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Aquaporin‐4 (AQP4) is the principle water channel and the primary route for water transport across astrocytic membranes. AQP4 co‐localizes with Kir4.1 channels at astrocytic endfeet, and it has been suggested that these channels cooperate in K+ and water homeostasis. In response to injury, two additional aquaporins, AQP1 and AQP9, can be detected in astrocytes, yet neither is found in cultured astrocytes,...
Neuron–glia communication is essential for regulating the properties of synaptic connections in the brain. Astrocytes, in particular, play a critical and complex role in synapse development, maintenance, and plasticity. Likewise, neurons reciprocally influence astrocyte physiology. However, the molecular signaling events that enable astrocytes and neurons to effectively communicate with each other...
Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll‐like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond as strongly as microglia to TLR agonists remains contentious. In this study, we have rigorously purified astrocytes...
Müller glia, the major type of glia in the retina, are mitotically quiescent under normal conditions, though they can be stimulated to proliferate in some pathological states. Among these stimuli, EGF is known to be a potent mitogen for Müller glia. However, the signaling pathways required for EGF‐mediated proliferation of Müller glia are not clearly understood. In this study, postnatal day 12 (P12)...
Satellite glial cells (SGCs) surrounding primary sensory neurons are similar to astrocytes of the central nervous system in that they buffer the extracellular environment via potassium and calcium channels and express the intermediate filament glial fibrillary acidic protein (GFAP). Peripheral nerve injury induces a reactive state in SGCs that includes SGC proliferation, increased SGC/SGC coupling...
Accumulative evidence indicates that microglial cells influence the normal development of central nervous system (CNS) synapses. Yet, the functional properties of microglia in relation with synapse development remain unclear. We recently showed that in layer 4 of the whisker‐related barrel field of the mouse somatosensory cortex, microglial cells are recruited only after postnatal day (P)5 in the...
The G protein‐coupled receptor EBI2 (Epstein–Barr virus‐induced gene 2) is activated by 7α, 25‐dihydroxycholesterol (7α25HC) and plays a role in T cell‐dependant antibody response and B cell migration. Aberrant EBI2 signaling is implicated in a range of autoimmune disorders however its role in the CNS remains unknown. Here we characterize the functional role of EBI2 in GLIA cells using primary human...
The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes...
The straightforward concept that accentuated Wnt signaling via the Wnt‐receptor‐β‐catenin‐TCF/LEF cascade (also termed canonical Wnt signaling or Wnt/β‐catenin signaling) delays or blocks oligodendrocyte differentiation is very appealing. According to this concept, canonical Wnt signaling is responsible for remyelination failure in multiple sclerosis and for persistent hypomyelination in periventricular...
We used proximity‐dependent biotin identification (BioID) to find proteins that potentially interact with the major glial glutamate transporter, GLT‐1, and we studied how these interactions might affect its activity. GTPase Rac1 was one protein identified, and interfering with its GTP/GDP cycle in mixed primary rat brain cultures affected both the clustering of GLT‐1 at the astrocytic processes and...
This review discusses aspects of known and putative compartmentalized 3′,5′‐cyclic adenosine monophosphate (cAMP) signaling in astrocytes, a cell type that has turned out to be a key player in brain physiology and pathology. cAMP has attracted less attention than Ca2+ in recent years, but could turn out to rival Ca2+ in its potential to drive cellular functions and responses to intra— and extracellular...
The electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), is the major bicarbonate transporter expressed in astrocytes. It is highly sensitive for bicarbonate and the main regulator of intracellular, extracellular, and synaptic pH, thereby modulating neuronal excitability. However, despite these essential functions, the molecular mechanisms underlying NBCe1‐mediated astrocytic response...
The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor expressed on myeloid‐derived cell types. The extracellular immunoglobulin‐like domain of TREM2 binds anionic ligands including Apolipoprotein E and Amyloid‐β. The transmembrane domain interacts with its adaptor protein DAP12/TYROBP that is responsible for propagation of downstream signaling upon ligand interaction...
In the central nervous system, oligodendrocytes synthesize the myelin, a specialized membrane to wrap axons in a discontinuous way allowing a rapid saltatory nerve impulse conduction. Oligodendrocytes express a number of growth factors and neurotransmitters receptors that allow them to sense the environment and interact with neurons and other glial cells. Depending on the cell cycle stage, oligodendrocytes...
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