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Murviel-lès-Montpellier, France

Marchi N.,Cleveland Clinic | Lerner-Natoli M.,French National Center for Scientific Research | Lerner-Natoli M.,French Institute of Health and Medical Research | Lerner-Natoli M.,Universites Of Montpellier 1 And 2
Neuroscientist | Year: 2013

The role of the blood-brain barrier (BBB) in epilepsy has evolved from an obstacle for drug brain delivery to an etiological factor contributing to seizures. Recent evidence has shown cerebrovascular angiogenesis and increased BBB permeability in the epileptic foci of patients and in experimental models of seizure. The molecular players involved in cerebrovascular remodeling in the epileptic brain are similar to those reported for other brain disorders. The question arises whether pharmacological solutions restoring a proper BBB permeability and preventing dysregulated angiogenesis could be also beneficial in mitigating seizures. We now summarize the available data supporting the role of vascular remodeling and angiogenesis in the epileptic brain, taking into account that the BBB is a multi-cellular structure, reacting to physiological and pathological stimuli. Drugs targeting aberrant angiogenesis could be beneficial in reducing seizure burden when used in combination with available anti-epileptic drugs. We also offer an overview of novel cellular players, such as pericytes, which may participate in cerebrovascular remodeling in the epileptic brain. The possible role of angiogenesis in drug-resistant forms of epilepsy associated with neurovascular dysplasia is discussed. Finally, we speculate on whether the formation of leaky BBB vessels could have an impact on the cerebrovascular rheology and on the physiological mechanisms regulating brain homeostasis. © The Author(s) 2012. Source

Dalle S.,French National Center for Scientific Research | Dalle S.,French Institute of Health and Medical Research | Dalle S.,Universites Of Montpellier 1 And 2 | Burcelin R.,French Institute of Health and Medical Research | And 2 more authors.
Cellular Signalling | Year: 2013

Type 2 diabetes occurs when the β-cells do not secrete enough insulin to counter balance insulin resistance. GLP-1 and GIP are insulinotropic peptides which are thought to benefit to β-cell physiology. On one hand sustained pharmacological levels of GLP-1 are achieved by subcutaneous administration of GLP-1 analogs while transient and lower physiological levels of GLP-1 are attained following DPP4 inhibitor (DPP4i) treatment. On the other hand, DPP4i increase GLP-1 concentration into the portal vein to recruit the gut-to brain-to pancreas axis which is not the case with injected analogs. Hence, these differences between GLP-1 analogs and DPP4i indicate that both strategies could differentially impact β-cell behavior. Here, we summarize the effects of GLP-1 analogs and DPP4i on β-cell physiology. We discuss the possibility that production of signaling molecules, such as cAMP, generated into the β-cells by native GLP-1 or pharmacological GLP-1 analogs may vary and engage different downstream signaling networks. Hence, deciphering which signaling networks are engaged following GLP-1 analogs or DPP4i administration appears to be critical to unveil the contribution of each treatment/strategy to engage β-cell cellular processes. © 2012 Elsevier Inc. Source

Baneres J.-L.,Max Mousseron Institute of Biomolecules | Baneres J.-L.,Universites Of Montpellier 1 And 2 | Popot J.-L.,CNRS Molecular Chemistry Laboratory | Popot J.-L.,University Paris Diderot | And 3 more authors.
Trends in Biotechnology | Year: 2011

G-protein-coupled receptors (GPCRs), the largest family of integral membrane proteins, participate in the regulation of many physiological functions and are the targets of approximately 30% of currently marketed drugs. However, knowledge of the structural and molecular bases of GPCR functions remains limited owing to difficulties related to their overexpression, purification and stabilization. The development of new strategies aimed at obtaining large amounts of functional GPCRs is therefore crucial. Here, we review the most recent advances in the production and functional folding of GPCRs from Escherichia coli inclusion bodies. Major breakthroughs open exciting perspectives for structural and dynamic investigations of GPCRs. In particular, combining targeting to bacterial inclusion bodies with amphipol-assisted folding is emerging as a highly powerful strategy. © 2011 Elsevier Ltd. Source

Meziane H.,Institute Of La Clinique Of La Souris | Schaller F.,French Institute of Health and Medical Research | Bauer S.,French Institute of Health and Medical Research | Villard C.,Plateforme Proteomique et Innovation Technologique Timone | And 6 more authors.
Biological Psychiatry | Year: 2015

Background Mutations of MAGEL2 have been reported in patients presenting with autism, and loss of MAGEL2 is also associated with Prader-Willi syndrome, a neurodevelopmental genetic disorder. This study aimed to determine the behavioral phenotype of Magel2-deficient adult mice, to characterize the central oxytocin (OT) system of these mutant mice, and to test the curative effect of a peripheral OT treatment just after birth. Methods We assessed the social and cognitive behavior of Magel2-deficient mice, analyzed the OT system of mutant mice treated or not by a postnatal administration of OT, and determined the effect of this treatment on the brain. Results Magel2 inactivation induces a deficit in social recognition and social interaction and a reduced learning ability in adult male mice. In these mice, we reveal anatomical and functional modifications of the OT system and show that these defects change from birth to adulthood. Daily administration of OT in the first postnatal week was sufficient to prevent deficits in social behavior and learning abilities in adult mutant male mice. We show that this OT treatment partly restores a normal OT system. Thus, we report that an alteration of the OT system around birth has long-term consequences on behavior and on cognition. Importantly, an acute OT treatment of Magel2-deficient pups has a curative effect. Conclusions Our study reveals that OT plays a crucial role in setting social behaviors during a period just after birth. An early OT treatment in this critical period could be a novel therapeutic approach for the treatment of neurodevelopmental disorders such as Prader-Willi syndrome and autism. © 2015 Society of Biological Psychiatry. Source

Jopling C.,Universites Of Montpellier 1 And 2 | Belmonte J.C.I.,Salk Institute for Biological Studies
Cell Cycle | Year: 2012

Although adult mammals are unable to significantly regenerate their heart, this is not the case for a number of other vertebrate species. In particular, zebrafish are able to fully regenerate their heart following amputation of up to 20% of the ventricle. Soon after amputation, cardiomyocytes dedifferentiate and proliferate to regenerate the missing tissue. More recently, identical results have also been obtained in neonatal mice. Ventricular amputation of neonates leads to a robust regenerative response driven by the proliferation of existing cardiomyocytes in a similar manner to zebrafish. However, this ability is progressively lost during the first week of birth. The fact that adult zebrafish retain the capacity to regenerate their heart suggests that they either possess a unique regenerative mechanism, or that adult mammals lose/ inhibit this process. p38α MAPK has previously been shown to negatively regulate the proliferation of adult mammalian cardiomyocytes. We sought to determine whether a similar mechanism exists in adult zebrafish, and whether this needs to be overcome to allow regeneration to proceed. To determine whether p38α MAPK also regulates zebrafish cardiomyocytes in a similar manner, we generated conditional transgenic zebrafish in which either dominant-negative or active p38α MAPK are specifically expressed in cardiomyocytes. We found that active p38α MAPK but not dominant-negative p38α MAPK blocks proliferation of adult zebrafish cardiomyocytes and, consequently, heart regeneration as well. It appears that adult zebrafish cardiomyocytes share many characteristics with adult mammalian cardiomyocytes, including p38α MAPK-mediated cell cycle inhibition. These findings raise the possibility that zebrafish-like heart regeneration could be achieved in adult mammals. © 2012 Landes Bioscience. Source

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