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Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum.

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.

SUBMITTER: Miyata S

PROVIDER: S-EPMC3104997 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum.

Miyata Shingo S Koyama Yoshihisa Y Takemoto Kana K Yoshikawa Keiko K Ishikawa Toshiko T Taniguchi Manabu M Inoue Kiyoshi K Aoki Miwa M Hori Osamu O Katayama Taiichi T Tohyama Masaya M

PloS one 20110531 5

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 effec ...[more]

PMID: 21655274

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Project description:The Corpus Callosum (CC) is an important structure that includes the majority of fibers connecting the two brain hemispheres. Several neurodegenerative diseases may alter CC size and morphology leading to its atrophy and malfunction which may play a role in the pathological manifestations found in these diseases. The purpose of the current study is to determine any possible changes in CC size in patients suffering from Alzheimer's disease. The Study also investigated the effect of acetylcholinesterase inhibitors (AChEIs) on the size of CC and its association with improvement in the Alzheimer disease severity scores. Midsagittal size of CC were recorded prospectively from 439 routine T1-weighted MRI brain images in normal individuals. The internal skull surface was measured to calculate CC/ internal skull surface ratio. Two groups of patients were studied: 300 (150 male / 150 female) were healthy subjects and 130 (55 males / 75 females) had Alzheimer disease. Out of the 130 Alzheimer disease pateints, 70 patients were treated with Donepezil or Rivastigmine or both. The size of the CC was measured based on T1-weighted MRI images after the treatment to investigate any possible improvement in CC size. The mean surface area of CC in controls was 6.53±1.105 cm2. There was no significant difference between males and females (P < 0.627), and CC/ internal skull surface ratio was 4.41±0.77%. Patients with mild or severe Alzheimer disease showed a significant reduction in CC size compared to healthy controls. Treating mild Alzheimer patients with either Donepezil or Rivastigmine exerts a comparable therapeutic effect in improving the CC size. There was more improvement in the size of CC in patients with severe Alzheimer disease by using combined therapy of Donepezil and Rivastigmine than using single a medication. we measured the mean size of the various portions of the corpus callosum in normal individuals and Alzheimer patients before and after taking Donepezil and Rivastigmine. Alzheimer patients have pronounced reduction in CC which is corrected after taking Donepezil and Rivastigmine leading to remarkable improvement in Alzheimer disease severity scores.

Project description:Background: The corpus callosum (CC) is the most prominent white matter connection for interhemispheric information transfer. It is implicated in a variety of cognitive functions, which tend to decline with age. The region-specific projections of the fiber bundles with microstructural heterogeneity of the CC are associated with cognitive functions and diseases. However, how the CC is associated with the information transfer within functional networks and the connectivity changes during aging remain unclear. Studying the CC topography helps to understand the functional specialization and age-related changes of CC subregions. Methods: Diffusion tractography was used to subdivide the CC into seven subregions from 1,086 healthy volunteers within a wide age range (21-90 years), based on the connections to the cortical parcellations of the functional networks. Quantitative diffusion indices and connection probability were calculated to study the microstructure differences and age-related changes in the CC subregions. Results: According to the population-based probabilistic topography of the CC, part of the default mode network (DMN) and limbic network (LN) projected fibers through the genu and rostrum; the frontoparietal network (FPN), ventral attention network (VA) and somatomotor networks (SM) were interconnected by the CC body; callosal fibers arising from the part of the default mode network (DMN), dorsal attention network (DA) and visual network (VIS) passed through the splenium. Anterior CC subregions interconnecting DMN, LN, FPN, VA, and SM showed lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) than posterior CC subregions interconnecting DA and VIS. All the CC subregions showed slightly increasing FA and decreasing MD, RD, and axial diffusivity (AD) at younger ages and opposite trends at older ages. Besides, the anterior CC subregions exhibited larger microstructural and connectivity changes compared with the posterior CC subregions during aging. Conclusion: This study revealed the callosal subregions related to functional networks and uncovered an overall "anterior-to-posterior" region-specific changing trend during aging, which provides a baseline to identify the presence and timing of callosal connection states.

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Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum.

Publications

Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum.

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