Neurocentre Magendie

Chantal MEDINA




ITA

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Cursus:
Diplôme d'Ingénieur du CNAM, spécialité Biologie industrielle et agro-alimentaire, Clermont-Ferrand (1991)
Doctorat de l'EPHE, section des sciences de la vie et de la terre, Paris (2008)






12 publication(s) depuis Mai 1995:


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* equal contribution
Les IF indiqués ont été collectés par le Web of Sciences en


23/10/2014 | Cell Rep   IF 7.9
Scribble1/AP2 complex coordinates NMDA receptor endocytic recycling.
Piguel NH, Fievre S, Blanc JM, Carta M, Moreau MM, Moutin E, Pinheiro VL, Medina C, Ezan J, Lasvaux L, Loll F, Durand CM, Chang K, Petralia RS, Wenthold RJ, Stephenson FA, Vuillard L, Darbon H, Perroy J, Mulle C, Montcouquiol M, Racca C, Sans N

Abstract:
The appropriate trafficking of glutamate receptors to synapses is crucial for basic synaptic function and synaptic plasticity. It is now accepted that NMDA receptors (NMDARs) internalize and are recycled at the plasma membrane but also exchange between synaptic and extrasynaptic pools; these NMDAR properties are also key to governing synaptic plasticity. Scribble1 is a large PDZ protein required for synaptogenesis and synaptic plasticity. Herein, we show that the level of Scribble1 is regulated in an activity-dependent manner and that Scribble1 controls the number of NMDARs at the plasma membrane. Notably, Scribble1 prevents GluN2A subunits from undergoing lysosomal trafficking and degradation by increasing their recycling to the plasma membrane following NMDAR activation. Finally, we show that a specific YxxR motif on Scribble1 controls these mechanisms through a direct interaction with AP2. Altogether, our findings define a molecular mechanism to control the levels of synaptic NMDARs via Scribble1 complex signaling.




01/12/2009 | Anal Chem   IF 5.9
Recombinant differential anchorage probes that tower over the spatial dimension of intracellular signals for high content screening and analysis.
Schembri L , Zanese M , Depierre-Plinet G , Petit M , Elkaoukabi-Chaibi A , Tauzin L , Florean C , Lartigue L , Medina C , Rey C , Belloc F , Reiffers J , Ichas F , De Giorgi F

Abstract:
Recombinant fluorescent probes allow the detection of molecular events inside living cells. Many of them exploit the intracellular space to provide positional signals and, thus, require detection by single cell imaging. We describe here a novel strategy based on probes capable of encoding the spatial dimension of intracellular signals into 'all-or-none' fluorescence intensity changes (differential anchorage probes, DAPs). The resulting signals can be acquired in single cells at high throughput by automated flow cytometry, (i) bypassing image acquisition and analysis, (ii) providing a direct quantitative readout, and (iii) allowing the exploration of large experimental series. We illustrate our purpose with DAPs for Bax and the effector caspases 3 and 7, which are keys players in apoptotic cell death, and show applications in basic research, high content multiplexed library screening, compound characterization, and drug profiling.




12/2009 | Cell Res   IF 14.8
Outer membrane VDAC1 controls permeability transition of the inner mitochondrial membrane in cellulo during stress-induced apoptosis.
Tomasello F , Messina A , Lartigue L , Schembri L , Medina C , Reina S , Thoraval D , Crouzet M , Ichas F , De Pinto V , De Giorgi F

Abstract:
Voltage-dependent anion channel (VDAC)1 is the main channel of the mitochondrial outer membrane (MOM) and it has been proposed to be part of the permeability transition pore (PTP), a putative multiprotein complex candidate agent of the mitochondrial permeability transition (MPT). Working at the single live cell level, we found that overexpression of VDAC1 triggers MPT at the mitochondrial inner membrane (MIM). Conversely, silencing VDAC1 expression results in the inhibition of MPT caused by selenite-induced oxidative stress. This MOM-MIM crosstalk was modulated by Cyclosporin A and mitochondrial Cyclophilin D, but not by Bcl-2 and Bcl-X(L), indicative of PTP operation. VDAC1-dependent MPT engages a positive feedback loop involving reactive oxygen species and p38-MAPK, and secondarily triggers a canonical apoptotic response including Bax activation, cytochrome c release and caspase 3 activation. Our data thus support a model of the PTP complex involving VDAC1 at the MOM, and indicate that VDAC1-dependent MPT is an upstream mechanism playing a causal role in oxidative stress-induced apoptosis.




01/11/2008 | J Cell Sci   IF 4.7
An intracellular wave of cytochrome c propagates and precedes Bax redistribution during apoptosis.
Lartigue L , Medina C , Schembri L , Chabert P , Zanese M , Tomasello F , Dalibart R , Thoraval D , Crouzet M , Ichas F , De Giorgi F

Abstract:
Bax is considered to be pivotal in inducing cytochrome c release (CCR) from mitochondria during apoptosis. Indeed, Bax redistributes to the mitochondrial outer membrane (MOM) upon activation and forms homo-multimers that are capable of permeabilizing the MOM. Our attempts to image this sequence of events in single live cells resulted in unexpected observations. Bax redistribution exhibited two distinct components: an early minor redistribution that was silent in terms of homo-multimerization and a major late redistribution that was synchronous with the formation of Bax multimers, but that proceeded belatedly, i.e. only after caspase 3/7 (C3/7) had already been activated. Intriguingly, neither of these two components of redistribution correlated with CCR, which turned out to be spatially organized, propagating as a traveling wave at constant velocity. Strikingly, propagation of the CCR wave (1) preceded signs of in situ Bax conformational activation; (2) appeared to be independent of autocatalytic loops involving a positive feedback of either C3/7, Ca(2+) mobilization or mitochondrial permeability transition; and (3) was triggered by diffuse stimulation with the synthetic Bak activator BH3I-1 but then proceeded independently of Bak activation. Thus, the CCR wave not only questions the exact role of Bax redistribution in cell death, but also indicates the existence of yet unidentified positive-feedback loops that ensure a spatiotemporal control of apoptosis at the subcellular scale.




Abstract:
Schwann cells are best known as myelinating glial cells of the peripheral nervous system, but they also participate actively in the sphere of immunity by producing pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta). In a previous study, we demonstrated that posttranslational processing of IL-1beta by immune-challenged Schwann cells required the P2X7 receptor. Remarkably, the release of IL-1beta was not associated with cell death, indicating the involvement of an active mechanism. ATP binding cassette (ABC) transporters are known to transport leaderless secretory proteins, such as IL-1beta; therefore, we investigated whether such transporters were at work in Schwann cells. Mouse Schwann cells expressed ABC1 transporter mRNA and displayed the functional protein. Glybenclamide and diisothiocyanato-stilbene-disulfonic acid (DIDS), two blockers of chloride fluxes that drive the export activity of ABC1 transporters, inhibited IL-1beta release without altering its intracellular processing. Enhancing chloride efflux potentiated the release of IL-1beta, while decreasing it led to a strong reduction in its release. Because the stimulation of the P2X7 receptor also activates a chloride conductance, we investigated the possibility of a sole anionic pathway mobilized by the P2X7 receptor and ABC1. Glybenclamide and DIDS had no significant effects on the P2X7-activated chloride current suggesting therefore the existence of two different pathways. In summary, ABC1 transporters are required for the release of IL-1beta by mouse Schwann cells. Being associated together with chloride conductance, P2X7 receptors and ABC1 transporters delineate a subtle and complex regulation of IL-1beta production in mammalian Schwann cells. Furthermore, ABC1 transporters could be a target of therapeutic interest for regulating IL-1beta activity in neuroinflammation disorders.




Abstract:
The antidepressant tianeptine has been shown to protect the hippocampus against the deleterious consequences of stress and to attenuate the behavioral and neuroendocrine effects of the cytokine inducer lipopolysaccharide (LPS). Since sickness symptoms are linked to peripheral and brain production of cytokines and pro-inflammatory cytokines can promote neurotoxicity, the present study was undertaken to test the possibility that tianeptine attenuates production of pro-inflammatory cytokines. This hypothesis has been tested by studying the effects of a chronic intraperitoneal (i.p.) administration of tianeptine (10 mg/kg twice a day for 21 days) to rats on the induction by LPS (250 microg/kg, i.p.) of the production of pro- and anti-inflammatory cytokines, at the periphery (spleen, pituitary) and in the brain (hypothalamus, hippocampus). The expression of mRNAs coding for IL-1 beta, TNF-alpha, IL-6 or IL-10 (RT-PCR) and plasma levels of IL-1 beta, TNF-alpha and IL-10 (ELISA) were measured at various time intervals following LPS. Chronic tianeptine treatment attenuated LPS-induced expression of TNF-alpha in the spleen as well as plasma levels of this cytokine and altered the central balance between pro- and anti-inflammatory cytokines (IL-1 beta/IL-10). These results open new vistas in the pharmacological activity of tianeptine and provide further insights on the possible mechanisms of action involved in its neuroprotective properties.




15/08/2003 | J Biol Chem   IF 4.3
Maturation and release of interleukin-1beta by lipopolysaccharide-primed mouse Schwann cells require the stimulation of P2X7 receptors.
Colomar A, Marty V, Medina C, Combe C, Parnet P, Amedee T

Abstract:
The P2X7 receptor, mainly expressed by immune cells, is a ionotropic receptor activated by high concentration of extracellular ATP. It is involved in several processes relevant to immunomodulation and inflammation. Among these processes, the production of extracellular interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, plays a major role in the activation of the cytokine network. We have investigated the role of P2X7 receptor and of an associated calcium-activated potassium conductance (BK channels) in IL-1beta maturation and releasing processes by Schwann cells. Lipopolysaccharide-primed Schwann cells synthesized large amounts of pro-IL-1beta but did not release detectable amounts of pro or mature IL-1beta. ATP on its own had no effect on the synthesis of pro-IL-1beta, but a co-treatment with lipopolysaccharide and ATP led to the maturation and the release of IL-1beta by Schwann cells. Both mechanisms were blocked by oxidized ATP. IL-1beta-converting enzyme (ICE), the caspase responsible for the maturation of pro-IL-1beta in IL-1beta, was activated by P2X7 receptor stimulation. The specific inhibition of ICE by the caspase inhibitor Ac-Tyr-Val-Ala-Asp-aldehyde blocked the maturation of IL-1beta. In searching for a link between the P2X7 receptor and the activation of ICE, we found that enhancing potassium efflux from Schwann cells upregulated the production of IL-1beta, while strongly reducing potassium efflux led to opposite effects. Blocking BK channels actually modulated IL-1beta release. Taken together, these results show that P2X7 receptor stimulation and associated BK channels, through the activation of ICE, leads to the maturation and the release of IL-1beta by immune-challenged Schwann cells.




04/2003 | Brain Behav Immun   IF 5.9
Conditioned place aversion with interleukin-1beta in mice is not associated with activation of the cytokine network.
Mormede C , Castanon N , Medina C , Dantzer R

Abstract:
Several distinct findings argue in favor of conditioning of some components of the acute phase reaction. However, the possibility of a conditioned cytokine response has not been assessed. In the present study, this possibility was tested by submitting mice to place aversion conditioning with interleukin-1beta (2 microgram/mouse, ip) as the unconditioned stimulus and an odorous compartment of a two-compartment cage as the conditioned stimulus. After two pairings, conditioned mice developed place aversion towards the odorous compartment. However, this behavioral conditioning was not accompanied by any alteration in peripheral (spleen) and brain (hypothalamus) cytokine levels (interleukin-1, interleukin-6, and interleukin-10). These data do not support the possibility of conditioned alterations in the cytokine network.




Abstract:
The antidepressant tianeptine has been shown to decrease the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress and to attenuate the behavioral effects of the cytokine inducer, lipopolysaccharide (LPS). Since LPS also activates the HPA axis, the objective of this study was to assess the effects of tianeptine on the HPA axis activation and Fos expression induced by intraperitoneal (i.p.) administration of LPS (30 and 250 microg/kg respectively). Chronic, but not acute, tianeptine treatment (10 mg/kg twice a day for 15 days, i.p.) attenuated LPS-induced increase of plasma ACTH and corticosterone in rats bearing an indwelling catheter in the jugular vein and Fos immunoreactivity in the paraventricular nucleus (PVN). These results open new vistas on the pharmacological activity of tianeptine and provide further insights on the action mechanisms of antidepressants in clinics.




2003 | J Soc Biol
[The immune status of Schwann cells: what is the role of the P2X7 receptor?].
Colomar A, Marty V, Combe C, Medina C, Parnet P, Amedee T

Abstract:
The peripheral nervous system (PNS) displays structural barriers and a lack of lymphatic drainage which strongly limit the access of molecules and cells from the immune system. In addition, the PNS has the ability to set up some specific mechanisms of immune protection to limit the pathogenicity of inflammation processes following insults by pathogens or inflammatory autoimmune diseases like the Guillain-Barre syndrome. Schwann cells are among the most prominent cells which can display immune capabilities in the PNS. Numerous in vitro studies have shown that Schwann cells were indeed able to display a large repertoire of properties, ranging from the participation to antigen presentation, to secretion of pro- and anti-inflammatory cytokines, chemokines and neurotrophic factors. In vivo studies have confirmed the immune capabilities of Schwann cells. The aim of this review is to present how Schwann cells can participate to the initiation, the regulation and the termination of the immune response in the light of the recent discovery of the Schwann cell expression of purinergic P2X7 receptors.