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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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Characterization of model mice exposed to repeated WIRS (chronic stress).(A, B) Effects of repeated WIRS as chronic stress on mouse behavior. Stressed mice exhibited significantly increased depression-like behavior compared with control mice in tail-suspension (A) and forced-swimming (B) tests. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test. (C) Less adult neural stem cells labeled by BrdU were found in the subgranular zone of the dentate gyrus (DG) in the stressed mice (C, Stress) than in the control mice (C, Cont). BrdU (75 mg/kg) was injected 4 times at 6-h intervals. Scale bars = 500 µm. (D) Quantification of the results shown in C. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test. (E) Alternation of plasma corticosterone 24 h after repeated WIRS. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test.
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pone-0019859-g002: Characterization of model mice exposed to repeated WIRS (chronic stress).(A, B) Effects of repeated WIRS as chronic stress on mouse behavior. Stressed mice exhibited significantly increased depression-like behavior compared with control mice in tail-suspension (A) and forced-swimming (B) tests. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test. (C) Less adult neural stem cells labeled by BrdU were found in the subgranular zone of the dentate gyrus (DG) in the stressed mice (C, Stress) than in the control mice (C, Cont). BrdU (75 mg/kg) was injected 4 times at 6-h intervals. Scale bars = 500 µm. (D) Quantification of the results shown in C. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test. (E) Alternation of plasma corticosterone 24 h after repeated WIRS. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test.

Mentions: To evaluate the depressive behavior of chronically stressed mice, immobility time was recorded in tail suspension tests during the last 6 min of a 10-min test period. The mice exposed to repeated WIRS (chronic stress) showed significant longer immobility times than control mice, indicating increased despair (Figure 2A). The immobility time recorded in the forced-swimming test was longer in the mice exposed to repeated WIRS (chronic stress) than in the control mice (Figure 2B). In addition, exposing mice to repeated stress resulted in a significant decrease in the number of neural stem cells of the adult hippocampus that took up BrdU (Figure 2C, 2D). Thus, this suggests that chronic stress inhibits neurogenesis in the hippocampus. Furthermore, repeated exposure to WIRS also upregulated of plasma corticosterone levels (Figure 2E).


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)

Characterization of model mice exposed to repeated WIRS (chronic stress).(A, B) Effects of repeated WIRS as chronic stress on mouse behavior. Stressed mice exhibited significantly increased depression-like behavior compared with control mice in tail-suspension (A) and forced-swimming (B) tests. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test. (C) Less adult neural stem cells labeled by BrdU were found in the subgranular zone of the dentate gyrus (DG) in the stressed mice (C, Stress) than in the control mice (C, Cont). BrdU (75 mg/kg) was injected 4 times at 6-h intervals. Scale bars = 500 µm. (D) Quantification of the results shown in C. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test. (E) Alternation of plasma corticosterone 24 h after repeated WIRS. The results are expressed as the mean ± SEM of three independent experiments. *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-g002: Characterization of model mice exposed to repeated WIRS (chronic stress).(A, B) Effects of repeated WIRS as chronic stress on mouse behavior. Stressed mice exhibited significantly increased depression-like behavior compared with control mice in tail-suspension (A) and forced-swimming (B) tests. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test. (C) Less adult neural stem cells labeled by BrdU were found in the subgranular zone of the dentate gyrus (DG) in the stressed mice (C, Stress) than in the control mice (C, Cont). BrdU (75 mg/kg) was injected 4 times at 6-h intervals. Scale bars = 500 µm. (D) Quantification of the results shown in C. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test. (E) Alternation of plasma corticosterone 24 h after repeated WIRS. The results are expressed as the mean ± SEM of three independent experiments. *p<0.05, t-test.
Mentions: To evaluate the depressive behavior of chronically stressed mice, immobility time was recorded in tail suspension tests during the last 6 min of a 10-min test period. The mice exposed to repeated WIRS (chronic stress) showed significant longer immobility times than control mice, indicating increased despair (Figure 2A). The immobility time recorded in the forced-swimming test was longer in the mice exposed to repeated WIRS (chronic stress) than in the control mice (Figure 2B). In addition, exposing mice to repeated stress resulted in a significant decrease in the number of neural stem cells of the adult hippocampus that took up BrdU (Figure 2C, 2D). Thus, this suggests that chronic stress inhibits neurogenesis in the hippocampus. Furthermore, repeated exposure to WIRS also upregulated of plasma corticosterone levels (Figure 2E).

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