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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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Simple WIRS (acute stress) upregulates Sgk1 predominantly in the fiber tracts via HPA axis activation.(A, B) In situ hybridization images of Sgk1 mRNA. Dark-field photomicrographs showing the distribution of Sgk1 mRNA-expressing cells in the mouse brain on the sagittal (A) and frontal (B) planes. Sections were hybridized with a 35S-labeled antisense RNA probe for Sgk1 mRNA. As controls, adjacent sections were hybridized with 35S-labeled sense RNA probe (inset in a). Scale bar = 5 mm. (B) Simple exposure to WIRS increased Sgk1 mRNA expression in the mouse brain. cc, corpus callosum; ac, anterior commissure. Scale bar = 2 mm. (C) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Time-course dependent changes of Sgk1 mRNA levels in the corpus callosum analyzed after simple exposure to WIRS. *p<0.05, t-test. (D) Time-course dependent change of plasma corticosterone levels analyzed by the EIA kit after simple exposure to WIRS. *p<0.05, t-test. (E) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Intraperitoneal administration of 3 mg/kg DEX induced Sgk1 mRNA expression in the corpus callosum. *p<0.05, t-test. (F) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Adrenorectomy completely inhibited the upregulation of Sgk1 mRNA after simple exposure to WIRS (compare black bars). *p<0.05, t-test.
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pone-0019859-g001: Simple WIRS (acute stress) upregulates Sgk1 predominantly in the fiber tracts via HPA axis activation.(A, B) In situ hybridization images of Sgk1 mRNA. Dark-field photomicrographs showing the distribution of Sgk1 mRNA-expressing cells in the mouse brain on the sagittal (A) and frontal (B) planes. Sections were hybridized with a 35S-labeled antisense RNA probe for Sgk1 mRNA. As controls, adjacent sections were hybridized with 35S-labeled sense RNA probe (inset in a). Scale bar = 5 mm. (B) Simple exposure to WIRS increased Sgk1 mRNA expression in the mouse brain. cc, corpus callosum; ac, anterior commissure. Scale bar = 2 mm. (C) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Time-course dependent changes of Sgk1 mRNA levels in the corpus callosum analyzed after simple exposure to WIRS. *p<0.05, t-test. (D) Time-course dependent change of plasma corticosterone levels analyzed by the EIA kit after simple exposure to WIRS. *p<0.05, t-test. (E) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Intraperitoneal administration of 3 mg/kg DEX induced Sgk1 mRNA expression in the corpus callosum. *p<0.05, t-test. (F) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Adrenorectomy completely inhibited the upregulation of Sgk1 mRNA after simple exposure to WIRS (compare black bars). *p<0.05, t-test.

Mentions: In situ hybridization histochemistry for Sgk1 mRNA in the brains of normal adult mice shows that two types of cells express Sgk1 mRNA: those preferentially localized in the fiber tracts (oligodendrocytes) such as the corpus callosum and anterior commissure and the neurons that are localized in the CA3 region of the hippocampal formation (Figure 1A). Both in situ hybridization histochemistry and real-time polymerase chain reaction (PCR) for Sgk1 mRNA detection reveal that Sgk1 mRNA expression increased markedly in the corpus callosum and the anterior commissure, peaking 2 h following acute stress, and subsequently decreasing to control levels at 24 h (Figure 1B, 1C). However, Sgk1 transcription in neurons was not affected by acute stress (Figure S1).


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)

Simple WIRS (acute stress) upregulates Sgk1 predominantly in the fiber tracts via HPA axis activation.(A, B) In situ hybridization images of Sgk1 mRNA. Dark-field photomicrographs showing the distribution of Sgk1 mRNA-expressing cells in the mouse brain on the sagittal (A) and frontal (B) planes. Sections were hybridized with a 35S-labeled antisense RNA probe for Sgk1 mRNA. As controls, adjacent sections were hybridized with 35S-labeled sense RNA probe (inset in a). Scale bar = 5 mm. (B) Simple exposure to WIRS increased Sgk1 mRNA expression in the mouse brain. cc, corpus callosum; ac, anterior commissure. Scale bar = 2 mm. (C) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Time-course dependent changes of Sgk1 mRNA levels in the corpus callosum analyzed after simple exposure to WIRS. *p<0.05, t-test. (D) Time-course dependent change of plasma corticosterone levels analyzed by the EIA kit after simple exposure to WIRS. *p<0.05, t-test. (E) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Intraperitoneal administration of 3 mg/kg DEX induced Sgk1 mRNA expression in the corpus callosum. *p<0.05, t-test. (F) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Adrenorectomy completely inhibited the upregulation of Sgk1 mRNA after simple exposure to WIRS (compare black bars). *p<0.05, t-test.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3104997&req=5

pone-0019859-g001: Simple WIRS (acute stress) upregulates Sgk1 predominantly in the fiber tracts via HPA axis activation.(A, B) In situ hybridization images of Sgk1 mRNA. Dark-field photomicrographs showing the distribution of Sgk1 mRNA-expressing cells in the mouse brain on the sagittal (A) and frontal (B) planes. Sections were hybridized with a 35S-labeled antisense RNA probe for Sgk1 mRNA. As controls, adjacent sections were hybridized with 35S-labeled sense RNA probe (inset in a). Scale bar = 5 mm. (B) Simple exposure to WIRS increased Sgk1 mRNA expression in the mouse brain. cc, corpus callosum; ac, anterior commissure. Scale bar = 2 mm. (C) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Time-course dependent changes of Sgk1 mRNA levels in the corpus callosum analyzed after simple exposure to WIRS. *p<0.05, t-test. (D) Time-course dependent change of plasma corticosterone levels analyzed by the EIA kit after simple exposure to WIRS. *p<0.05, t-test. (E) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Intraperitoneal administration of 3 mg/kg DEX induced Sgk1 mRNA expression in the corpus callosum. *p<0.05, t-test. (F) Relative mRNA expression levels were determined by real-time PCR and normalized to that of GAPDH mRNA. Adrenorectomy completely inhibited the upregulation of Sgk1 mRNA after simple exposure to WIRS (compare black bars). *p<0.05, t-test.
Mentions: In situ hybridization histochemistry for Sgk1 mRNA in the brains of normal adult mice shows that two types of cells express Sgk1 mRNA: those preferentially localized in the fiber tracts (oligodendrocytes) such as the corpus callosum and anterior commissure and the neurons that are localized in the CA3 region of the hippocampal formation (Figure 1A). Both in situ hybridization histochemistry and real-time polymerase chain reaction (PCR) for Sgk1 mRNA detection reveal that Sgk1 mRNA expression increased markedly in the corpus callosum and the anterior commissure, peaking 2 h following acute stress, and subsequently decreasing to control levels at 24 h (Figure 1B, 1C). However, Sgk1 transcription in neurons was not affected by acute stress (Figure S1).

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