Emerging neurotrophic role of GABAB receptors in neuronal circuit development

The proper development of highly organized structures in the central nervous system is a complex process during which key events – neurogenesis, migration, growth, differentiation, and synaptogenesis – have to take place in an appropriate manner to create functional neuronal networks. It is now well established that GABA, the main inhibitory neurotransmitter in the adult mammalian brain, plays more than a classical inhibitory role and can function as an important developmental signal early in life. GABA binds to chloride-permeable ionotropic GABA(A) receptors and to G-protein-coupled GABA(B) receptors (GABA(B)-Rs). Although most of the trophic actions of GABA have been attributed to the activation of GABA(A) receptors, recent advances show that GABA(B)-Rs also regulate fundamental steps of network development. This review summarizes some of the recent progress about the neurotrophic role of GABA(B)-Rs to neuronal development

Relationship between Fungal Colonisation of the Respiratory Tract in Lung Transplant Recipients and Fungal Contamination of the Hospital Environment

International audienceBackgroundAspergillus colonisation is frequently reported after lung transplantation. The question of whether aspergillus colonisation is related to the hospital environment is crucial to prevention.MethodTo elucidate this question, a prospective study of aspergillus colonisation after lung transplantation, along with a mycological survey of the patient environment, was performed.ResultsForty-four consecutive patients were included from the day of lung transplantation and then examined weekly for aspergillus colonisation until hospital discharge. Environmental fungal contamination of each patient was followed weekly via air and surface sampling. Twelve patients (27%) had transient aspergillus colonisation, occurring 1–13 weeks after lung transplantation, without associated manifestation of aspergillosis. Responsible Aspergillus species were A. fumigatus (6), A. niger (3), A. sydowii (1), A. calidoustus (1) and Aspergillus sp. (1). In the environment, contamination by Penicillium and Aspergillus was predominant. Multivariate analysis showed a significant association between occurrence of aspergillus colonisation and fungal contamination of the patient’s room, either by Aspergillus spp. in the air or by A.fumigatus on the floor. Related clinical and environmental isolates were genotyped in 9 cases of aspergillus colonisation. For A. fumigatus (4 cases), two identical microsatellite profiles were found between clinical and environmental isolates collected on distant dates or locations. For other Aspergillus species, isolates were different in 2 cases; in 3 cases of aspergillus colonisation by A. sydowii, A. niger and A. calidoustus, similarity between clinical and environmental internal transcribed spacer and tubulin sequences was >99%.ConclusionTaken together, these results support the hypothesis of environmental risk of hospital acquisition of aspergillus colonisation in lung transplant recipients

Management of Kaposi sarcoma after solid organ transplantation:A European retrospective study

Background: Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes: reduction of immunosuppression, conversion to mammalian target of rapamycin (mTOR) inhibitors, chemotherapy, or a combination of these.Objective: To obtain an overview of clinical strategies about the current treatment of KS.Methods: We conducted a multicenter retrospective cohort study including 145 solid organ transplant recipients diagnosed with KS between 1985 and 2011 to collect data regarding first-line treatment and response at 6 months.Results: Overall, 95%, 28%, and 16% of patients had reduction of immunosuppression, conversion to mTOR inhibitor, and chemotherapy, respectively. Patients treated with chemotherapy or mTOR inhibitor conversion were more likely to have visceral KS. At 6 months, 83% of patients had response, including 40% complete responses.Limitations: The retrospective design of the study.Conclusion: Currently available therapeutic options seem to be effective to control KS in most patients. Tapering down the immunosuppressive regimen remains the cornerstone of KS management.Dermatology-oncolog

Innovation et développement dans les systèmes agricoles et alimentaires

L’innovation est souvent présentée comme l’un des principaux leviers pour promouvoir un développement plus durable et plus inclusif. Dans les domaines de l’agriculture et de l’alimentation, l’innovation est marquée par des spécificités liées à sa relation à la nature, mais aussi à la grande diversité d’acteurs concernés, depuis les agriculteurs jusqu’aux consommateurs, en passant par les services de recherche et de développement. L’innovation émerge des interactions entre ces acteurs, qui mobilisent des ressources et produisent des connaissances dans des dispositifs collaboratifs, afin de générer des changements. Elle recouvre des domaines aussi variés que les pratiques de production, l’organisation des marchés, ou les pratiques alimentaires. L’innovation est reliée aux grands enjeux de développement : innovation agro-écologique, innovation sociale, innovation territoriale, etc. Cet ouvrage porte un regard sur l’innovation dans les systèmes agricoles et alimentaires. Il met un accent particulier sur l’accompagnement de l’innovation, en interrogeant les méthodes et les organisations, et sur l’évaluation de l’innovation au regard de différents critères. Il s’appuie sur des réflexions portées par différentes disciplines scientifiques, sur des travaux de terrain conduits tant en France que dans de nombreux pays du Sud, et enfin sur les expériences acquises en accompagnant des acteurs qui innovent. Il combine des synthèses sur l’innovation et des études de cas emblématiques pour illustrer les propos. L’ouvrage est destiné aux enseignants, professionnels, étudiants et chercheurs

Mechanism of BDNF Modulation in GABAergic Synaptic Transmission in Healthy and Disease Brains

In the mature healthy mammalian neuronal networks, γ-aminobutyric acid (GABA) mediates synaptic inhibition by acting on GABAA and GABAB receptors (GABAAR, GABABR). In immature networks and during numerous pathological conditions the strength of GABAergic synaptic inhibition is much less pronounced. In these neurons the activation of GABAAR produces paradoxical depolarizing action that favors neuronal network excitation. The depolarizing action of GABAAR is a consequence of deregulated chloride ion homeostasis. In addition to depolarizing action of GABAAR, the GABABR mediated inhibition is also less efficient. One of the key molecules regulating the GABAergic synaptic transmission is the brain derived neurotrophic factor (BDNF). BDNF and its precursor proBDNF, can be released in an activity-dependent manner. Mature BDNF operates via its cognate receptors tropomyosin related kinase B (TrkB) whereas proBDNF binds the p75 neurotrophin receptor (p75NTR). In this review article, we discuss recent finding illuminating how mBDNF-TrkB and proBDNF-p75NTR signaling pathways regulate GABA related neurotransmission under physiological conditions and during epilepsy

Rôle des cellules interstitielles de Cajal dans l'activité autorythmique du tractus gastro-intestinal

Les cellules interstitielles de Cajal (CIC) sont des cellules impliquées principalement dans l'activité autorythmique du tractus digestif. Notre étude concerne les mécanismes à l'origine des ondes lentes (DL) générées par les CIC. Nous avons montré, au niveau de l'estomac de souris, que la fréquence des DL antrales est la même que celle du corps lorsque les CIC de ces deux régions sont interconnectées. Chez les témoins, le pacemaker dominant est situé au niveau de la région proximale du corps et impose sa fréquence à tout l'organe. Chez les souris WN-Jv, le réseau de CIC est altéré au niveau du corps. La fréquence imposée à l'organe provient alors de propriétés intrinsèques acquises par les CIC antrales qui déchargent à une fréquence plus élevée que chez les témoins. Comme la fréquence de l'organe est similaire à celle des témoins, l'apparition de pacemakers dominants antraux pourrait traduire qu'un mécanisme de compensation visant à pallier à la défaillance des CIC du corps s'est mis en place. L'altération des réseaux de CIC s'accompagne presque invariablement de profondes perturbations de la motricité digestive. Nous avons montré qu'à l'inverse, les dysfonctionnements observés chez les patients atteints de la maladie de Crohn s'accompagnent de la disparition des CIC situées dans les couches musculaires. Par contre, nous n'avons pas observé de modification des CIC localisées au niveau des plexus myentériques, du plexus musculaire profond et des septa. Nos travaux contribuent à montrer l'importance des CIC dans la genèse de l'activité pacemaker et ouvrent des perspectives nouvelles de recherche se rapportant aux altérations de la motricité digestive.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Activity-dependent dendritic secretion of brain-derived neurotrophic factor modulates synaptic plasticity

International audienc

Mechanism of BDNF Modulation in GABAergic Synaptic Transmission in Healthy and Disease Brains

International audienceIn the mature healthy mammalian neuronal networks, γ-aminobutyric acid (GABA) mediates synaptic inhibition by acting on GABA A and GABA B receptors (GABA A R, GABA B R). In immature networks and during numerous pathological conditions the strength of GABAergic synaptic inhibition is much less pronounced. In these neurons the activation of GABA A R produces paradoxical depolarizing action that favors neuronal network excitation. The depolarizing action of GABA A R is a consequence of deregulated chloride ion homeostasis. In addition to depolarizing action of GABA A R, the GABA B R mediated inhibition is also less efficient. One of the key molecules regulating the GABAergic synaptic transmission is the brain derived neurotrophic factor (BDNF). BDNF and its precursor proBDNF, can be released in an activity-dependent manner. Mature BDNF operates via its cognate receptors tropomyosin related kinase B (TrkB) whereas proBDNF binds the p75 neurotrophin receptor (p75 NTR). In this review article, we discuss recent finding illuminating how mBDNF-TrkB and proBDNF-p75 NTR signaling pathways regulate GABA related neurotransmission under physiological conditions and during epilepsy