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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 SGK1-NDRG1 pathway also causes morphological changes in primary cultured oligodendrocytes.(A, C, E) Morphology of primary cultured oligodendrocytes treated with (+DEX) (a, right column) or without DEX (-DEX) for 2 days (A, left column). Overexpression of the active form of SGK1 (SGK1-S422D) (C, right column) and overexpression of phosphorylated NDRG1 (NDRG1-S330D) (E, right column) by using the ImageJ tracing tool. As controls for the last 2 experiments, the effects of the overexpression of SGK1-S422A (the inactive form of SGK1) (C, left column) and NDRG1-S330A (the non-phosphorylated form of NDRG1) (E, left column) were examined. NG2 and MBP were used as markers of immature and mature oligodendrocytes, respectively. (B, D, F) Quantification of oligodendrocyte size (diameters) is shown in panels A, C, and E, respectively. Morphometric measurements of oligodendrocyte diameters were performed using ImageJ software. The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test.
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pone-0019859-g008: Activation of the SGK1-NDRG1 pathway also causes morphological changes in primary cultured oligodendrocytes.(A, C, E) Morphology of primary cultured oligodendrocytes treated with (+DEX) (a, right column) or without DEX (-DEX) for 2 days (A, left column). Overexpression of the active form of SGK1 (SGK1-S422D) (C, right column) and overexpression of phosphorylated NDRG1 (NDRG1-S330D) (E, right column) by using the ImageJ tracing tool. As controls for the last 2 experiments, the effects of the overexpression of SGK1-S422A (the inactive form of SGK1) (C, left column) and NDRG1-S330A (the non-phosphorylated form of NDRG1) (E, left column) were examined. NG2 and MBP were used as markers of immature and mature oligodendrocytes, respectively. (B, D, F) Quantification of oligodendrocyte size (diameters) is shown in panels A, C, and E, respectively. Morphometric measurements of oligodendrocyte diameters were performed using ImageJ software. The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test.

Mentions: The addition of DEX resulted in an approximately 1.5-fold increase in the diameter of the oligodendrocytes labeled by MBP, compared to the untreated oligodendrocytes (control) (Figure 8A, B). Overexpression of the active forms of SGK1 (SGK1-S422D) and NRDG1 (NDRG1-S330D) in the oligodendrocytes had the same effect as repeated exposure to WIRS. Overexpression of the inactive forms of SGK1 (SGK1-S422A) and NDRG1 (NDRG1-S330A) did not induce morphological changes in oligodendrocytes, while overexpression of SGK1-S422D and NDRG1-S330D increased the diameter of the oligodendrocytes (1.38- and 1.39-fold increases for SGK1 and NDRG1, respectively) (Figure 8C–F).


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 SGK1-NDRG1 pathway also causes morphological changes in primary cultured oligodendrocytes.(A, C, E) Morphology of primary cultured oligodendrocytes treated with (+DEX) (a, right column) or without DEX (-DEX) for 2 days (A, left column). Overexpression of the active form of SGK1 (SGK1-S422D) (C, right column) and overexpression of phosphorylated NDRG1 (NDRG1-S330D) (E, right column) by using the ImageJ tracing tool. As controls for the last 2 experiments, the effects of the overexpression of SGK1-S422A (the inactive form of SGK1) (C, left column) and NDRG1-S330A (the non-phosphorylated form of NDRG1) (E, left column) were examined. NG2 and MBP were used as markers of immature and mature oligodendrocytes, respectively. (B, D, F) Quantification of oligodendrocyte size (diameters) is shown in panels A, C, and E, respectively. Morphometric measurements of oligodendrocyte diameters were performed using ImageJ software. The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3104997&req=5

pone-0019859-g008: Activation of the SGK1-NDRG1 pathway also causes morphological changes in primary cultured oligodendrocytes.(A, C, E) Morphology of primary cultured oligodendrocytes treated with (+DEX) (a, right column) or without DEX (-DEX) for 2 days (A, left column). Overexpression of the active form of SGK1 (SGK1-S422D) (C, right column) and overexpression of phosphorylated NDRG1 (NDRG1-S330D) (E, right column) by using the ImageJ tracing tool. As controls for the last 2 experiments, the effects of the overexpression of SGK1-S422A (the inactive form of SGK1) (C, left column) and NDRG1-S330A (the non-phosphorylated form of NDRG1) (E, left column) were examined. NG2 and MBP were used as markers of immature and mature oligodendrocytes, respectively. (B, D, F) Quantification of oligodendrocyte size (diameters) is shown in panels A, C, and E, respectively. Morphometric measurements of oligodendrocyte diameters were performed using ImageJ software. The results are expressed as the mean ± SEM of 3 independent experiments. *p<0.05, t-test.
Mentions: The addition of DEX resulted in an approximately 1.5-fold increase in the diameter of the oligodendrocytes labeled by MBP, compared to the untreated oligodendrocytes (control) (Figure 8A, B). Overexpression of the active forms of SGK1 (SGK1-S422D) and NRDG1 (NDRG1-S330D) in the oligodendrocytes had the same effect as repeated exposure to WIRS. Overexpression of the inactive forms of SGK1 (SGK1-S422A) and NDRG1 (NDRG1-S330A) did not induce morphological changes in oligodendrocytes, while overexpression of SGK1-S422D and NDRG1-S330D increased the diameter of the oligodendrocytes (1.38- and 1.39-fold increases for SGK1 and NDRG1, respectively) (Figure 8C–F).

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