Effect of Dexamethasone on Glutamine Synthetase and Glial Fibrillary Acidic Protein; in Normal and Transformed Astrocytes

Weir, Mary D.; Thomas, D. G. T.

doi:10.1097/00002826-198412000-00005

Cited by 15 publications

(7 citation statements)

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“…Whether subclinical involvement really account for our results, magnetic resonance imaging and single-photonemission computed tomography studies could be useful to clarify this point. Second, it is known that corticosteroid therapy affects astrocyte parameters, such as glial fibrillary acidic protein and glutamine synthase expression (22). However, to our knowledge, steroid effects on S100B expression were reported only in vitro (13).…”

Section: Discussionmentioning

confidence: 91%

Serum S100B Levels in Patients with Lupus Erythematosus: Preliminary Observation

Portela

Brenol

Walz

et al. 2002

Clin Vaccine Immunol

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S100B is an astrocytic calcium-binding protein which has been proposed as a biochemical marker of brain damage or dysfunction in acute and chronic diseases. We investigated whether serum S100B levels could be related to systemic lupus erythematosus (SLE) activity. Patients were grouped as having inactive SLE (ISLE), active SLE without central nervous system (CNS) involvement (ASLE), or active SLE with unequivocal neurologic or psychiatric manifestation (NPSLE). The control group consisted of age-and sex-matched healthy blood donors. S100B levels were determined using a luminescence immunoassay. All SLE groups had higher levels of serum S100B than the control group. Among the SLE groups, significantly higher levels of serum S100B protein were found in the NPSLE group than in the ISLE and ASLE groups, and there was no significant difference in S100B levels between the ISLE and ASLE groups. These preliminary results point to a putative relevance of serum S100B protein levels in SLE patients, specifically concerning CNS involvement present in this disease.Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of a variety of autoantibodies, several biochemical abnormalities, and involvement of multiple organ systems (9). The involvement of the central nervous system (CNS) in SLE, causing neuropsychiatric syndromes (NPSLE), is one of the most serious complications of this disease. The NPSLE can vary from mild forms, such as headaches or mild cognitive deficits, to severe states, such as cerebritis, vascular accidents, or psychosis. Recently, a significant positive association of levels of serum antibodies against the specific astrocytic protein glial fibrillary acidic protein with NPSLE was reported (16), suggesting a neural involvement in its pathophysiology. S100B is a calcium-binding protein expressed and released predominantly by astrocytes (5), and its neurotrophic and gliotrophic actions have been implicated in development and maintenance of the nervous system (2, 4). Furthermore, elevated levels of S100B in cerebrospinal fluid (CSF) and serum could indicate astrocyte activation or blood-brain barrier dysfunction, which allows its study as a marker of CNS injury in some acute and chronic diseases, including brain ischemia (8, 23, 24), brain hemorrhage (3), multiple sclerosis (11), Alzheimer's disease (2, 17), and schizophrenia (12). Accordingly, we previously have demonstrated that serum S100B levels are elevated in patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy or tropical spastic paraparesis but not in asymptomatic HTLV-I-positive patients (21). The present work was performed in order to investigate serum S100B levels in SLE patients with and without CNS activity. MATERIALS AND METHODS Subjects.We measured serum S100B levels in 32 SLE patients monitored at the Rheumatology Service of the Hospital de Clínicas de Porto Alegre. All patients fulfilled the American College of Rheumatology (ACR) (1) criteria for SLE. Patients were grouped...

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Section: Discussionmentioning

confidence: 91%

Serum S100B Levels in Patients with Lupus Erythematosus: Preliminary Observation

Portela

Brenol

Walz

et al. 2002

Clin Vaccine Immunol

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“…Although direct effects of DEX on GFAP expression levels were reported in cultured astrocytes [20][21][22], such effects are unlikely in our cell system, because we did not measure the GFAP expression levels but measured amounts of GFAP + cells and it is unlikely that DEX blocks GFAP expression completely in differentiating NPCs. Furthermore, by using potent and specific inhibitors of both the NFkB (SN50) and the PI3 kinase pathway (wortmannin), we were able to completely reproduce this specific effect of DEX.…”

Section: Discussionmentioning

confidence: 94%

Dexamethasone blocks astroglial differentiation from neural precursor cells

Sabolek

Herborg²,

Schwarz³

et al. 2006

NeuroReport

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In previous studies, we demonstrated functional neuronal and dopaminergic differentiation of fetal mesencephalic neural precursor cells. The major factors for orienting their progeny towards a dopaminergic phenotype are forskolin and interleukin-1beta. Here, we investigated the effects of dexamethasone (10 microM) on neuronal and glial differentiation. Exposure of mesencephalic neural precursor cells to dexamethasone significantly reduces the amount of glial fibrillary acidic protein astroglia, but not of galactocerebrosidase C oligodendroglia, MAP2ab neurons and tyrosine hydroxylase dopaminergic cells. Presuming a possible involvement of the nuclear factor-kappaB pathway, we examined the effects of wortmannin (phosphatidylinositol 3'-kinase inhibitor) and SN50 (nuclear factor-kappaB inhibitor) on gliogenesis. Both wortmannin and SN50 mimicked the effects of dexamethasone suggesting that dexamethasone specifically blocks astroglial differentiation from mesencephalic neural precursor cells most likely via inhibition of the nuclear factor-kappaB pathway.

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“…In addition, GLAST expression and its functionality are prerequisites for proper function of glutamine synthetase and of transmitter clearance in M€ uller cells of the retina (Derouiche and Rauen, 1995;Ishikawa et al, 2011). In astrocytes, it has been demonstrated that decreasing GFAP levels are accompanied by a rise in glutamine synthetase activity and vice versa (Weir and Thomas, 1984;Lieth et al, 1998;Pekny et al, 1999). These findings strongly indicate that changes in the expression and structural organization of GFAP during postnatal development will also affect the trafficking of glutamate transporters to the plasma membrane and the functionality of the glutamate-glutamine cycle.…”

Section: Discussionmentioning

confidence: 99%

Laminar and subcellular heterogeneity of GLAST and GLT‐1 immunoreactivity in the developing postnatal mouse hippocampus

Schreiner

Durry

Aida

et al. 2013

J of Comparative Neurology

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Astrocytes express two sodium-coupled transporters, glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1), which are essential for the maintenance of low extracellular glutamate levels. We performed a comparative analysis of the laminar and subcellular expression profile of GLAST and GLT-1 in the developing postnatal mouse hippocampus by using immunohistochemistry and western blotting and employing high-resolution fluorescence microscopy. Astrocytes were identified by costaining with glial fibrillary acidic protein (GFAP) or S100β. In CA1, the density of GFAP-positive cells and GFAP expression rose during the first 2 weeks after birth, paralleled by a steady increase in GLAST immunoreactivity and protein content. Upregulation of GLT-1 was completed only at postnatal days (P) P20-25 and was thus delayed by about 10 days. GLAST staining was highest along the stratum pyramidale and was especially prominent in astrocytes at P3-5. GLAST immunoreactivity indicated no preferential localization to a specific cellular compartment. GLT-1 exhibited a laminar expression pattern from P10-15 on, with the highest immunoreactivity in the stratum lacunosum-moleculare. At the cellular level, GLT-1 immunoreactivity did not entirely cover astrocyte somata and exhibited clusters at processes. In neonatal and juvenile animals, discrete clusters of GLT-1 were also detected at perivascular endfeet. From these results, we conclude there is a remarkable subcellular heterogeneity of GLAST and GLT-1 expression in the developing hippocampus. The clustering of GLT-1 at astrocyte endfeet indicates that it might serve a specialized functional role at the blood-brain barrier during formation of the hippocampal network.

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Effect of Dexamethasone on Glutamine Synthetase and Glial Fibrillary Acidic Protein; in Normal and Transformed Astrocytes

Cited by 15 publications

References 0 publications

Serum S100B Levels in Patients with Lupus Erythematosus: Preliminary Observation

Serum S100B Levels in Patients with Lupus Erythematosus: Preliminary Observation

Dexamethasone blocks astroglial differentiation from neural precursor cells

Laminar and subcellular heterogeneity of GLAST and GLT‐1 immunoreactivity in the developing postnatal mouse hippocampus

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