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Upregulation of expression of the close homolog of adhesion molecule L1 (CHL1) by reactive astrocytes in the glial scar reduces axonal regeneration and inhibits functional recovery after spinal cord injury (SCI). Here, we investigate the molecular mechanisms underlying upregulation of CHL1 expression by analyzing the signal transduction pathways in vitro. We show that astrogliosis stimulated by bacterial...
Mammalian protoplasmic astrocytes are extensively coupled through gap junction channels but the biophysical properties of these channels under physiological and ischemic conditions in situ are not well defined. Using confocal morphometric analysis of biocytin‐filled astrocytic syncytia in rat hippocampal CA1 stratum radiatum we found that each astrocyte directly couples, on average, to 11 other astrocytes...
With the increasing prevalence of HIV‐associated neurocognititve disorders (HAND), understanding the mechanisms by which HIV‐1 induces neuro‐inflammation and subsequent neuronal damage is important. The hallmark features of HIV‐encephalitis, the pathological correlate of HIV‐associated Dementia (HAD), are gliosis, oxidative stress, chemokine dysregulation, and neuronal damage/death. Since neurons...
Glutamine synthetase (GS) is a key enzyme in the “glutamine‐glutamate cycle” between astrocytes and neurons, but its function in vivo was thus far tested only pharmacologically. Crossing GSfl/lacZ or GSfl/fl mice with hGFAP‐Cre mice resulted in prenatal excision of the GSfl allele in astrocytes. “GS‐KO/A” mice were born without malformations, did not suffer from seizures, had a suckling reflex, and...
It is now widely accepted that resident central nervous system (CNS) cells such as microglia and astrocytes initiate and/or augment inflammation following trauma or infection. However, the mechanisms by which glial cells perceive microbial challenges are only now becoming apparent. We have recently demonstrated that microglia and astrocytes constitutively express nucleotide‐binding oligomerization...
Neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of postnatal mice, and cultured as neurospheres, expressed functional mGlu3 receptors. Following mitogen withdrawal and plating onto poly‐ornitine‐coated dishes, cells dissociated from the neurospheres differentiated into GFAP+ astrocytes (about 85%), and a small percentage of β‐III tubulin+‐neurons and O1+‐oligodendrocytes. Activation...
The lack of markers for astrocytes, particularly gray matter astrocytes, significantly hinders research into their development and physiological properties. We previously reported that fibroblast growth factor receptor 3 (Fgfr3) is expressed by radial precursors in the ventricular zone of the embryonic neural tube and subsequently by differentiated astrocytes in gray and white matter. Here, we describe...
Neuroglobin (Ngb) is proposed to be a neuron‐specific, hypoxia‐responsive, neuroprotective protein. However, results are conflicting concerning both Ngb's physiological and pathological significance. This study was designed to investigate the in vivo localization and regulation of Ngb in different neuropathological models representing traumatic injury, infectious, autoimmune, and excitotoxic pathogeneses...
Vascular/parenchymal crosstalk is increasingly recognized as important in the development and maintenance of healthy vascularized tissues. The retina is an excellent model in which to study the role of cell type‐specific contributions to the process of blood vessel and neuronal growth. During retinal vascular development, glial cells such as astrocytes provide the template over which endothelial cells...
Alexander disease is a rare and usually fatal neurological disorder characterized by the abundant presence of protein aggregates in astrocytes. Most cases result from dominant missense de novo mutations in the gene encoding glial fibrillary acidic protein (GFAP), but how these mutations lead to aggregate formation and compromise function is not known. A transgenic mouse line (Tg73.7) over‐expressing...
In utero alcohol exposure can lead to fetal alcohol spectrum disorders, characterized by cognitive and behavioral deficits. In vivo and in vitro studies have shown that ethanol alters neuronal development. We have recently shown that stimulation of M3 muscarinic receptors in astrocytes increases the synthesis and release of fibronectin, laminin, and plasminogen activator inhibitor‐1, causing neurite...
Manganese in excess is neurotoxic and causes CNS injury resembling that of Parkinson's disease. In brain, astrocytes predominantly take up and accumulate manganese and are thus vulnerable to its toxicity. Manganese was shown to induce cell swelling in cultured astrocytes, and oxidative/nitrosative stress (ONS) mediates such swelling. As aquaporin‐4 (AQP4) is important in the mechanism of astrocyte...
HIV‐1 Tat protein is an important pathogenic factor in HIV‐1‐associated neurological diseases. One hallmark of HIV‐1 infection of the central nervous system (CNS) is astrocytosis, which is characterized by elevated glial fibrillary acidic protein (GFAP) expression in astrocytes. We have shown that Tat activates GFAP expression in astrocytes [Zhou et al., (2004) Mol Cell Neurosci 27:296–305] and that...
While astrocytes produce key inflammatory mediators following exposure to neurotropic nonsegmented negative‐sense RNA viruses such as rabies virus and measles virus, the mechanisms by which resident central nervous system (CNS) cells perceive such viral challenges have not been defined. Recently, several cytosolic DExD/H box RNA helicases including retinoic acid‐inducible gene I (RIG‐I) have been...
Accumulating evidence suggests that spinal astrocytes play an important role in the genesis of persistent pain, by increasing the activity of spinal cord nociceptive neurons, i.e., central sensitization. However, direct evidence of whether activation of astrocytes is sufficient to induce chronic pain symptoms is lacking. We investigated whether and how spinal injection of activated astrocytes could...
Actin‐depolymerizing factor (ADF)/cofilin is a small cytoskeletal protein that is a stimulus‐responsive mediator of actin dynamics. ADF/cofilin also translocates into mitochondria and nuclei in response to apoptotic stimuli for cytochrome c release. These ADF/cofilin translocations are negatively regulated by phosphorylation. Recently, it has been reported that pyridoxal‐5′‐phosphate (PLP) phosphatase/chronophin...
Jaundice and sepsis are common neonatal conditions that can lead to neurodevelopment sequelae, namely if present at the same time. We have reported that tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β are produced by cultured neurons and mainly by glial cells exposed to unconjugated bilirubin (UCB). The effects of these cytokines are mediated by cell surface receptors through a nuclear factor...
Reactive astrocytosis, involving activation, hypertrophy, and proliferation of astrocytes, is a characteristic response to inflammation or injury of the central nervous system. We have investigated whether inhibition of reactive astrocytosis influences established experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We made use of transgenic mice, which express herpes...
It has been hypothesized that neuroinflammation triggered during brain development can alter brain functions later in life. We investigated the contribution of inflammation to the alteration of normal brain circuitries in the context of neuroexcitotoxicity following neonatal ventral hippocampal lesions in rats with ibotenic acid, an NMDA glutamate receptor agonist. Excitotoxic ibotenic acid lesions...
The impact of connexin30 (Cx30) on interastrocytic gap junction coupling in the normal hippocampus is matter of debate; reporter gene analyses indicated a weak expression of Cx30 in the mouse hippocampus. In contrast, mice lacking connexin43 (Cx43) in astrocytes exhibited only 50% reduction in coupling. Complete uncoupling of hippocampal astrocytes in mice lacking both Cx30 and Cx43 suggested that...
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