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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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Activation of the PDKI-SGKI-NDRG1-adhesion molecule pathway returns to the control level after 3 weeks recovery.(A) Representative transverse electron micrographs of the corpus callosum of no-stress controls (18-week-old mice) (Cont) and after 3 weeks recovery after exposure to WIRS (18-week-old mice) (stress & recover). Scale bars = 10 µm. (B) Quantification of the sum of the cross-sectional areas of the oligodendrocytes is shown in panel A. Morphometric measurements were made using ImageJ software. The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test. (C) Western blot analysis of the corpora callosa of mice exposed to repeated WIRS (15-week-old mice) and after 3 weeks recovery (18-week-old mice). In the lysates from the corpora callosa of the mice in which repeated exposure to WIRS was discontinued, no increase in PDK1 phosphorylation, SGK1 expression or phosphorylation, or the expression of adhesion molecules such as β-catenin was identified. (D) Effects of a chronic stress, i.e., 3-week recovery after exposure to repeated WIRS, on mouse behavior. Mice in which repeated exposure to WIRS (18-week-old mice) was discontinued show no significant difference in the tail-suspension test compared to the control mice (18-week-old mice). The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test.
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pone-0019859-g009: Activation of the PDKI-SGKI-NDRG1-adhesion molecule pathway returns to the control level after 3 weeks recovery.(A) Representative transverse electron micrographs of the corpus callosum of no-stress controls (18-week-old mice) (Cont) and after 3 weeks recovery after exposure to WIRS (18-week-old mice) (stress & recover). Scale bars = 10 µm. (B) Quantification of the sum of the cross-sectional areas of the oligodendrocytes is shown in panel A. Morphometric measurements were made using ImageJ software. The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test. (C) Western blot analysis of the corpora callosa of mice exposed to repeated WIRS (15-week-old mice) and after 3 weeks recovery (18-week-old mice). In the lysates from the corpora callosa of the mice in which repeated exposure to WIRS was discontinued, no increase in PDK1 phosphorylation, SGK1 expression or phosphorylation, or the expression of adhesion molecules such as β-catenin was identified. (D) Effects of a chronic stress, i.e., 3-week recovery after exposure to repeated WIRS, on mouse behavior. Mice in which repeated exposure to WIRS (18-week-old mice) was discontinued show no significant difference in the tail-suspension test compared to the control mice (18-week-old mice). The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test.

Mentions: Finally, it should be noted that the increase in the immobility time and interfibral space in the corpus callosum following repeated exposure to WIRS returned to control levels after interrupting exposure to WIRS for 3 weeks (Figure 9A, B, and D). Furthermore, the activation of the PDK1–SGK1–NDRG1–adhesion molecules pathway following repeated exposure to WIRS did not differ between groups following repeated exposure to WIRS (chronic stress) (S) and control mice (C) after interrupting exposure to WIRS for 3 weeks (Figure 9C, 18 w mice).


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)

Activation of the PDKI-SGKI-NDRG1-adhesion molecule pathway returns to the control level after 3 weeks recovery.(A) Representative transverse electron micrographs of the corpus callosum of no-stress controls (18-week-old mice) (Cont) and after 3 weeks recovery after exposure to WIRS (18-week-old mice) (stress & recover). Scale bars = 10 µm. (B) Quantification of the sum of the cross-sectional areas of the oligodendrocytes is shown in panel A. Morphometric measurements were made using ImageJ software. The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test. (C) Western blot analysis of the corpora callosa of mice exposed to repeated WIRS (15-week-old mice) and after 3 weeks recovery (18-week-old mice). In the lysates from the corpora callosa of the mice in which repeated exposure to WIRS was discontinued, no increase in PDK1 phosphorylation, SGK1 expression or phosphorylation, or the expression of adhesion molecules such as β-catenin was identified. (D) Effects of a chronic stress, i.e., 3-week recovery after exposure to repeated WIRS, on mouse behavior. Mice in which repeated exposure to WIRS (18-week-old mice) was discontinued show no significant difference in the tail-suspension test compared to the control mice (18-week-old mice). The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test.
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Related In: Results  -  Collection

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pone-0019859-g009: Activation of the PDKI-SGKI-NDRG1-adhesion molecule pathway returns to the control level after 3 weeks recovery.(A) Representative transverse electron micrographs of the corpus callosum of no-stress controls (18-week-old mice) (Cont) and after 3 weeks recovery after exposure to WIRS (18-week-old mice) (stress & recover). Scale bars = 10 µm. (B) Quantification of the sum of the cross-sectional areas of the oligodendrocytes is shown in panel A. Morphometric measurements were made using ImageJ software. The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test. (C) Western blot analysis of the corpora callosa of mice exposed to repeated WIRS (15-week-old mice) and after 3 weeks recovery (18-week-old mice). In the lysates from the corpora callosa of the mice in which repeated exposure to WIRS was discontinued, no increase in PDK1 phosphorylation, SGK1 expression or phosphorylation, or the expression of adhesion molecules such as β-catenin was identified. (D) Effects of a chronic stress, i.e., 3-week recovery after exposure to repeated WIRS, on mouse behavior. Mice in which repeated exposure to WIRS (18-week-old mice) was discontinued show no significant difference in the tail-suspension test compared to the control mice (18-week-old mice). The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test.
Mentions: Finally, it should be noted that the increase in the immobility time and interfibral space in the corpus callosum following repeated exposure to WIRS returned to control levels after interrupting exposure to WIRS for 3 weeks (Figure 9A, B, and D). Furthermore, the activation of the PDK1–SGK1–NDRG1–adhesion molecules pathway following repeated exposure to WIRS did not differ between groups following repeated exposure to WIRS (chronic stress) (S) and control mice (C) after interrupting exposure to WIRS for 3 weeks (Figure 9C, 18 w mice).

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