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Reactive glia, including astroglia and oligodendrocyte progenitors (OPCs) are at the core of the reaction to injury in the mammalian brain with initially beneficial and later partially adverse functions such as scar formation. Given the different glial composition in the adult zebrafish brain with radial ependymoglia but no parenchymal astrocytes, we examined the glial response to an invasive stab...
Spinal cord injury (SCI) induces a glial response in which astrocytes become activated and produce inflammatory mediators. The molecular basis for regulation of glial‐innate immune responses remains poorly understood. Here, we examined the activation of retinoic acid‐inducible gene (RIG)‐like receptors (RLRs) and their involvement in regulating inflammation after SCI. We show that astrocytes express...
Myelination is the culmination of a complex process in which oligodendrocyte (OL) progenitors transition through defined stages in a well‐coordinated differentiation program. The signaling mechanisms that regulate this progression are poorly understood. Here we investigate the role of extracellular signal‐regulated‐kinase‐1,‐2 (Erk1/2) and the mammalian target of rapamycin (mTOR), downstream effectors...
Expression of the water channel aquaporin‐4 (AQP4) at the blood–brain interface is dependent upon the dystrophin associated protein complex. Here we investigated whether deletion of the Aqp4 gene affects the molecular composition of this protein scaffold and the integrity of the blood–brain barrier. High‐resolution immunogold cytochemistry revealed that perivascular expression of α‐syntrophin was...
Neuroaxonal degeneration is a pathological hallmark of multiple sclerosis (MS) contributing to irreversible neurological disability. Pathological mechanisms leading to axonal damage include autoimmunity to neuronal antigens. In actively demyelinating lesions, myelin is phagocytosed by microglia and blood‐borne macrophages, whereas the fate of degenerating or damaged axons is unclear. Phagocytosis...
The X‐linked form of Charcot‐Marie‐Tooth disorder (CMTX) is the second most frequent type (15% of CMT forms). It involves the GJB1 gene coding for connexin 32, a protein involved in gap junction formation and function. There is no curative treatment for CMTX. We present data on transgenic lines that was accomplished by inserting a human BAC carrying the GJB1 gene, in which two different mutations...
Cultured astrocytes exhibit a flat/epitelioid phenotype much different from the star‐like phenotype of tissue astrocytes. Upon exposure to treatments that affect the small GTPase Rho and/or its effector ROCK, however, flat astrocytes undergo stellation, with restructuring of cytoskeleton and outgrowth of processes with lamellipodia, assuming a phenotype closer to that exhibited in situ. The mechanisms...
Olfactory ensheathing cells (OECs) play a crucial role during neurogenesis of primary olfactory neurons. Transplantation of OECs is considered as a promising new therapy for central nervous system repair. Nevertheless, OECs are constituted of distinct subpopulations and their role during neurogenesis is not clearly understood. In particular, OECs from the olfactory bulb (OB) constitute a heterogeneous,...
It is currently thought that treatment for spinal cord injury (SCI) will involve a combined pharmacological and biological approach; however, testing their efficacy in animal models of SCI is time‐consuming and requires large animal cohorts. For this reason we have modified our myelinating cultures as an in vitro model of SCI and studied its potential as a prescreen for combined therapeutics. This...
Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide regeneration‐promoting cells recruitable for therapeutic purposes. There is accumulating evidence that aldynoglial cells with Schwann cell‐like growth‐promoting properties emerge in the lesioned CNS. However, the characterization of these cells and the signals triggering their in situ generation...
Fumaric acid esters are used to treat psoriasis, an inflammatory skin disease characterized by keratinocyte proliferation. Inflammation and proliferation are hallmarks of retinal disease; hence, fumaric acid esters may have therapeutic value in retinal pathology. In diseased retinas, Müller glial cells (MCs) undergo reactive gliosis, a hyperproliferative state. MCs take up folate, a vitamin necessary...
High‐grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell‐like capacity. The stem‐like cells may be the cells of origin for tumor relapse. However, the tumor‐associated parenchymal cells such as vascular...
The analysis of the molecular mechanisms involved in the initial interaction between neurons and Schwann cells is a key issue in understanding the myelination process. We recently identified Cthrc1 (Collagen triple helix repeat containing 1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1 encodes a secreted protein previously shown to be involved in migration and proliferation...
SDF‐1/CXCL12 binds to the chemokine receptors, CXCR4 and CXCR7, and controls cell proliferation and migration during development, tumorigenesis, and inflammatory processes. It is currently assumed that CXCR7 would represent an atypical or scavenger chemokine receptor which modulates the function of CXCR4. Contrasting this view, we demonstrated recently that CXCR7 actively mediates SDF‐1 signaling...
The substantial activation of microglia in Japanese encephalitis virus (JEV)‐induced Japanese encephalitis found in numerous studies demonstrates that the disease pathogenesis involves bystander damage caused by microglia‐released mediators. Previously, we reported that microglia synthesized and secreted bioactive mediators with neurotoxic potential into the cultured supernatants in response to JEV...
Sphingosine‐1‐phosphate receptors (S1PRs) are drug targets for the compound FTY720, which is the first oral therapy developed for treatment of relapsing‐remitting multiple sclerosis. S1PRs play a variety of functional roles in the differentiation, proliferation, survival and/or migration of neurons and glia. In this study, rat organotypic cerebellar slice cultures were used to assess whether S1PRs...
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