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Search Results: 1 - 10 of 403241 matches for " Isabelle M. Mansuy "
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Distinct molecular components for thalamic- and cortical-dependent plasticity in the lateral amygdala
Osvaldo Mirante,Johannes Bohacek,Isabelle M. Mansuy
Frontiers in Molecular Neuroscience , 2014, DOI: 10.3389/fnmol.2014.00062
Abstract: N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala (LA) is a form of synaptic plasticity thought to be a cellular substrate for the extinction of fear memory. The LA receives converging inputs from the sensory thalamus and neocortex that are weakened following fear extinction. Combining field and patch-clamp electrophysiological recordings in mice, we show that a paired-pulse low-frequency stimulation can induce a robust LTD at thalamic and cortical inputs to LA, and we identify different underlying molecular components at these pathways. We show that while LTD depends on NMDARs and activation of the protein phosphatases PP2B and PP1 at both pathways, it requires NR2B-containing NMDARs at the thalamic pathway, but NR2C/D-containing NMDARs at the cortical pathway. LTD appears to be induced postsynaptically at the thalamic input but presynaptically at the cortical input, since postsynaptic calcium chelation and NMDAR blockade prevent thalamic but not cortical LTD. These results highlight distinct molecular features of LTD in LA that may be relevant for traumatic memory and its erasure, and for pathologies such as post-traumatic stress disorder (PTSD).
Inheritable Effect of Unpredictable Maternal Separation on Behavioral Responses in Mice
Isabelle C. Weiss,Tamara B. Franklin,Isabelle M. Mansuy
Frontiers in Behavioral Neuroscience , 2011, DOI: 10.3389/fnbeh.2011.00003
Abstract: The long-term impact of early stress on behavior and emotions is well documented in humans, and can be modeled in experimental animals. In mice, maternal separation during early postnatal development induces poor and disorganized maternal care, and results in behavioral deficits that persist through adulthood. Here, we examined the long-term effect of unpredictable maternal separation combined with maternal stress on behavior and its transmissibility. We report that unpredictable maternal separation from birth to postnatal day 14 in C57Bl/6J mice has mild behavioral effects in the animals when adult, but that its combination with maternal stress exacerbates this effect. Further, the behavioral deficits are transmitted to the following generation through females, an effect that is independent of maternal care and is not affected by cross-fostering. The combined manipulation does not alter basic components of the hypothalamic–pituitary–adrenal axis but decreases the expression of the corticotropin releasing factor receptor 2 (CRFR2) in several nuclei of the amygdala and the hypothalamus in the brain of maternal-separated females. These results suggest a non-genomic mode of transmission of the impact of early stress in mice.
The Principle of Legality and the Execution of Sentences in France and Germany: Law= Rights?
Isabelle Mansuy
Champ Pénal , 2008, DOI: 10.4000/champpenal.3263
Abstract: In the German legal system, prison law is part of a larger system of laws designed for the protection of fundamental rights; in France, prison law seems to be paralyzed by its lack of a legislative foundation. However, in both countries, the everyday world of incarceration remains one that is governed by the need to maintain order and security, to the detriment of the avowed purposes of imprisonment. The question then becomes: is the law effective in allowing the exercise of rights in prison?
Principe de légalité et d'exécution des peines en France et Allemagne, Droit = droits ? The Principle of Legality and the Execution of Sentences in France and Germany: Law= Rights?
Isabelle Mansuy
Champ Pénal , 2009, DOI: 10.4000/champpenal.397
Abstract: Dans l’ordre juridique allemand, le droit pénitentiaire est une matière construite et structurée autour d’une loi, qui s’intègre dans un mode de protection des droits fondamentaux élaboré ; en France, le droit pénitentiaire semble embourbé dans son défaut de fondement législatif. Pourtant, ici et là, le quotidien carcéral reste un monde régi par les priorités du maintien de l’ordre et de la sécurité, au détriment des missions attribuées à la peine privative de liberté. D’où la question de l’efficacité du droit à rendre possible l’exercice de droits derrière les barreaux. In Germany the detention legal framework is structured around a law which is integrated in a developed system of protection of human rights; in France, the penitentiary legal system seems to be jammed by the lack of a legislative foundation. However, the daily life in prison remains governed by the maintenance of order and security, to the detriment of the missions assigned to the imprisonment. Hence, the question whether the law can effectively make possible the exercise of rights behind bars. Full Text
Protein Phosphatase 1 (PP1) Is a Post-Translational Regulator of the Mammalian Circadian Clock
Isabelle Schmutz, Sabrina Wendt, Anna Schnell, Achim Kramer, Isabelle M. Mansuy, Urs Albrecht
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021325
Abstract: Circadian clocks coordinate the timing of important biological processes. Interconnected transcriptional and post-translational feedback loops based on a set of clock genes generate and maintain these rhythms with a period of about 24 hours. Many clock proteins undergo circadian cycles of post-translational modifications. Among these modifications, protein phosphorylation plays an important role in regulating activity, stability and intracellular localization of clock components. Several protein kinases were characterized as regulators of the circadian clock. However, the function of protein phosphatases, which balance phosphorylation events, in the mammalian clock mechanism is less well understood. Here, we identify protein phosphatase 1 (PP1) as regulator of period and light-induced resetting of the mammalian circadian clock. Down-regulation of PP1 activity in cells by RNA interference and in vivo by expression of a specific inhibitor in the brain of mice tended to lengthen circadian period. Moreover, reduction of PP1 activity in the brain altered light-mediated clock resetting behavior in mice, enhancing the phase shifts in either direction. At the molecular level, diminished PP1 activity increased nuclear accumulation of the clock component PER2 in neurons. Hence, PP1, may reduce PER2 phosphorylation thereby influencing nuclear localization of this protein. This may at least partially influence period and phase shifting properties of the mammalian circadian clock.
Influence of Early Stress on Social Abilities and Serotonergic Functions across Generations in Mice
Tamara B. Franklin,Natacha Linder,Holger Russig,Beat Th?ny,Isabelle M. Mansuy
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0021842
Abstract: Exposure to adverse environments during early development is a known risk factor for several psychiatric conditions including antisocial behavior and personality disorders. Here, we induced social anxiety and altered social recognition memory in adult mice using unpredictable maternal separation and maternal stress during early postnatal life. We show that these social defects are not only pronounced in the animals directly subjected to stress, but are also transmitted to their offspring across two generations. The defects are associated with impaired serotonergic signaling, in particular, reduced 5HT1A receptor expression in the dorsal raphe nucleus, and increased serotonin level in a dorsal raphe projection area. These findings underscore the susceptibility of social behaviors and serotonergic pathways to early stress, and the persistence of their perturbation across generations.
Selective Regulation of NR2B by Protein Phosphatase-1 for the Control of the NMDA Receptor in Neuroprotection
Mélissa Farinelli, Fabrice D. Heitz, Benjamin F. Grewe, Shiva K. Tyagarajan, Fritjof Helmchen, Isabelle M. Mansuy
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034047
Abstract: An imbalance between pro-survival and pro-death pathways in brain cells can lead to neuronal cell death and neurodegeneration. While such imbalance is known to be associated with alterations in glutamatergic and Ca2+ signaling, the underlying mechanisms remain undefined. We identified the protein Ser/Thr phosphatase protein phosphatase-1 (PP1), an enzyme associated with glutamate receptors, as a key trigger of survival pathways that can prevent neuronal death and neurodegeneration in the adult hippocampus. We show that PP1α overexpression in hippocampal neurons limits NMDA receptor overactivation and Ca2+ overload during an excitotoxic event, while PP1 inhibition favors Ca2+ overload and cell death. The protective effect of PP1 is associated with a selective dephosphorylation on a residue phosphorylated by CaMKIIα on the NMDA receptor subunit NR2B, which promotes pro-survival pathways and associated transcriptional programs. These results reveal a novel contributor to the mechanisms of neuroprotection and underscore the importance of PP1-dependent dephosphorylation in these mechanisms. They provide a new target for the development of potential therapeutic treatment of neurodegeneration.
Identification of Combinatorial Patterns of Post-Translational Modifications on Individual Histones in the Mouse Brain
Ry Y. Tweedie-Cullen, Andrea M. Brunner, Jonas Grossmann, Safa Mohanna, David Sichau, Paolo Nanni, Christian Panse, Isabelle M. Mansuy
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036980
Abstract: Post-translational modifications (PTMs) of proteins are biochemical processes required for cellular functions and signalling that occur in every sub-cellular compartment. Multiple protein PTMs exist, and are established by specific enzymes that can act in basal conditions and upon cellular activity. In the nucleus, histone proteins are subjected to numerous PTMs that together form a histone code that contributes to regulate transcriptional activity and gene expression. Despite their importance however, histone PTMs have remained poorly characterised in most tissues, in particular the brain where they are thought to be required for complex functions such as learning and memory formation. Here, we report the comprehensive identification of histone PTMs, of their combinatorial patterns, and of the rules that govern these patterns in the adult mouse brain. Based on liquid chromatography, electron transfer, and collision-induced dissociation mass spectrometry, we generated a dataset containing a total of 10,646 peptides from H1, H2A, H2B, H3, H4, and variants in the adult brain. 1475 of these peptides carried one or more PTMs, including 141 unique sites and a total of 58 novel sites not described before. We observed that these PTMs are not only classical modifications such as serine/threonine (Ser/Thr) phosphorylation, lysine (Lys) acetylation, and Lys/arginine (Arg) methylation, but also include several atypical modifications such as Ser/Thr acetylation, and Lys butyrylation, crotonylation, and propionylation. Using synthetic peptides, we validated the presence of these atypical novel PTMs in the mouse brain. The application of data-mining algorithms further revealed that histone PTMs occur in specific combinations with different ratios. Overall, the present data newly identify a specific histone code in the mouse brain and reveal its level of complexity, suggesting its potential relevance for higher-order brain functions.
Antidepressant therapy with milnacipran and venlafaxine
Lucilla Mansuy
Neuropsychiatric Disease and Treatment , 2010,
Abstract: Lucilla MansuyPierre Fabre Médicament, Toulouse, FranceAbstract: Specific serotonin norepinephrine reuptake inhibitors (SNRIs) have been described as “better tolerated tricyclic antidepressants” or as “boosted” selective serotonin reuptake inhibitors (SSRIs). Venlafaxine has become a therapeutic reference treatment for major depression. Although less widely studied, indirect comparisons with another SNRI, milnacipran, suggest an equivalent efficacy. This paper discusses these indirect comparisons and the recently published first double-blind, head-to-head comparison. Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses. To overcome the problem of the differing profile of venlafaxine at increasing doses, the first head-to-head study compared the therapeutic effects and tolerability of the two antidepressants when flexibly titrated to the high dose of 200 mg/day. The study showed that the two SNRIs have similar efficacy and safety profiles. Both drugs produced about 42% remissions at the end of the 20-week study. The most frequent adverse events in both groups were nausea, dizziness, headache, and sweating. Certain specific differences in tolerability are discussed.Keywords: milnacipran, venlafaxine, antidepressant efficacy, tolerability, dose-titration
Algèbres de greffes
Anthony Mansuy
Mathematics , 2011,
Abstract: In order to study some sets of probabilities, called induced averages by J. Ecalle, F. Menous introduces two grafting operators $ B^{+} $ and $ B^{-} $. With these two operators, we construct Hopf algebras of rooted and ordered trees $ \mathcal{B}^{i} $, $ i \in \mathbb{N}^{\ast} $, $ \mathcal{B}^{\infty} $ and $ \mathcal{B} $ satisfying the inclusion relations $ \mathcal{B}^{1} \subseteq \hdots \mathcal{B}^{i} \subseteq \mathcal{B}^{i+1} \subseteq \hdots \subseteq \mathcal{B}^{\infty} \subseteq \mathcal{B} $. We endow $ \mathcal{B} $ with a structure of duplicial dendriform bialgebra and we deduce that $ \mathcal{B} $ is cofree and self-dual. Finally, we introduce the notion of bigraft algebra and we prove that $ \mathcal{B} $ is generated as bigraft algebra by the element $ \tdun{1} $.
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