Astroglial Wiring is Adding Complexity to Neuroglial Networking

Astrocytes are organized as networks of communicating cells due to their high expression level of connexins, the molecular constituents of gap junction channels. Based on their permeability properties for ions and small signaling molecules such astroglial wiring interferes with neuronal activity and survival. In this paper, I identify and discuss which future technical and conceptual progress or advances should be achieved in order to better understand how neuroglial networking contributes to brain functions and dysfunctions

Connexin-dependent neuroglial networking as a new therapeutic target

Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the "tripartite synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength. Connexin-based hemichannels are also involved in those regulations of neuronal activities, however, this feature will not be considered in the present review. Furthermore, neuronal processes, transmitting electrical signals to chemical synapses, stringently control astroglial connexin expression, and channel functions. Long-range energy trafficking toward neurons through connexin-coupled astrocytes and plasticity of those networks are hence largely dependent on neuronal activity. Such reciprocal interactions between neurons and astrocyte networks involve neurotransmitters, cytokines, endogenous lipids, and peptides released by neurons but also other brain cell types, including microglial and endothelial cells. Over the past 10 years, knowledge about neuroglial interactions has widened and now includes effects of CNS-targeting drugs such as antidepressants, antipsychotics, psychostimulants, or sedatives drugs as potential modulators of connexin function and thus astrocyte networking activity. In physiological situations, neuroglial networking is consequently resulting from a two-way interaction between astrocyte gap junction-mediated networks and those made by neurons. As both cell types are modulated by CNS drugs we postulate that neuroglial networking may emerge as new therapeutic targets in neurological and psychiatric disorders

Le chœur dans les luttes d’Aristophane. Rôle et évolution des interventions du chœur dans les scènes d’agôn chez Aristophane

Résumé L’Ancienne Comédie est un genre théâtral très particulier composés d’éléments qui lui sont propres et qui restent singuliers. Le chœur et l’agôn, présents tous les deux dans la genèse du théâtre, font partie des éléments constitutifs de  l’Ancienne Comédie. Au cœur de la tradition grecque depuis la période mythique ils sont des piliers de l’avènement théâtral qui eut pour berceau l’Athènes du V° siècle av. J.-C. Inhérents à l’esprit compétitif grec, ils ont trouvé dans l’Ancienne Coméd..

The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes

In the brain, astrocytes represent the cellular population that expresses the highest amount of connexins (Cxs). This family of membrane proteins is the molecular constituent of gap junction channels and hemichannels that provide pathways for direct cytoplasm-to-cytoplasm and inside-out exchange, respectively. Both types of Cx channels are permeable to ions and small signaling molecules allowing astrocytes to establish dynamic interactions with neurons. So far, most pharmacological approaches currently available do not distinguish between these two channel functions, stressing the need to develop new specific molecular tools. In astrocytes two major Cxs are expressed, Cx43 and Cx30, and there is now evidence indicating that at least Cx43 operates as a gap junction channel as well as a hemichannel in these cells. Based on studies in primary cultures as well as in acute hippocampal slices, we report here that Gap 19, a nonapeptide derived from the cytoplasmic loop of Cx43, inhibits astroglial Cx43 hemichannels in a dose-dependent manner, without affecting gap junction channels. This peptide, which not only selectively inhibits hemichannels but is also specific for Cx43, can be delivered in vivo in mice as TAT-Gap19, and displays penetration into the brain parenchyma. As a result, Gap 19 combined with other tools opens up new avenues to decipher the role of Cx43 hemichannels in interactions between astrocytes and neurons in physiological as well as pathological situations

Communication jonctionnelle et interactions neuro-glio-vasculaires

Responsable : Christian Giaume Dans le système nerveux central, les connexines, protéines constituantes des jonctions communicantes (JCs) ou gap junctions et des hémicannaux, sont exprimées en grande quantité dans les cellules gliales, en particulier dans les astrocytes. Les travaux de notre équipe portent principalement sur différents aspects des propriétés et des rôles de ces protéines dans les interactions que les cellules gliales établissent avec les neurones et le système vasculaire que ..

Optical in situ size determination of single lanthanide-ion doped oxide nanoparticles

International audienceWe show that the size of a lanthanide-ion doped nanoparticle can be accurately determined from its luminosity. The optically determined size distribution is in very good agreement with the distribution obtained from transmission electron microscopy. These data confirm that single nanoparticles are visualized in microscopy experiments. Nanoparticles as small as 13 nm are detectable with integration times of 500 ms. (c) 2006 American Institute of Physics

Glial connexin expression and function in the context of Alzheimer's disease

AbstractA hallmark of neurodegenerative diseases is the reactive gliosis characterized by a phenotypic change in astrocytes and microglia. This glial response is associated with modifications in the expression and function of connexins (Cxs), the proteins forming gap junction channels and hemichannels. Increased Cx expression is detected in most reactive astrocytes located at amyloid plaques, the histopathological lesions typically present in the brain of Alzheimer's patients and animal models of the disease. The activity of Cx channels analyzed in vivo as well as in vitro after treatment with the amyloid β peptide is also modified and, in particular, hemichannel activation may contribute to neuronal damage. In this review, we summarize and discuss recent data that suggest glial Cx channels participate in the neurodegenerative process of Alzheimer's disease. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics

L’impact de la concentration sur la discrimination par les prix dans le transport aérien.

Cet article analyse la relation entre la concentration et la discrimination par les prix sur les routes aériennes en Europe. Nous estimons l'impact des restrictions sur les prix afin d'évaluer la discrimination. Les données de prix ont été collectées de manière séquentielle et portent sur l'ensemble des routes aériennes européennes desservies au départ de l'aéroport Nice Côte d'Azur. Notre analyse empirique montre que la concentration, mesurée par l'inégalité des parts de marchés des compagnies, diminue la sensibilité, en valeur absolue, des prix aux restrictions. Cela implique que la discrimination par les prix est plus faible sur les routes les plus concentrées.concentration;discrimination par les prix;dispersion des prix;marché aérien;Airlines;concentration;Price discrimination;Price dispersion;

Inhibition of astroglial connexin43 hemichannels with TAT-Gap19 exerts anticonvulsant effects in rodents

Accumulating evidence shows a key function for astrocytic connexin43 (Cx43) signaling in epilepsy. However, the lack of experimental distinction between Cx43 gap junction channels (GJCs) and hemichannels (HCs) has impeded the identification of the exact contribution of either channel configurations to epilepsy. We therefore investigated whether TAT-Gap19, a Cx mimetic peptide that inhibits Cx43 HCs but not the corresponding Cx43 GJCs, influences experimentally induced seizures in rodents. Dye uptake experiments in acute hippocampal slices of mice demonstrated that astroglial Cx43 HCs open in response to the chemoconvulsant pilocarpine and this was inhibited by TAT-Gap19. In vivo, pilocarpine-induced seizures as well as the accompanying increase in D-serine microdialysate levels were suppressed by Cx43 HC inhibition. Moreover, the anticonvulsant action of TAT-Gap19 was reversed by exogenous D-serine administration, suggesting that Cx43 HC inhibition protects against seizures by lowering extracellular D-serine levels. The anticonvulsive properties of Cx43 HC inhibition were further confirmed in electrical seizure mouse models, i.e. an acute 6 Hertz (Hz) model of refractory seizures and a chronic 6 Hz corneal kindling model. Collectively, these results indicate that Cx43 HCs play a role in seizures and underscore their potential as a novel and druggable target in epilepsy treatment