Institute Of Recherche Biomedicale Des Armees Irba

Brétigny-sur-Orge, France

Institute Of Recherche Biomedicale Des Armees Irba

Brétigny-sur-Orge, France
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Tronche C.,Institute Of Recherche Biomedicale Des Armees Irba | Lestage P.,Institute Of Recherches Servier | Louis C.,Institute Of Recherches Servier | Carrie I.,Toulouse University Hospital Center | Beracochea D.,French National Center for Scientific Research
Behavioural Brain Research | Year: 2010

Episodic memory deficits in elderly are due to the progressive weaknesses to use the contextual and temporal cues of the to be remembered information. Since the inability to remember the specific context of events is an important feature of episodic memory deficits in the elderly, we first focused on describing two mice models of contextual " episodic-like" memory. In a second part, we described the effects of aging on memory in the contextual and serial discrimination (CSD) task. We showed more specifically that the CSD task allowed detection of early memory impairments in middle-aged (14-15 months) animals as compared to young (4-5 months) or aged (18-19 months) ones. Interestingly, the very same memory impairments were observed following dorsal hippocampal lesions in young adult mice, which suggest that the CSD task allowed detection of early signs of age-related hippocampal dysfunction. In a third part, we showed that pharmacological reference compounds such as donepezil and memantine (mainly used in the treatment of mild to severe forms of Alzheimer's diseases) reversed the age-induced memory impairments as well as emerging pharmacological compounds acting on different neurotransmitter targets (nicotinic and AMPA receptors).Thus, the CSD task appears to be a reliable behavioural tool for detecting the early emergence of age-related memory dysfunction and for identifying new pharmacological targets and therapeutic strategies in the treatment of age-related amnesia. © 2010 Elsevier B.V.

Berthet M.,University of Lyon | Gauthier Y.,Institute Of Recherche Biomedicale Des Armees Irba | Lacroix C.,University of Lyon | Verrier B.,University of Lyon | Monge C.,University of Lyon
Trends in Biotechnology | Year: 2017

Reconstructing functional skin after a wound remains a challenge due to the complexity of healing. In this regard, biocompatible nanoparticles (NPs) carrying and releasing bioactive drugs in a controlled and sustained manner may significantly improve the efficacy of wound therapies compared with current treatments. Topical administration of drug-loaded NPs allows optimal delivery to the dermis and improves product efficacy. Furthermore, associating NPs with scaffolds represents a new concept of 'dressing'. Experimental in vivo, ex vivo, and in vitro models have been developed in preclinical assays to evaluate the beneficial effects of nanoparticulate dressings. Drug-loaded NPs are promising tools for innovative wound healing treatment, especially with regard to their multifunctional properties. Nanoparticles (NPs) loaded with drugs such as growth factors or nucleic acids are promising tools for skin regeneration and represent a strategy for wound repair.Their incorporation into an 'intelligent' matrix to design a nanocomposite (NCP) gives rise to innovative dressings.Significant efforts are made to develop 'green processes' aimed at producing biocompatible composites. A successful outcome of these NCPs would result in a sequential release of loaded drugs following the healing process stages.Recent advances in alternative models to animal experimentation focus on in vitro human reconstructed skin cultured in static conditions. In vitro organ-on-a-chip techniques will allow the integration of microfluidic networks with 3D tissue-engineered models. This research field opens new windows for preclinical NP screening. © 2017 Elsevier Ltd.

Cian C.,Institute Of Recherche Biomedicale Des Armees Irba
Experimental brain research | Year: 2014

The aim of the present study was to investigate (1) the relative contribution of the egocentric reference as well as body orientation perception to visual horizon percept during tilt or during increased gravito-inertial acceleration (GiA, hypergravity environment) conditions and (2) the role of vestibular signals in the inter-individual differences observed in these perceptual modalities. Perceptual estimates analysis showed that backward tilt induced (1) an elevation of the visual horizon, (2) an elevation of the egocentric estimation (visual straight ahead) and (3) an overestimation of body tilt. The increase in the magnitude of GiA induced (1) a lowering of the apparent horizon, (2) a lowering of the straight ahead and (3) a perception of backward tilt. Overall, visual horizon percept can be expressed as the combination of body orientation perception and egocentric estimation. When assessing otolith reactivity using off-vertical axis rotation (OVAR), only visual egocentric estimation was significantly correlated with horizontal OVAR performance. On the one hand, we found a correlation between a low modulation amplitude of the otolith responses and straight ahead accuracy when the head axis was tilted relative to gravity. On the other hand, the bias of otolith responses was significantly correlated with straight ahead accuracy when subjects were submitted to an increase in the GiA. Thus, straight ahead sense would be dependent to some extent to otolith function. These results are discussed in terms of the contribution of otolith inputs in the overall multimodal integration subtending spatial constancy.

Gaveau V.,French Institute of Health and Medical Research | Gaveau V.,University Claude Bernard Lyon 1 | Pisella L.,French Institute of Health and Medical Research | Pisella L.,University Claude Bernard Lyon 1 | And 9 more authors.
Neuropsychologia | Year: 2014

Following the princeps investigations of Marc Jeannerod on action-perception, specifically, goal-directed movement, this review article addresses visual and non-visual processes involved in guiding the hand in reaching or grasping tasks. The contributions of different sources of correction of ongoing movements are considered; these include visual feedback of the hand, as well as the often-neglected but important spatial updating and sharpening of goal localization following gaze-saccade orientation. The existence of an automatic online process guiding limb trajectory toward its goal is highlighted by a series of princeps experiments of goal-directed pointing movements. We then review psychophysical, electrophysiological, neuroimaging and clinical studies that have explored the properties of these automatic corrective mechanisms and their neural bases, and established their generality. Finally, the functional significance of automatic corrective mechanisms-referred to as motor flexibility-and their potential use in rehabilitation are discussed. © 2013 Elsevier Ltd.

Tronche C.,Institute Of Recherche Biomedicale Des Armees Irba | Tronche C.,French National Center for Scientific Research | Pierard C.,Institute Of Recherche Biomedicale Des Armees Irba | Coutan M.,Institute Of Recherche Biomedicale Des Armees Irba | And 3 more authors.
Neurobiology of Learning and Memory | Year: 2010

The present study investigates the relationships between hippocampal corticosterone concentrations and memory retrieval performance in stress and non-stress conditions, in both young (6. month-old) and middle-aged (16. month-old) mice. For this purpose, the time-course evolution of stress-induced corticosterone rise in the dorsal hippocampus (dHPC) was investigated in both young and middle-aged mice. In parallel, the evolution of memory retrieval patterns was assessed using a contextual serial discrimination task (CSD). Finally, metyrapone (corticosterone synthesis inhibitor) was administered in order to evaluate the stress-induced impact of corticosterone rise on contextual memory retrieval in middle-aged animals.Results showed that: (i) non-stressed middle-aged mice exhibited a memory retrieval pattern opposite to that of non-stressed young animals, but similar to that of stressed young mice; (ii) the impact of stress on memory performance was transient (90. min) in young, as compared to middle-aged mice (120. min); (iii) dHPC basal (non-stress) corticosterone level was significantly increased by ageing; (iv) acute stress induced a rapid (15. min) and transient (90. min) dHPC corticosterone rise in young mice, while exhibiting greater magnitude and duration (120. min) in middle-aged animals; and (v) both the stress-induced endocrinal and memory effects were blocked by metyrapone in young and middle-aged mice.Finally, to our knowledge, the present work is the first study to directly measure the corticosterone rise in the hippocampus following exposure to stress and to directly correlate the corticosterone changes in the hippocampus with memory performance in both young and middle-aged mice. © 2009 Elsevier Inc.

Chennaoui M.,Institute Of Recherche Biomedicale Des Armees Irba | Chennaoui M.,University of Paris Descartes | Arnal P.J.,Institute Of Recherche Biomedicale Des Armees Irba | Arnal P.J.,University of Paris Descartes | And 4 more authors.
Sleep Medicine Reviews | Year: 2015

Sleep and exercise influence each other through complex, bilateral interactions that involve multiple physiological and psychological pathways. Physical activity is usually considered as beneficial in aiding sleep although this link may be subject to multiple moderating factors such as sex, age, fitness level, sleep quality and the characteristics of the exercise (intensity, duration, time of day, environment). It is therefore vital to improve knowledge in fundamental physiology in order to understand the benefits of exercise on the quantity and quality of sleep in healthy subjects and patients. Conversely, sleep disturbances could also impair a person's cognitive performance or their capacity for exercise and increase the risk of exercise-induced injuries either during extreme and/or prolonged exercise or during team sports. This review aims to describe the reciprocal fundamental physiological effects linking sleep and exercise in order to improve the pertinent use of exercise in sleep medicine and prevent sleep disorders in sportsmen. © 2014 Elsevier Ltd.

Dorey R.,French National Center for Scientific Research | Dorey R.,Institute Of Recherche Biomedicale Des Armees Irba | Pierard C.,Institute Of Recherche Biomedicale Des Armees Irba | Chauveau F.,Institute Of Recherche Biomedicale Des Armees Irba | And 2 more authors.
Neuropsychopharmacology | Year: 2012

The present study was aimed at determining the relative contribution of the dorsal (DH) and ventral (VH) hippocampus in stress-induced memory retrieval impairments. Thus, we studied the temporal involvement of corticosterone and its receptors, i.e. mineralocorticoid (MR) and glucocorticoid (GR) in the DH and VH, in relation with the time-course evolution of stress-induced memory retrieval impairments. In a first experiment, double microdialysis allowed showing on the same animal that an acute stress (electric footshocks) induced an earlier corticosterone rise in the DH (1560 min post-stress) and then in the VH (90105 min post-stress). The return to baseline was faster in the DH (105 min) than in the VH (120 min). Memory deficits assessed by delayed alternation occurred at 15-, 60-, and 105-min delays after stress and were closely related to the kinetic of corticosterone rises within the DH and VH. In a second experiment, the GR antagonist RU-38486 and the MR antagonist RU-28318 were administered in the DH or VH 15 min before stress. RU-38486 restored memory at 60 but not at 105 min post-stress delays in the DH, whereas the opposite pattern was observed in the VH. By contrast, RU-28318 had no effect on memory impairments at both the 60- and 105-min post-stress delays, showing that MR receptors are not involved at these delays. However, RU-28318 administered in the DH restored memory when administered at a shorter post-stress delay (15 min). Overall, our data are first to evidence that stress induces a functional switch from the DH to VH via different corticosterone time-course evolutions in these areas and the sequential GR receptors involvement in the DH and then in the VH, as regards the persistence of stress-induced memory retrieval deficits over time. © 2012 American College of Neuropsychopharmacology. All rights reserved.

Dorey R.,French National Center for Scientific Research | Dorey R.,Institute Of Recherche Biomedicale Des Armees Irba | Pierard C.,Institute Of Recherche Biomedicale Des Armees Irba | Shinkaruk S.,French Institute of Health and Medical Research | And 5 more authors.
Neuropsychopharmacology | Year: 2011

This study was aimed at determining the type of the glucocorticoid membrane receptors (mineralocorticoid receptors (MRs) or glucocorticoid receptors (GRs)) in the dorsal hippocampus (dHPC) involved in the rapid effects of corticosterone or stress on memory retrieval. For that purpose, we synthesized corticosterone-3-O-carboxymethyloxime-bovine serum albumin conjugate (Cort-3CMO-BSA) conjugate (a high MW complex that cannot cross the cell membrane) totally devoid of free corticosterone, stable in physiological conditions. In a first experiment, we evidenced that an acute stress (electric footshocks) induced both a dHPC corticosterone rise measured by microdialysis and memory retrieval impairment on delayed alternation task. Both the endocrinal and cognitive effects of stress were blocked by metyrapone (a corticosterone synthesis inhibitor). In a second experiment, we showed that bilateral injections of either corticosterone or Cort-3CMO-BSA in dHPC 15 min before memory testing produced impairments similar to those resulting from acute stress. Furthermore, we showed that anisomycin (a protein synthesis inhibitor) failed to block the deleterious effect of Cort-3CMO-BSA on memory. In a third experiment, we evidenced that intra-hippocampal injection of RU-28318 (MR antagonist) but not of RU-38486 (GR antagonist) totally blocked the Cort-3CMO-BSA-induced memory retrieval deficit. In a fourth experiment, we demonstrated that RU-28318 administered 15 min before stress blocked the stress-induced memory impairments when behavioral testing occurred 15 min but not 60 min after stress. Overall, this study provides strong in vivo evidence that the dHPC membrane GRs, mediating the rapid and non-genomic effects of acute stress on memory retrieval, are of MR but not GR type. © 2011 American College of Neuropsychopharmacology. All rights reserved.

Mathieu J.,Institute Of Recherche Biomedicale Des Armees Irba | Mathieu J.,Institute Pasteur Paris
Toxins | Year: 2015

Autophagy is a physiological process involved in defense mechanisms for clearing intracellular bacteria. The autophagic pathway is finely regulated and bacterial toxins interact with this process in a complex manner. Bacterial toxins also interact significantly with many biochemical processes. Evaluations of the effects of bacterial toxins, such as endotoxins, pore-forming toxins and adenylate cyclases, on autophagy could support the development of new strategies for counteracting bacterial pathogenicity. Treatment strategies could focus on drugs that enhance autophagic processes to improve the clearance of intracellular bacteria. However, further in vivo studies are required to decipher the upregulation of autophagy and potential side effects limiting such approaches. The capacity of autophagy activation strategies to improve the outcome of antibiotic treatment should be investigated in the future. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

Holy X.,Institute Of Recherche Biomedicale Des Armees Irba | Collombet J.-M.,Institute Of Recherche Biomedicale Des Armees Irba | Labarthe F.,Center Medical Of Lescadrille Des Sous Marins Nucleaires Lanceurs Dengins | Granger-Veyron N.,Center Medical Of Lescadrille Des Sous Marins Nucleaires Lanceurs Dengins | Begot L.,Institute Of Recherche Biomedicale Des Armees Irba
Journal of Applied Physiology | Year: 2012

The aim of the study was to determine the seasonal influence of vitamin D status on bone metabolism in French submariners over a 2-mo patrol. Blood samples were collected as follows: prepatrol and patrol days 20, 41, and 58 on crewmembers from both a winter (WP; n = 20) and a summer patrol (SP; n = 20), respectively. Vitamin D status was evaluated for WP and SP. Moreover, extended parameters for acidbase balance (PCO 2, pH, and bicarbonate), bone metabolism (bone alkaline phosphatase and COOH-terminal telopeptide of type I collagen), and mineral homeostasis (parathyroid hormone, ionized calcium and phosphorus) were scrutinized. As expected, SP vitamin D status was higher than WP vitamin D status, regardless of the considered experimental time. A mild chronic respiratory acidosis (CRA) was identified in both SP and WP submariners, up to patrol day 41. Such an occurrence paired up with an altered bone remodeling coupling (decreased bone alkaline phosphatase-to-COOH-terminal telopeptide of type I collagen ratio). At the end of the patrol (day 58), a partial compensation of CRA episode, combined with a recovered normal bone remodeling coupling, was observed in SP, not, however, in WP submariners. The mild CRA episode displayed over the initial 41-day submersion period was mainly induced by a hypercapnia resulting from the submarine-enriched CO 2 level. The correlated impaired bone remodeling may imply a physiological attempt to compensate this acidosis via bone buffering. On patrol day 58, the discrepancy observed in terms of CRA compensation between SP and WP may result from the seasonal influence on vitamin D status. Copyright © 2012 the American Physiological Society.

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