-serum glucocorticoid regulated kinase (SGK1)-N-myc downstream-regulated gene 1 (NDRG1)-adhesion molecule (i.e., N-cadherin, α-catenin, and β-catenin) stabilization pathway via an increase in plasma corticosterone levels; (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes; and (3) after recovery from chronic stress, the abnormal arborization of oligodendrocytes and depression-like symptoms return to the control levels. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms.

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Repeated exposure to WIRS upregulates adhesion molecules expression levels in oligodendrocytes of the fiber tracts.(A) Immunoprecipitation and western blot analysis show that repeated exposure to WIRS elevated the interaction between NDRG1 and β-catenin (second panel), and that the expression levels of β-catenin, N-cadherin, and α-catenin were elevated in the corpus callosum. (B) Immunohistochemical analysis of β-catenin and N-cadherin in the corpus callosum demonstrates increased labeling of the processes of the oligodendrocytes (i.e., greater number and intensity) in mice exposed to repeated WIRS. Scale bar = 50 µm. (C, D) Immunocytochemical analysis of β-catenin and N-cadherin in SK-N-SH cells overexpressing non-phosphorylated (NDRG1-S330A) or phosphorylated NDRG1 (NDRG1-S330D). Increased expression of β-catenin (C) and N-cadherin (D) due to the overexpression of the phosphorylated form of NDRG1 (NDRG1-S330D) were mostly observed on the surfaces of the cell bodies and the processes of SK-N-SH cells. Scale bar = 20 µm. (E) Immunoprecipitation and western blot analysis show that overexpression of phosphorylated NDRG1 (NDRG1-S330D) upregulated the interaction between NDRG1 and β-catenin (second column), and that the expression levels of β-catenin, N-cadherin, and α-catenin were elevated in SK-N-SH cells. SK, no-transfection control (SK-N-SH cells).
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pone-0019859-g006: Repeated exposure to WIRS upregulates adhesion molecules expression levels in oligodendrocytes of the fiber tracts.(A) Immunoprecipitation and western blot analysis show that repeated exposure to WIRS elevated the interaction between NDRG1 and β-catenin (second panel), and that the expression levels of β-catenin, N-cadherin, and α-catenin were elevated in the corpus callosum. (B) Immunohistochemical analysis of β-catenin and N-cadherin in the corpus callosum demonstrates increased labeling of the processes of the oligodendrocytes (i.e., greater number and intensity) in mice exposed to repeated WIRS. Scale bar = 50 µm. (C, D) Immunocytochemical analysis of β-catenin and N-cadherin in SK-N-SH cells overexpressing non-phosphorylated (NDRG1-S330A) or phosphorylated NDRG1 (NDRG1-S330D). Increased expression of β-catenin (C) and N-cadherin (D) due to the overexpression of the phosphorylated form of NDRG1 (NDRG1-S330D) were mostly observed on the surfaces of the cell bodies and the processes of SK-N-SH cells. Scale bar = 20 µm. (E) Immunoprecipitation and western blot analysis show that overexpression of phosphorylated NDRG1 (NDRG1-S330D) upregulated the interaction between NDRG1 and β-catenin (second column), and that the expression levels of β-catenin, N-cadherin, and α-catenin were elevated in SK-N-SH cells. SK, no-transfection control (SK-N-SH cells).

Mentions: We found that the expression levels of the main adhesion molecules, such as N-cadherin, α-catenin, and β-catenin, which comprise adherens junctions, increased in the corpus callosum after repeated exposure to WIRS (Figure 6A). This result was confirmed by subsequent immunohistochemical analysis, indicating that these molecules are localized in the oligodendrocytes of the corpus callosum (Figure 6B). The processes of the oligodendrocytes labeled by these molecules and found in the corpus callosum after repeated exposure to WIRS were more numerous and thicker than those of the controls. Furthermore, these processes could be traced for longer distances than those of the controls (Figure 6B).


Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum.

Miyata S, Koyama Y, Takemoto K, Yoshikawa K, Ishikawa T, Taniguchi M, Inoue K, Aoki M, Hori O, Katayama T, Tohyama M - PLoS ONE (2011)

Repeated exposure to WIRS upregulates adhesion molecules expression levels in oligodendrocytes of the fiber tracts.(A) Immunoprecipitation and western blot analysis show that repeated exposure to WIRS elevated the interaction between NDRG1 and β-catenin (second panel), and that the expression levels of β-catenin, N-cadherin, and α-catenin were elevated in the corpus callosum. (B) Immunohistochemical analysis of β-catenin and N-cadherin in the corpus callosum demonstrates increased labeling of the processes of the oligodendrocytes (i.e., greater number and intensity) in mice exposed to repeated WIRS. Scale bar = 50 µm. (C, D) Immunocytochemical analysis of β-catenin and N-cadherin in SK-N-SH cells overexpressing non-phosphorylated (NDRG1-S330A) or phosphorylated NDRG1 (NDRG1-S330D). Increased expression of β-catenin (C) and N-cadherin (D) due to the overexpression of the phosphorylated form of NDRG1 (NDRG1-S330D) were mostly observed on the surfaces of the cell bodies and the processes of SK-N-SH cells. Scale bar = 20 µm. (E) Immunoprecipitation and western blot analysis show that overexpression of phosphorylated NDRG1 (NDRG1-S330D) upregulated the interaction between NDRG1 and β-catenin (second column), and that the expression levels of β-catenin, N-cadherin, and α-catenin were elevated in SK-N-SH cells. SK, no-transfection control (SK-N-SH cells).
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Related In: Results  -  Collection

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pone-0019859-g006: Repeated exposure to WIRS upregulates adhesion molecules expression levels in oligodendrocytes of the fiber tracts.(A) Immunoprecipitation and western blot analysis show that repeated exposure to WIRS elevated the interaction between NDRG1 and β-catenin (second panel), and that the expression levels of β-catenin, N-cadherin, and α-catenin were elevated in the corpus callosum. (B) Immunohistochemical analysis of β-catenin and N-cadherin in the corpus callosum demonstrates increased labeling of the processes of the oligodendrocytes (i.e., greater number and intensity) in mice exposed to repeated WIRS. Scale bar = 50 µm. (C, D) Immunocytochemical analysis of β-catenin and N-cadherin in SK-N-SH cells overexpressing non-phosphorylated (NDRG1-S330A) or phosphorylated NDRG1 (NDRG1-S330D). Increased expression of β-catenin (C) and N-cadherin (D) due to the overexpression of the phosphorylated form of NDRG1 (NDRG1-S330D) were mostly observed on the surfaces of the cell bodies and the processes of SK-N-SH cells. Scale bar = 20 µm. (E) Immunoprecipitation and western blot analysis show that overexpression of phosphorylated NDRG1 (NDRG1-S330D) upregulated the interaction between NDRG1 and β-catenin (second column), and that the expression levels of β-catenin, N-cadherin, and α-catenin were elevated in SK-N-SH cells. SK, no-transfection control (SK-N-SH cells).
Mentions: We found that the expression levels of the main adhesion molecules, such as N-cadherin, α-catenin, and β-catenin, which comprise adherens junctions, increased in the corpus callosum after repeated exposure to WIRS (Figure 6A). This result was confirmed by subsequent immunohistochemical analysis, indicating that these molecules are localized in the oligodendrocytes of the corpus callosum (Figure 6B). The processes of the oligodendrocytes labeled by these molecules and found in the corpus callosum after repeated exposure to WIRS were more numerous and thicker than those of the controls. Furthermore, these processes could be traced for longer distances than those of the controls (Figure 6B).

Bottom Line: Further, stress activates the hypothalamic-pituitary-adrenocortical (HPA) system by elevating plasma cortisol levels.However, little is known about the related downstream molecular pathway.Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. smiyata@anat2.med.osaka-u.ac.jp

ABSTRACT
Repeated stressful events are known to be associated with onset of depression. Further, stress activates the hypothalamic-pituitary-adrenocortical (HPA) system by elevating plasma cortisol levels. However, little is known about the related downstream molecular pathway. In this study, by using repeated water-immersion and restraint stress (WIRS) as a stressor for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to WIRS activates the 3-phosphoinositide-dependent protein kinase (PDK1)-serum glucocorticoid regulated kinase (SGK1)-N-myc downstream-regulated gene 1 (NDRG1)-adhesion molecule (i.e., N-cadherin, α-catenin, and β-catenin) stabilization pathway via an increase in plasma corticosterone levels; (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes; and (3) after recovery from chronic stress, the abnormal arborization of oligodendrocytes and depression-like symptoms return to the control levels. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms.

Show MeSH
Related in: MedlinePlus