Search results for "Transduction"
showing 10 items of 2149 documents
IkappaB kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-kappaB in the central nervous system
2011
The IκB kinase complex induces nuclear factor kappa B activation and has recently been recognized as a key player of autoimmunity in the central nervous system. Notably, IκB kinase/nuclear factor kappa B signalling regulates peripheral myelin formation by Schwann cells, however, its role in myelin formation in the central nervous system during health and disease is largely unknown. Surprisingly, we found that brain-specific IκB kinase 2 expression is dispensable for proper myelin assembly and repair in the central nervous system, but instead plays a fundamental role for the loss of myelin in the cuprizone model. During toxic demyelination, inhibition of nuclear factor kappa B activation by …
Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.
2014
There is epidemiological evidence that patients with certain Central Nervous System (CNS) disorders have a lower than expected probability of developing some types of Cancer. We tested here the hypothesis that this inverse comorbidity is driven by molecular processes common to CNS disorders and Cancers, and that are deregulated in opposite directions. We conducted transcriptomic meta-analyses of three CNS disorders (Alzheimer's disease, Parkinson's disease and Schizophrenia) and three Cancer types (Lung, Prostate, Colorectal) previously described with inverse comorbidities. A significant overlap was observed between the genes upregulated in CNS disorders and downregulated in Cancers, as wel…
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…
Role of Sortilin in Models of Autoimmune Neuroinflammation
2015
Abstract The proneurotrophin receptor sortilin is a protein with dual functions, being involved in intracellular protein transport, as well as cellular signal transduction. The relevance of the receptor for various neuronal disorders, such as dementia, seizures, and brain injury, is well established. In contrast, little is known about the role of sortilin in immune cells and inflammatory diseases. The aim of our study was to elucidate the distribution of sortilin in different immune cell types in mice and humans and to analyze its function in autoimmune CNS inflammation. Sortilin was expressed most profoundly in murine and human macrophages and dendritic cells and to a much lesser extent in…
Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System
2015
SummaryDuring early embryogenesis, microglia arise from yolk sac progenitors that populate the developing central nervous system (CNS), but how the tissue-resident macrophages are maintained throughout the organism’s lifespan still remains unclear. Here, we describe a system that allows specific, conditional ablation of microglia in adult mice. We found that the microglial compartment was reconstituted within 1 week of depletion. Microglia repopulation relied on CNS-resident cells, independent from bone-marrow-derived precursors. During repopulation, microglia formed clusters of highly proliferative cells that migrated apart once steady state was achieved. Proliferating microglia expressed …
The evolutionary history and tissue mapping of GPR123: specific CNS expression pattern predominantly in thalamic nuclei and regions containing large …
2007
The Adhesion family of G protein-coupled receptors (GPCRs) includes 33 receptors and is the second largest GPCR family. Most of these proteins are still orphans and fairly little is known of their tissue distribution and evolutionary context. We report the evolutionary history of the Adhesion family protein GPR123 as well as mapping of GPR123 mRNA expression in mouse and rat using in situ hybridization and real-time PCR, respectively. GPR123 was found to be well conserved within the vertebrate lineage, especially within the transmembrane regions and in the distal part of the cytoplasmic tail, containing a potential PDZ binding domain. The real-time PCR data indicates that GPR123 is predomin…
Central Modulatory Neurons Control Fuel Selection in Flight Muscle of Migratory Locust
2003
Insect flight is one of the most intense and energy-demanding physiological activities. High carbohydrate oxidation rates are necessary for take-off, but, to spare the limited carbohydrate reserves, long-distance flyers, such as locusts, soon switch to lipid as the main fuel. We demonstrate that before a flight, locust muscles are metabolically poised for take-off by the release of octopamine from central modulatory dorsal unpaired median (DUM) neurons, which increases the levels of the potent glycolytic activator fructose 2,6-bisphosphate in flight muscle. Because DUM neurons innervating the flight muscles are active during rest but selectively inhibited during flight, they stimulate carbo…
Induction of identified mesodermal cells by CNS midline progenitors in Drosophila.
1997
ABSTRACT The Drosophila ventral midline cells generate a discrete set of CNS lineages, required for proper patterning of the ventral ectoderm. Here we provide the first evidence that the CNS midline cells also exert inductive effects on the mesoderm. Mesodermal progenitors adjacent to the midline progenitor cells give rise to ventral somatic mucles and a pair of unique cells that come to lie dorsomedially on top of the ventral nerve cord, the so-called DM cells. Cell ablation as well as cell transplantation experiments indicate that formation of the DM cells is induced by midline progenitors in the early embryo. These results are corroborated by genetic analyses. Mutant single minded embryo…
Noncompetitive agonism at nicotinic acetylcholine receptors; functional significance for CNS signal transduction.
1995
The alkaloids (-)physostigmine (Phy), galanthamine (Gal) and codeine (Cod), and several derivatives and homologous compounds, can act as noncompetitive agonists (NCA) of nicotinic acetylcholine receptors (nAChR) from Torpedo electrocytes, frog and mammalian muscle cells, clonal rat pheochromocytoma cells, cultured hippocampal neurons and several ectopic expression systems, by interacting with a binding site on the alpha-subunits of these nAChRs that is insensitive to the natural transmitter, acetylcholine (ACh), and ACh-competitive agonists and antagonists. Several endogenous ligands, including opioid-type compounds, can also act via this site, albeit at higher concentrations than is typica…
Differential effects of EGF receptor signalling on neuroblast lineages along the dorsoventral axis of the Drosophila CNS
1998
ABSTRACT The Drosophila ventral nerve cord derives from a stereotype population of about 30 neural stem cells, the neuroblasts, per hemineuromere. Previous experiments provided indications for inductive signals at ventral sites of the neuroectoderm that confer neuroblast identities. Using cell lineage analysis, molecular markers and cell transplantation, we show here that EGF receptor signalling plays an instructive role in CNS patterning and exerts differential effects on dorsoventral subpopulations of neuroblasts. The Drosophila EGF receptor (DER) is capable of cell autonomously specifiying medial and intermediate neuroblast cell fates. DER signalling appears to be most critical for prope…