Hindlimb suspension in Wistar rats: Sex-based differences in muscle response

Ground-based animal models have been used extensively to understand the effects of microgravity on various physiological systems. Among them, hindlimb suspension (HLS), developed in 1979 in rats, remains the gold-standard and allows researchers to study the consequences of total unloading of the hind limbs while inducing a cephalic fluid shift. While this model has already brought valuable insights to space biology, few studies have directly compared functional decrements in the muscles of males and females during HLS. We exposed 28 adult Wistar rats (14 males and 14 females) to 14 days of HLS or normal loading (NL) to better assess how sex impacts disuse-induced muscle deconditioning. Females better maintained muscle function during HLS than males, as shown by a more moderate reduction in grip strength at 7 days (males: −37.5 ± 3.1%, females: −22.4 ± 6.5%, compared to baseline), that remains stable during the second week of unloading (males: −53.3 ± 5.7%, females: −22.4 ± 5.5%, compared to day 0) while the males exhibit a steady decrease over time (effect of sex × loading p = 0.0002, effect of sex × time × loading p = 0.0099). This was further supported by analyzing the force production in response to a tetanic stimulus. Further functional analyses using force production were also shown to correspond to sex differences in relative loss of muscle mass and CSA. Moreover, our functional data were supported by histomorphometric analyzes, and we highlighted differences in relative muscle loss and CSA. Specifically, female rats seem to experience a lesser muscle deconditioning during disuse than males thus emphasizing the need for more studies that will assess male and female animals concomitantly to develop tailored, effective countermeasures for all astronauts

Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model

For decades, scientists have relied on animals to understand the risks and consequences of space travel. Animals remain key to study the physiological alterations during spaceflight and provide crucial information about microgravity-induced changes. While spaceflights may appear common, they remain costly and, coupled with limited cargo areas, do not allow for large sample sizes onboard. In 1979, a model of hindlimb unloading (HU) was successfully created to mimic microgravity and has been used extensively since its creation. Four decades later, the first model of mouse partial weight-bearing (PWB) was developed, aiming at mimicking partial gravity environments. Return to the Lunar surface for astronauts is now imminent and prompted the need for an animal model closer to human physiology; hence in 2018, our laboratory created a new model of PWB for adult rats. In this review, we will focus on the rat model of PWB, from its conception to the current state of knowledge. Additionally, we will address how this new model, used in conjunction with HU, will help implement new paradigms allowing scientists to anticipate the physiological alterations and needs of astronauts. Finally, we will discuss the outstanding questions and future perspectives in space research and propose potential solutions using the rat PWB model

Ethers en C8 dérivés de polyéthylènes glycols, de l'isosorbide et du sorbitol (synthèse par télomérisation du butadiène et étude des propriétés amphiphiles)

Ce mémoire décrit la synthèse et l étude des propriétés physicochimiques d amphiphiles à base d éthylènes glycols, d isosorbide et de sorbitol. Dans un contexte de chimie verte, la télomérisation du butadiène, une réaction pallado-catalysée et industriellement viable, a été utilisée pour obtenir des éthers en chaines C8 insaturées. Elle permet d accéder à des amphiphiles non ioniques possédant une chaîne octadiényle dont les caractéristiques sont peu explorées dans la littérature. Ainsi, les propriétés physicochimiques des octadiényl et octyl éthers à base de tri- et tétra-éthylène glycol ont été comparées à l aide de la notion de HLD afin d évaluer l influence que peut avoir la présence des doubles liaisons sur ces propriétés. Ce manuscrit décrit une application de la réaction de télomérisation avec l isosorbide comme nucléophile. L isosorbide est un diol asymétrique issu de la biomasse végétale dont les éthers sont de bons candidats pour remplacer les éthers d éthylènes glycols courts reprotoxiques. La réaction de télomérisation avec ce substrat a donc été optimisée vers la production d espèces amphiphiles monoalkylés spécifiques en tenant compte de l asymétrie de la molécule. Le cas du sorbitol, un hexitol issu de l hydrogénation du glucose, a été envisagé dont les éthers sont difficilement accessibles au niveau industriel. Par conséquent, la télomérisation du sorbitol, suivie de l hydrogénation des produits, a permis d obtenir une fraction de monoéthers dont les performances, notamment en tant qu agent moussant, sont analogues voire supérieures à l octylglucoside, un alkyl glucoside 100% biodégradable.This paper describes the synthesis and physicochemical studies of amphiphiles based on ethylene glycol, isosorbide and sorbitol. Noteworthy in an actual context of green chemistry, the telomerization of butadiene, a pallado-catalyzed and industrially viable reaction, was used to obtain the corresponding unsaturated C8 ethers with a high atom-economy and smooth conditions. It provides access to non-ionic amphiphilic compounds with an octadienyl chain that can be hydrogenated to give the saturated derivatives. The physicochemical properties of octadienyl and octyl ethers based on tri-and tetra-ethylene glycol were compared using the HLD concept in order to determine the effects induced by the presence of unsaturations in the C8-chain on those properties. This manuscript describes an application of this reaction with isosorbide as nucleophile. Isosorbide is an asymmetric diol issuing from biomass. The corresponding ethers are good candidates to replace harmful short-ethers derived from ethylene glycols. The telomerization reaction with this substrate has been optimized to produce amphiphilic monoalkylated species, taking into account the asymmetry of the molecule. The synthesis challenge has been issued in the case of sorbitol, a hexitol obtained from the hydrogenation of glucose. Ethers derived from sorbitol are currently not easily accessible at the industrial scale. By hydrogenation of the products of telomerization, a fraction of pure saturated monoethers has been synthesized at the laboratory scale. The performances of this product, especially as foaming agent, are similar or even better than the ones of octylglucoside, a 100 % biodegradable alkyl glucoside.LILLE1-Bib. Electronique (590099901) / SudocSudocFranceF

Hydrosilylation asymétrique de cétones fonctionnalisées avec le PMHS (utilisation de complexes de zinc)

L'hydrosilylation asymétrique est une voies d'accès aux alcools et amines énantiopurs. Bien que très efficace, le coût et la toxicité des réducteurs silanes associés limite son application industrielle. Notre étude a porté sur le développement d'un système catalytique associant le zinc à des diamines et utilisant le PMHS, hydrosilane peu cher, stable et nontoxique. En milieu aprotique, la réduction d'alkylarylcétones s'effectue avec de hautes cbimio- et énantiosélectivités. La synthèse de nouvelles 1,2-diamines a permis d'atteindre 91 % d'excès énantiomérique sur l'acétophénone. Les substrats polyfonctionnels sont cependant difficilement réduits dans le toluène. A l'opposée, ce système est efficace en milieu protique sur une large gamme de substrats (alkylarylcétones, a- et b-cétoesters, cétoamides et imines). La procédure de réduction simple en une étape mène à d'excellentes activités et chimiosélectivités, les énantiosélectivités restant toutefois modestes (15-48 %). Divers précurseurs catalytiques simples et peu chers, tels que Zn(OMe)2ou Zn(OH)2,peuvent être employés. L'étude des mécanismes en milieu aprotique/protique a conduit à la synthèse et à l'étude de la réactivité de nouveaux complexes de zinc, proposés comme intermédiaires réactionnels ) pour expliquer les réactivités inhabituelles en milieu protique.LILLE1-BU (590092102) / SudocSudocFranceF

Electrical impedance myography for the detection of muscle inflammation induced by λ-carrageenan.

Electrical impedance myography (EIM) is a technique for the assessment of muscle health and composition and has been shown to be sensitive to a variety of muscle pathologies including neurogenic atrophy and connective tissue deposition. However, it has been minimally studied in pure inflammation. In this study, we sought to assess EIM sensitivity to experimental inflammation induced by the localized intramuscular injection of λ-carrageenan. A total of 91 mice underwent 1-1000 kHz EIM measurements of gastrocnemius using a needle array, followed by injection of either 0.3% λ-carrageenan in phosphate-buffered saline (PBS) or PBS alone. Animals were then remeasured with EIM at 4, 24, 48, or 72 hours and euthanized and quantitative assessment of muscle histology was performed. Parallel alterations in both 5 and 50 kHz EIM values were identified at 4 and 24 hours, including reductions in phase, reactance, and resistance. In PBS-treated animals these values normalized by 48 hours, whereas substantial reductions in phase and reactance in 5 kHz EIM values persisted at 48 and 72 hours (i.e., values of phase 72 hours post-injection were 6.51 ± 0.40 degrees for λ-carrageenan versus 8.44 ± 0.35 degrees for PBS p<0.001, n = 11 per group). The degree of basophilic area observed in muscle sections by histology correlated to the degree of phase change at these two time points (Rspearman = -0.51, p = 0.0029). Changes in low frequency EIM parameters are sensitive to the presence of inflammatory infiltrates, and have the potential of serving as a simple means of quantifying the presence and extent of muscle inflammation without the need for biopsy