Sgk1 regulates desmoglein 1 expression levels in oligodendrocytes in the mouse corpus callosum after chronic stress exposure

Miyata, Sumiko; Yoshikawa, Kohei; Taniguchi, Manabu; Ishikawa, Tomoyoshi; Tanaka, Takashi; Shimizu, Shoko; Tohyama, Masaya

doi:10.1016/j.bbrc.2015.05.109

Cited by 16 publications

(20 citation statements)

References 31 publications

(19 reference statements)

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“…20 In an experimental study, Dsg1 was found to be expressed in the corpus callosum of the mouse brain and was localized around the plasma membrane regions of oligodendrocytes. 21 The latter lends weight to an earlier study demonstrating that murine Dsg1-γ expression is not restricted to the skin, as it is also expressed in the brain, skeletal muscle, and liver, among other tissues. 22 In bullous pemphigoid, an obvious a s s o c i at i o n w it h n e u r o l o g i c c o n d it i o n s h a s b e e n established.…”

Section: Discussionmentioning

confidence: 62%

Association Between Pemphigus and Neurologic Diseases

et al. 2018

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IMPORTANCE The association between pemphigus and neurologic diseases was not evaluated systematically in the past. In a recent uncontrolled cross-sectional study, Parkinson disease was found to be significantly associated with pemphigus; in the same study, epilepsy had a nonsignificant association with pemphigus. Several case reports have suggested that pemphigus coexists with multiple sclerosis and dementia. OBJECTIVE To estimate the association between pemphigus and 4 neurologic conditions (dementia, epilepsy, Parkinson disease, and multiple sclerosis), using one of the largest cohorts of patients with pemphigus. DESIGN, SETTING, AND PARTICIPANTS A retrospective population-based cross-sectional study was performed between January 1, 2004, and December 31, 2014, using the database of Clalit Health Services, the largest public health care organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. A total of 1985 patients with a new diagnosis of pemphigus and 9874 controls were included in the study. MAIN OUTCOMES AND MEASURES The proportion of dementia, epilepsy, Parkinson disease, and multiple sclerosis was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control participants. Logistic regression was used to calculate odds ratios (ORs) for dementia, epilepsy, Parkinson disease, and multiple sclerosis. The association was examined after a sensitivity analysis that included only patients treated with long-term, pemphigus-specific medications (corticosteroids, immunosuppressants, or rituximab) and after adjustment for several confounding factors. RESULTS When comparing the 1985 cases (1188 women and 797 men; mean [SD] age, 72.1 [18.5] years) with the 9874 controls (5912 women and 3962 men; mean [SD] age, 72.1 [18.5] years), dementia was seen in 622 cases (31.3%) vs 1856 controls (18.8%), with an OR of 1.97 (95% CI, 1.77-2.20). Epilepsy was present in 74 cases (3.7%) vs 210 controls (2.1%), with an OR of 1.78 (95% CI, 1.36-2.33). Parkinson disease was seen in 175 cases (8.8%) vs 437 controls (4.4%), with an OR of 2.09 (95% CI, 1.74-2.51). Multiple sclerosis was present in 2 cases (0.1%) vs 6 controls (0.01%), with an OR of 1.65 (95% CI, 0.34-8.22). Study findings were robust to sensitivity analysis that included patients receiving pemphigus-specific treatments. Estimates were not altered significantly after controlling for comorbidities and overuse of health care. CONCLUSIONS AND RELEVANCE An association was observed between pemphigus and specific neurologic diseases, including dementia, Parkinson disease, and epilepsy. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid neurologic disorders and receive appropriate treatment.

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Section: Discussionmentioning

confidence: 62%

Association Between Pemphigus and Neurologic Diseases

et al. 2018

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“…Likewise, multiple differentially expressed genes in the PAG of SNI and CUS mice have been linked with anxiety and depression. The expression of Sgk1 , upregulated in both SNI and CUS mice, is upregulated in the corpus callosum (118), and hippocampus (119) by chronic stress, and mRNA amounts of Sgk1 are increased in peripheral blood samples from patients with major depression (119). Similarly, genetic deletion of Slc17a8 ( Vglut3 ), the expression of which was reduced in the PAG of both SNI and CUS groups in our study, enhances anxiety-like behaviors in adult mice that correspond with decreases in 5-HT 1A -mediated neurotransmission in the raphe nuclei (120).…”

Section: Discussionmentioning

confidence: 99%

Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression

et al. 2017

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Neuropathic pain is a complex chronic condition characterized by a wide range of sensory, cognitive, and affective symptoms. A large percentage of neuropathic pain patients are also afflicted with depression and anxiety disorders – a pattern that is reliably replicated in animal models. Furthermore, clinical and preclinical studies indicate that chronic pain corresponds with adaptations in several brain networks involved in mood, motivation, and reward. Chronic stress is also a major risk factor for depression. We investigated whether chronic pain and stress affect similar mechanisms, and whether chronic pain can affect gene expression patterns known to be involved in depression. Using two mouse models for neuropathic pain and depression (spared nerve injury (SNI) and chronic unpredictable stress (CUS)) we performed next generation RNA-sequencing and pathway analysis to monitor changes in gene expression in the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the periaqueductal grey (PAG). These three brain regions are implicated in the pathophysiology of depression and in the modulation of pain. In addition to finding unique transcriptome profiles across the three brain regions,.we identified a substantial number of signaling pathway-associated genes with similar changes in expression in both SNI and CUS mice. Many of these genes have been implicated in depression, anxiety and chronic pain in patients. Our study provides a resource of the changes in gene expression induced by long-term neuropathic pain in three distinct brain regions and reveals molecular connections between pain and chronic stress.

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“…In oligodendrocytes, SGK1 has been linked to a phospho-relay signaling pathway in which the protein is downstream from phosphatidylinositol 3-kinase (PI3K) and PI3K-3-phosphoinositide-dependent protein kinase (PDK1) and directly upstream of N-myc downstream-regulated gene 1 (NDRG1) [29]. Activation of NDRG1 subsequently leads to altered oligodendrocyte cell adhesion molecule expression and associated changes in cell morphology [4,29,32]. The regulation of Sgk1 expression in oligodendrocytes by acute psychological stress and time of day may be an important component of a dynamic experience-dependent interplay between oligodendrocytes and neuronal function including neuroplasticity.…”

Section: Discussionmentioning

confidence: 99%

Dynamic glucocorticoid-dependent regulation of Sgk1 expression in oligodendrocytes of adult male rat brain by acute stress and time of day

et al. 2017

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Recent studies support plasticity in adult brain white matter structure and myelination in response to various experiential factors. One possible contributor to this plasticity may be activity-dependent modulation of serum- and glucocorticoid-inducible kinase 1 (Sgk1) expression in oligodendrocytes. We examined whether Sgk1 expression in adult rat brain white matter is increased by acute stress-induced elevations in endogenous corticosterone and whether it fluctuates with diurnal variations in corticosterone. We observed rapid increases (within 30 min) in Sgk1 mRNA in the corpus callosum in response to acute stress, as well as large increases at the beginning of the rat’s active period (the time of peak corticosterone secretion). These increases were absent in adrenalectomized rats. Corticosterone treatment of adrenalectomized rats also rapidly increased corpus callosum Sgk1 mRNA. The majority of Sgk1 mRNA in corpus callosum was co-localized with myelin basic protein mRNA, suggesting that mature oligodendrocytes respond dynamically to acute stress and circadian rhythms. The regulation of Sgk1 expression by acute stress and time of day was selective for white matter, with limited alteration of Sgk1 expression by these factors in hippocampus and somatosensory cortex. These results indicate a unique sensitivity of oligodendrocyte Sgk1 expression to activity-dependent fluctuations in corticosterone hormone secretion, and raises the prospect that hypothalamic-pituitary-adrenal axis dysregulation or glucocorticoid pharmacotherapy may compromise the normal activity-dependent interactions between oligodendrocytes and neurons.

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Sgk1 regulates desmoglein 1 expression levels in oligodendrocytes in the mouse corpus callosum after chronic stress exposure

Cited by 16 publications

References 31 publications

Association Between Pemphigus and Neurologic Diseases

Association Between Pemphigus and Neurologic Diseases

Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression

Dynamic glucocorticoid-dependent regulation of Sgk1 expression in oligodendrocytes of adult male rat brain by acute stress and time of day

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