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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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Chronic stress upregulates Sgk1 predominantly in the fiber tracts via HPA axis activation.(A, B) In situ hybridization images of Sgk1 mRNA. Sgk1 mRNA expression in the corpus callosum (cc) and anterior commissure (ac) was elevated in mice after repeated exposed to WIRS (B) compared with the expression of Sgk1 mRNA in these bundles (A). Scale bar = 2 mm. (C, D) Enlargement of the squares in (A) and (B), respectively. Scale bar = 100 µm. (E, F) Merged images of Nissl staining and in situ hybridization images of Sgk1 mRNA. The distribution of cells expressing Sgk1 mRNA in the corpus callosum of the control (E) and repeated WIRS-exposed mice (F) in bright-filed photomicrographs. Positive grains were concentrated in the oligodendrocytes. Scale bars = 50 µm. (G) Western blot analysis shows that repeated WIRS decreases MBP expression in the corpus callosum compared to the control mice.
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pone-0019859-g004: Chronic stress upregulates Sgk1 predominantly in the fiber tracts via HPA axis activation.(A, B) In situ hybridization images of Sgk1 mRNA. Sgk1 mRNA expression in the corpus callosum (cc) and anterior commissure (ac) was elevated in mice after repeated exposed to WIRS (B) compared with the expression of Sgk1 mRNA in these bundles (A). Scale bar = 2 mm. (C, D) Enlargement of the squares in (A) and (B), respectively. Scale bar = 100 µm. (E, F) Merged images of Nissl staining and in situ hybridization images of Sgk1 mRNA. The distribution of cells expressing Sgk1 mRNA in the corpus callosum of the control (E) and repeated WIRS-exposed mice (F) in bright-filed photomicrographs. Positive grains were concentrated in the oligodendrocytes. Scale bars = 50 µm. (G) Western blot analysis shows that repeated WIRS decreases MBP expression in the corpus callosum compared to the control mice.

Mentions: The Sgk1 mRNA expression was markedly increased in the fiber tracts such as the corpus callosum and the anterior commissure after repeated exposure to WIRS (Figure 3A, B). Sgk1 mRNA was almost exclusively localized in oligodendrocytes (Figure 4A–F). In addition, Sgk1 mRNA upregulation in the fiber tracts after the mice were exposed to repeated WIRS was abolished after adrenolectomy (Figure 3C, D), indicating that elevated levels of corticosterone after exposure to repeated stress increase Sgk1 expression in the oligodendrocytes. Sgk1 mRNA and SGK1 protein upregulation in the fiber tracts such as the corpus callosum was also confirmed by quantitative real-time PCR (Figure 3E) and western blotting analysis (Figure 3F), respectively.


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)

Chronic stress upregulates Sgk1 predominantly in the fiber tracts via HPA axis activation.(A, B) In situ hybridization images of Sgk1 mRNA. Sgk1 mRNA expression in the corpus callosum (cc) and anterior commissure (ac) was elevated in mice after repeated exposed to WIRS (B) compared with the expression of Sgk1 mRNA in these bundles (A). Scale bar = 2 mm. (C, D) Enlargement of the squares in (A) and (B), respectively. Scale bar = 100 µm. (E, F) Merged images of Nissl staining and in situ hybridization images of Sgk1 mRNA. The distribution of cells expressing Sgk1 mRNA in the corpus callosum of the control (E) and repeated WIRS-exposed mice (F) in bright-filed photomicrographs. Positive grains were concentrated in the oligodendrocytes. Scale bars = 50 µm. (G) Western blot analysis shows that repeated WIRS decreases MBP expression in the corpus callosum compared to the control mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104997&req=5

pone-0019859-g004: Chronic stress upregulates Sgk1 predominantly in the fiber tracts via HPA axis activation.(A, B) In situ hybridization images of Sgk1 mRNA. Sgk1 mRNA expression in the corpus callosum (cc) and anterior commissure (ac) was elevated in mice after repeated exposed to WIRS (B) compared with the expression of Sgk1 mRNA in these bundles (A). Scale bar = 2 mm. (C, D) Enlargement of the squares in (A) and (B), respectively. Scale bar = 100 µm. (E, F) Merged images of Nissl staining and in situ hybridization images of Sgk1 mRNA. The distribution of cells expressing Sgk1 mRNA in the corpus callosum of the control (E) and repeated WIRS-exposed mice (F) in bright-filed photomicrographs. Positive grains were concentrated in the oligodendrocytes. Scale bars = 50 µm. (G) Western blot analysis shows that repeated WIRS decreases MBP expression in the corpus callosum compared to the control mice.
Mentions: The Sgk1 mRNA expression was markedly increased in the fiber tracts such as the corpus callosum and the anterior commissure after repeated exposure to WIRS (Figure 3A, B). Sgk1 mRNA was almost exclusively localized in oligodendrocytes (Figure 4A–F). In addition, Sgk1 mRNA upregulation in the fiber tracts after the mice were exposed to repeated WIRS was abolished after adrenolectomy (Figure 3C, D), indicating that elevated levels of corticosterone after exposure to repeated stress increase Sgk1 expression in the oligodendrocytes. Sgk1 mRNA and SGK1 protein upregulation in the fiber tracts such as the corpus callosum was also confirmed by quantitative real-time PCR (Figure 3E) and western blotting analysis (Figure 3F), respectively.

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