•Fish hydrolysate contains n-3 LC-PUFAs and low molecular weight peptides.•Fish hydrolysate prevents age-related short-term memory deficits.•Fish hydrolysate affects navigation strategies during ...spatial learning.•Fish hydrolysate possesses immunomodulatory and anxiolytic properties.•Fish hydrolysate is promising for the prevention of age-related cognitive decline.
Brain aging is characterized by a decline in cognitive functions, which can lead to the development of neurodegenerative pathologies. Age-related spatial learning and memory deficits are associated with a chronic low-grade inflammation. Anxiety disorders and stress response alterations, occurring for a part of the elderly, have also been linked to an increased neuroinflammation and thus, an accelerated cognitive decline. Nutrition is an innovative strategy to prevent age-related cognitive impairments. Among the nutrients, n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides from proteins, especially those from marine resources, are good candidates for their immunomodulatory, anxiolytic and neuroprotective properties. The aim of this study is to determine the combined effect of n-3 LC-PUFAs and low molecular weight peptides on cognitive functions, and their mechanism of action. We are the first to show that a dietary supplementation with a fish hydrolysate containing n-3 LC-PUFAs and low molecular weight peptides prevented the age-related spatial short-term memory deficits and modulated navigation strategies adopted during spatial learning. In addition, the fish hydrolysate displayed anxiolytic activities with the reduction of anxiety-like behaviour in aged mice, restored the plasmatic corticosterone levels similar to adult animals following an acute stress and modulated the hypothalamic stress response. These effects on behaviour can be explained by the immunomodulatory and neuroprotective properties of the fish hydrolysate that limited microgliosis in vivo, decreased LPS-induced expression of pro-inflammatory cytokines and increased the expression of growth factors such as BDNF and NGF in vitro. Thus, n-3 LC-PUFAs and low molecular weight peptides contained in the fish hydrolysate can play an important role in the limitation of neuroinflammation and stress response alterations during aging and represent a potential strategy for the prevention of age-related cognitive decline.
La neuroinflammation représente un mécanisme de défense crucial du système nerveux central contre les agents pathogènes afin d’assurer un retour à l’homéostasie dans le cerveau. Cette réponse ...immunitaire physiologique est orchestrée par les cellules microgliales, les cellules du système immunitaire cérébral. Cependant, une production soutenue et incontrôlée des facteurs pro-inflammatoires associée à une activation microgliale ainsi qu’une dérégulation de la résolution de l’inflammation contribuent à l’apparition d’une inflammation chronique à bas bruit, comme observé au cours du vieillissement et dans les maladies neurodégénératives, pouvant entraîner des lésions neuronales responsables, en partie, des troubles cognitifs. La nutrition apparaît comme une stratégie innovante pour prévenir les altérations liées à la neuroinflammation. Les acides gras polyinsaturés n-3 (AGPI n-3) à longue chaîne et les peptides de petits poids moléculaires sont de bons candidats en raison de leurs propriétés immunomodulatrices et pro-résolutives via la production d’oxylipines. L’objectif de cette étude est d’évaluer le potentiel anti-inflammatoire du Mnemosyss®, un hydrolysat de coproduits marins combinant ces composés, sur l’inflammation aiguë et de comparer cet effet à une supplémentation en DHA seul.
Des souris âgées de 7 semaines ont été supplémentées pendant 18jours avec du Mnemosyss®, du DHA ou une solution contrôle. L’inflammation aiguë a été induite par une injection intrapéritonéale de lipopolysaccharide (LPS) et les souris ont été euthanasiées 2h après. Les analyses ont été effectuées dans l’hippocampe. L’expression des marqueurs inflammatoires, des marqueurs d’activation microgliale a été mesurée par RT-qPCR. L’expression protéique de IκB et de NF-κB a été quantifiée par Western-Blot. Enfin, la composition en oxylipines a été évaluée par chromatographie liquide couplée à la spectrométrie de masse.
En réponse au LPS, la supplémentation en Mnemosyss® diminue l’expression des cytokines pro-inflammatoires IL-6 (p<0,001), IL-1β (p<0,001) et TNF-α (p<0,01) alors que le DHA réduit uniquement l’expression de l’IL-6 (p<0,01). Cette baisse de l’expression des cytokines pro-inflammatoires est associée à une augmentation de l’expression protéique de IκB (p<0,05 et p<0,01 vs. DHA et contrôle, respectivement) et à une modulation des marqueurs d’activation microgliale dans l’hippocampe. Les effets du Mnemosyss® pourraient être dus, en partie, au changement du profil en oxylipines vers un profil plus anti-inflammatoire par rapport à la supplémentation en DHA.
Cette étude démontre le pouvoir anti-inflammatoire et pro-résolutif du Mnemosyss®. Celui-ci est même plus efficace que le DHA seul pourtant apporté en plus grande quantité suggérant un effet des peptides seuls ou une potentialisation du DHA par les peptides. Il pourrait donc être proposé pour freiner l’inflammation au cours du vieillissement ou lors de pathologies inflammatoires aiguës ou chroniques.
Neuroinflammation constitutes a normal part of the brain immune response orchestrated by microglial cells. However, a sustained and uncontrolled production of proinflammatory factors together with ...microglial activation contribute to the onset of a chronic low-grade inflammation, leading to neuronal damage and cognitive as well as behavioral impairments. Hence, limiting brain inflammatory response and improving the resolution of inflammation could be particularly of interest to prevent these alterations. Dietary n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides are good candidates because of their immunomodulatory and proresolutive properties. These compounds are present in a fish hydrolysate derived from marine-derived byproducts. In this study, we compared the effect of an 18-day supplementation with this fish hydrolysate to a supplementation with docosahexaenoic acid (DHA) on lipopolysaccharide (LPS)-induced inflammation in mice. In response to peripherally injected LPS, the fish hydrolysate supplementation decreased the hippocampal mRNA expression of the proinflammatory cytokines IL-6 (
< 0.001), IL-1β (
= 0.0008) and TNF-α (
< 0.0001), whereas the DHA supplementation reduced only the expression of IL-6 (
= 0.004). This decline in proinflammatory cytokine expressions was associated with an increase in the protein expression of IκB (
= 0.014 and
= 0.0054 as compared to the DHA supplementation and control groups, respectively) and to a modulation of microglial activation markers in the hippocampus. The beneficial effects of the fish hydrolysate could be due in part to the switch of the hippocampal oxylipin profile towards a more anti-inflammatory profile as compared to the DHA supplementation. Thus, the valorization of fish byproducts seems very attractive to prevent and counteract neuroinflammation.
Rydberg atoms are remarkable tools for quantum simulation and computation. They are the focus of an intense experimental activity, mainly based on low-angular-momentum Rydberg states. Unfortunately, ...atomic motion and levels lifetime limit the experimental timescale to about 100 μs. Here, we demonstrate two-dimensional laser trapping of long-lived circular Rydberg states for up to 10 ms. Our method is very general and opens many opportunities for quantum technologies with Rydberg atoms. The 10 ms trapping time corresponds to thousands of interaction cycles in a circular-state-based quantum simulator. It is also promising for quantum metrology and quantum information with Rydberg atoms, by bringing atom-field interaction times into unprecedented regimes.
Brain aging is characterized by a chronic low-grade inflammation, which significantly impairs cognitive function. Microglial cells, the immunocompetent cells of the brain, present a different ...phenotype, switching from a homeostatic signature (M0) to a more reactive phenotype called “MGnD” (microglial neurodegenerative phenotype), leading to a high production of pro-inflammatory cytokines. Furthermore, microglial cells can be activated by age-induced gut dysbiosis through the vagus nerve or the modulation of the peripheral immune system. Nutrients, in particular n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides, display powerful immunomodulatory properties, and can thus prevent age-related cognitive decline. The objective of this study was to investigate the effects of n-3 LC-PUFAs and low molecular weight peptides contained in a marine by-product-derived hydrolysate on microglial phenotypes and intestinal permeability and their consequences on cognition in mice. We demonstrated that the hydrolysate supplementation for 8 weeks prevented short- and long-term memory decline during aging. These observations were linked to the modulation of microglial signature. Indeed, the hydrolysate supplementation promoted homeostatic microglial phenotype by increasing TGF-β1 expression and stimulated phagocytosis by increasing Clec7a expression. Moreover, the hydrolysate supplementation promoted anti-inflammatory intestinal pathway and tended to prevent intestinal permeability alteration occurring during aging. Therefore, the fish hydrolysate appears as an interesting candidate to prevent cognitive decline during aging.
Rydberg atoms are remarkable tools for the quantum simulation of spin arrays. Circular Rydberg atoms open the way to simulations over very long time scales, using a combination of laser trapping of ...the atoms and spontaneous-emission inhibition, as shown in the proposal of a XXZ spin-array simulator based on chains of trapped circular atoms T.L. Nguyen $\textit{et al.}$, Phys. Rev. X 8, 011032 (2018). Such simulators could reach regimes (thermalization, glassy dynamics) that are out of the reach of those based on ordinary, low-angular-momentum short-lived Rydberg atoms. Over the promised long time scales, the unavoidable coupling of the spin dynamics with the atomic motion in the traps may play an important role. We study here the interplay between the spin exchange and motional dynamics in the simple case of two interacting circular Rydberg atoms confined in harmonic traps. The time evolution is solved exactly when the position dependence of the dipole-dipole interaction terms can be linearized over the extension of the atomic motion. We present numerical simulations in more complex cases, using the realistic parameters of the simulator proposal. We discuss three applications. First, we show that realistic experimental parameters lead to a regime in which atomic and spin dynamics become fully entangled, generating interesting non-classical motional states. We also show that, in other parameter regions, the spin dynamics notably depends on the initial temperature of the atoms in the trap, providing a sensitive motional thermometry method. Last, and most importantly, we discuss the range of parameters in which the motion has negligible influence over the spin dynamics.
The exquisite properties of Rydberg levels make them particularly appealing for emerging quantum technologies. The lifetime of low-angular-momentum laser-accessible levels is however limited to a few ...100μs by optical transitions and microwave blackbody radiation (BBR) induced transfers at room temperature. A considerable improvement would be obtained with the few 10ms lifetime of circular Rydberg levels in a cryogenic environment reducing the BBR temperature. We demonstrate the preparation of long-lived circular Rydberg levels of laser-cooled rubidium atoms in a cryostat. We observe a 3.7ms lifetime for the circular level of principal quantum number n=52. By monitoring the transfers between adjacent circular levels, we estimate in situ the microwave BBR temperature to be (11±2)K. The measured atomic coherence time (270μs) is limited here only by technical magnetic field fluctuations. This work opens interesting perspectives for quantum simulation and sensing with cold circular Rydberg atoms.
Le centre de la terre Wynands, Marie-Pierre; Méhaignerie, P.; Deneux, M.
Études rurales,
07/2019
204
Journal Article
Recenzirano
Cet article porte sur l’étude croisée de la trajectoire de professionnalisation et de « notabilisation » de deux démocrates-chrétiens (Marcel Deneux et Pierre Méhaignerie) ainsi que de leur ...inscription dans un champ de relations en milieu rural. Elle montre que ces deux personnalités politiques, loin de ne devoir à la démocratie chrétienne qu’une lointaine filiation idéologique, sont avant tout des élus au sein d’un vaste réseau rural, travaillé par l’action socialisatrice de l’Église catholique et orienté vers leur réussite. Ce réseau rend compte des conditions de leur entrée « en politique » ainsi que des logiques sociales de l’inévitable prise de distance vis-à-vis d’un étiquetage démocrate-chrétien de telles activités.
This article offers a comparative study of the paths leading to the professionalisation and prominence of two Christian democrats, Marcel Deneux and Pierre Méhaignerie, and their integration into important circles in rural areas. It shows that these two political figures, far from having only distant ideological connections with Christian democracy, are above all elected officials within a vast rural network developed through the socialising actions of the Catholic Church and dedicated to their success. This network helps to explain the conditions of their entry into politics and the social rationale for why they inevitably distanced their activities from the Christian democrat label.
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