Search results for "Astrocyte"
showing 10 items of 209 documents
Caveolin and GLT-1 gene expression is reciprocally regulated in primary astrocytes: Association of GLT-1 with non-caveolar lipid rafts
2004
Caveolae represent membrane microdomains acting as integrators of cellular signaling and functional processes. Caveolins are involved in the biogenesis of caveolae and regulate the activity of caveolae-associated proteins. Although caveolin proteins are found in the CNS, the regulation of caveolins in neural cells is poorly described. In the present study, we investigated different modes and mechanisms of caveolin gene regulation in primary rat astrocytes. We demonstrated that activation of cAMP-dependent signaling pathways led to a marked reduction in protein levels of caveolin-1/-2 in cortical astrocytes. Application of transforming growth factor-alpha (TGF-alpha) also resulted in a decre…
Pharmacological Suppression of CNS Scarring by Deferoxamine Reduces Lesion Volume and Increases Regeneration in an In Vitro Model for Astroglial-Fibr…
2015
Lesion-induced scarring is a major impediment for regeneration of injured axons in the central nervous system (CNS). The collagen-rich glial-fibrous scar contains numerous axon growth inhibitory factors forming a regeneration-barrier for axons. We demonstrated previously that the combination of the iron chelator 2,2'-bipyridine-5,5'-decarboxylic acid (BPY-DCA) and 8-Br-cyclic AMP (cAMP) inhibits scar formation and collagen deposition, leading to enhanced axon regeneration and partial functional recovery after spinal cord injury. While BPY-DCA is not a clinical drug, the clinically approved iron chelator deferoxamine mesylate (DFO) may be a suitable alternative for anti-scarring treatment (A…
OTUB1 inhibits CNS autoimmunity by preventing IFN-γ-induced hyperactivation of astrocytes.
2019
Astrocytes are critical regulators of neuroinflammation in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Growing evidence indicates that ubiquitination of signaling molecules is an important cell‐intrinsic mechanism governing astrocyte function during MS and EAE. Here, we identified an upregulation of the deubiquitinase OTU domain, ubiquitin aldehyde binding 1 (OTUB1) in astrocytes during MS and EAE. Mice with astrocyte‐specific OTUB1 ablation developed more severe EAE due to increased leukocyte accumulation, proinflammatory gene transcription, and demyelination in the spinal cord as compared to control mice. OTUB1‐deficient astrocytes were hy…
Differential Promotion of Glutamate Transporter Expression and Function by Glucocorticoids in Astrocytes from Various Brain Regions
2005
Steroids that activate glucocorticoid receptors (GRs) and mineralocorticoid receptors have important regulatory effects on neural development, plasticity, and the body's stress response. Here, we investigated the role of corticosteroids in regulating the expression of the glial glutamate transporters glial glutamate transporter-1 (GLT-1) and glutamate-aspartate transporter (GLAST) in rat primary astrocytes. The synthetic glucocorticoid dexamethasone provoked a marked increase of GLT-1 transcription and protein levels in cortical astrocytes, whereas GLAST expression remained unaffected. Up-regulation of GLT-1 expression was accompanied by an enhanced glutamate uptake, which could be blocked …
Production of ceramides causes apoptosis during early neural differentiation in vitro.
2000
To investigate signal transduction pathways leading to apoptosis during the early phase of neurogenesis, we employed PCC7-Mz1 cells, which cease to proliferate and begin to differentiate into a stable pattern of neurons, astroglial cells, and fibroblasts upon incubation with retinoic acid (RA). As part of lineage determination, a sizable fraction of RA-treated cultures die by apoptosis. Applying natural long-chain C(16)-ceramides as well as membrane-permeable C(2)/C(6)-ceramide analogs caused apoptosis, whereas the biologically nonactive C(2)-dihydroceramide did not. Treating PCC7-Mz1 stem cells with a neutral sphingomyelinase or with the ceramidase inhibitor N-oleoylethanolamine elevated t…
Cortical astrocytosis in juvenile rhesus monkeys infected with simian immunodeficiency virus
1993
The pattern of expression of GFAP immunoreactivity in astrocytes of the juvenile rhesus monkey cortex was examined following infection with simian immunodeficiency virus (SIV). Blocks of cerebral cortex plus subjacent white matter from saline- and formalin-perfused brain were examined by peroxidase-linked immunochemical and immunofluorescence staining of deparaffinized sections. Strong GFAP immunoreactivity was found in astrocytic cells in both uninfected and SIV-infected juvenile macaque in the subpial cerebral cortex and in subcortical white matter, where GFAP-positive cells were abundant. GFAP staining of cortical layers 2-6 on the other hand was weak or absent in three uninfected contro…
Mammalian glial cells in culture synthesize acetylcholine.
1997
In the present study we demonstrate that acetylcholine is synthesized by cultured mammalian glial cells identified by cell-type specific markers. Primary cultures of rat brain astrocytes or microglia contained 2.0 and 1.6 pmol acetylcholine/10(6) cells on average respectively. Astrocyte cultures established from neonatal mouse brain contained even more acetylcholine (about 80 pmol acetylcholine/10(6) cells). Primary cultures of rat brain astrocytes showed choline acetyltransferase (ChAT) enzyme activity of 3 nmol/mg protein/h; ChAT activity was blocked by 10 microM bromoacetylcholine. In conclusion, these data demonstrate the synthesis of the "neurotransmitter" acetylcholine in cultured gli…
Neuronal Bioenergetics and Acute Mitochondrial Dysfunction: A Clue to Understanding the Central Nervous System Side Effects of Efavirenz
2014
Background. Neurological pathogenesis is associated with mitochondrial dysfunction and differences in neuronal/glial handling of oxygen and glucose. The main side effects attributed to efavirenz involve the CNS, but the underlying mechanisms are unclear. Methods. Human cell lines and rat primary cultures of neurons and astrocytes were treated with clinically relevant efavirenz concentration. Results. Efavirenz alters mitochondrial respiration, enhances reactive oxygen species generation, undermines mitochondrial membrane potential, and reduces adenosine triphosphate (ATP) levels in a concentration-dependent fashion in both neurons and glial cells. However, it activates adenosine monophospha…
Biosynthesis and maintenance of GSH in primary astrocyte cultures: role of L-cystine and ascorbate.
1995
Abstract We have studied the optimal conditions to maintain the astrocyte GSH levels under normal and oxidative stress conditions. The rate of GSH synthesis from l -methionine was statistically lower than from l -cystine or N -acetyl-cysteine in astrocytes treated with diethyl-maleate, which is substrate of GSH S-transferases. This is in accordance with the fact that cystathionase activity was not detectable. The transport of l -cystine mediated by the Na + -independent system Xc − is the limiting step in GSH synthesis in astrocytes. Incubation with tert-butyl hydroperoxide (t-booH) reduced GSH concentration in astrocytes. This reduction was ameliorated in part by the addition of ascorbate …
Editorial: Hypoxia and Cardiorespiratory Control
2021
To maintain adequate oxygen levels in the body, which is essential for a healthy life, the respiratory and cardiovascular systems play vitally important roles. When the oxygen content is insufficient, i.e., when hypoxia is loaded, respiratory and cardiovascular systems respond to restore, compensate, or adapt to hypoxia, e.g., by increasing ventilation and blood flow to maintain oxygen transport to vital organs. Traditionally, it has been thought that hypoxia is detected solely by carotid and aortic bodies, i.e., by peripheral chemoreceptors, and information from the peripheral chemoreceptors is transmitted to respiratory and cardiovascular centers in the brainstem whose respiratory and car…