38 research outputs found

    Melatonin Promotes Oligodendroglial Maturation of Injured White Matter in Neonatal Rats

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    OBJECTIVE:To investigate the effects of melatonin treatment in a rat model of white matter damage (WMD) in the developing brain. Additionally, we aim to delineate the cellular mechanisms of melatonin effect on the oligodendroglial cell lineage. METHODS:A unilateral ligation of the uterine artery in pregnant rat at the embryonic day 17 induces fetal hypoxia and subsequent growth restriction (GR) in neonatal pups. GR and control pups received a daily intra-peritoneal injection of melatonin from birth to post-natal day (P) 3. RESULTS:Melatonin administration was associated with a dramatic decrease in microglial activation and astroglial reaction compared to untreated GR pups. At P14, melatonin prevented white matter myelination defects with an increased number of mature oligodendrocytes (APC-immunoreactive) in treated GR pups. Conversely, melatonin was not found to be associated with an increased density of total oligodendrocytes (Olig2-immunoreactive), suggesting that melatonin is able to promote oligodendrocyte maturation but not proliferation. These effects appear to be melatonin-receptor dependent and were reproduced in vitro. INTERPRETATION:These data suggest that melatonin has a strong protective effect on developing damaged white matter through decreased microglial activation and oligodendroglial maturation leading to a normalization of the myelination process. Consequently, melatonin should be a considered as an effective neuroprotective candidate not only in perinatal brain damage but also in inflammatory and demyelinating diseases observed in adults

    Neurotensin Receptor 1 Gene (NTSR1) Polymorphism Is Associated with Working Memory

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    BACKGROUND: Recent molecular genetics studies showed significant associations between dopamine-related genes (including genes for dopamine receptors, transporters, and degradation) and working memory, but little is known about the role of genes for dopamine modulation, such as those related to neurotensin (NT), in working memory. A recent animal study has suggested that NT antagonist administration impaired working memory in a learning task. The current study examined associations between NT genes and working memory among humans. METHODS: Four hundred and sixty healthy undergraduate students were assessed with a 2-back working memory paradigm. 5 SNPs in the NTSR1 gene were genotyped. 5 ANOVA tests were conducted to examine whether and how working memory differed by NTSR1 genotype, with each SNP variant as the independent variable and the average accuracy on the working memory task as the dependent variable. RESULTS: ANOVA results suggested that two SNPs in the NTSR1 gene (rs4334545 and rs6090453) were significantly associated with working memory. These results survived corrections for multiple comparisons. CONCLUSIONS: Our results demonstrated that NTSR1 SNP polymorphisms were significantly associated with variance in working memory performance among healthy adults. This result extended previous rodent studies showing that the NT deficiency impairs the working memory function. Future research should replicate our findings and extend to an examination of other dopamine modulators

    Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.

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    Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of ‘self-eating’ where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis

    Gestion de la qualité de l'eau, de la flore et de la faune : bilans et techniques de restauration

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    The analysis of the ecological impact of three types of artificial reservoirs shows that once the flows of a water streams are slowed, the animal diversity evolves towards limnophilous forms and changes in the potential fertility of the water stream, related to the nutrients supplied by the watershed and in some cases to a change in the bioavailability of sedimentary phosphorus, are observed. In order to limit the eutrophication process, control of the phosphorus supplied is absolutely necessary and this can require curative methods. But prior to that, a precise diagnosis and global analysis of the nuisances are necessary to the success of the restoration and management operations. / L'analyse de l'impact écologique de trois types de retenues artificielles montre que, dès que les eaux d'un fleuve sont ralenties, on observe, outre l'évolution de la diversité animale vers des formes limnophiles, la manifestation de la fertilité potentielle du cours d'eau, liée à la richesse des apports nutritifs du bassin versant et, dans certains cas, à la modification de la biodisponibilité du phosphore sédimentaire causée par les assecs. La prévention de l'accélération du processus d'eutrophisation passe en priorité par le contrôle des apports en phosphore et peut nécessiter la mise en oeuvre de méthodes curatives. Au préalable, un diagnostic précis et une analyse globale des nuisances perçues seront nécessaires au succès des opérations de restauration et de gestion

    Tribune libre sur le thème « Les feux de forêt dans les régions à climat méditerranéen ».

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    A l'issue de la table ronde internationale « Les feux de forêt dans les régions à climat méditerranéen » , orgnaisée par le Conservatoire du littoral, celui-ci a souhaité, afin de compléter les communications et synthèse, laisser libre cours aux idées de chacun. C'est ce dont rend compte cette tribune libre, qui était ouverte à l'ensemble des participants... huit d'entre eux y ont répondu

    Tribune libre sur le thème « Les feux de forêt dans les régions à climat méditerranéen ».

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    International audienceA l'issue de la table ronde internationale « Les feux de forêt dans les régions à climat méditerranéen » , orgnaisée par le Conservatoire du littoral, celui-ci a souhaité, afin de compléter les communications et synthèse, laisser libre cours aux idées de chacun. C'est ce dont rend compte cette tribune libre, qui était ouverte à l'ensemble des participants... huit d'entre eux y ont répondu
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