Morphological, physiological and behavioural evaluation of a ‘Mice in Space’ housing system

Environmental conditions likely affect physiology and behaviour of mice used for life sciences research on Earth or in Space. Here, we analysed the effects of cage confinement on the weightbearing musculoskeletal system, behaviour and stress of wild-type mice (C57BL/6JRj, 30 g b.wt., total n = 24) housed for 25 days in a prototypical ground-based and fully automated life support habitat device called “Mice in Space” (MIS). Compared with control housing (individually ventilated cages) the MIS mice revealed no significant changes in soleus muscle size and myofiber distribution (type I vs. II) and quality of bone (3-D microarchitecture and mineralisation of calvaria, spine and femur) determined by confocal and micro-computed tomography. Corticosterone metabolism measured non-invasively (faeces) monitored elevated adrenocortical activity at only start of the MIS cage confinement (day 1). Behavioural tests (i.e., grip strength, rotarod, L/D box, elevated plus-maze, open field, aggressiveness) performed subsequently revealed only minor changes in motor performance (MIS vs. controls). The MIS habitat will not, on its own, produce major effects that could confound interpretation of data induced by microgravity exposure during spaceflight. Our results may be even more helpful in developing multidisciplinary protocols with adequate scenarios addressing molecular to systems levels using mice of various genetic phenotypes in many laboratories

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The development of vestibular system and related functions in mammals: impact of gravity

International audienceThis chapter reviews the knowledge about the adaptation to Earth gravity during the development of mammals. The impact of early exposure to altered gravity is evaluated at the level of the functions related to the vestibular system, including postural control, homeostatic regulation, and spatial memory. The hypothesis of critical periods in the adaptation to gravity is discussed. Demonstrating a critical period requires removing the gravity stimulus during delimited time windows, what is impossible to do on Earth surface. The surgical destruction of the vestibular apparatus, and the use of mice strains with defective graviceptors have provided useful information on the consequences of missing gravity perception, and the possible compensatory mechanisms, but transitory suppression of the stimulus can only be operated during spatial flight. The rare studies on rat pups housed on board of space shuttle significantly contributed to this problem, but the use of hypergravity environment, produced by means of chronic centrifugation, is the only available tool when repeated experiments must be carried out on Earth. Even though hypergravity is sometimes considered as a mirror situation to microgravity, the two situations cannot be confused because a gravitational force is still present. The theoretical considerations that validate the paradigm of hypergravity to evaluate critical periods are discussed. The question of adaption of graviceptor is questioned from an evolutionary point of view. It is possible that graviception is hardwired, because life on Earth has evolved under the constant pressure of gravity. The rapid acquisition of motor programming by precocial mammals in minutes after birth is consistent with this hypothesis, but the slow development of motor skills in altricial species and the plasticity of vestibular perception in adults suggest that gravity experience is required for the tuning of graviceptors. The possible reasons for this dichotomy are discussed

L'orientation lointaine chez l'animal

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : TD 20567 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Etude de la locomotion chez deux lignées de souris consanguines (129/SV et C57BL/6J)

L'étude de la locomotion a été réalisée sur les deux lignées de souris consanguines : C57BL/6J et 129/Sv les plus utilisées en mutagenèse dirigée. Le but était triple 1) déterminer les caractéristiques de la locomotion chez la souris adulte, et l'évolution des capacités motrices avec l'âge ; 2) évaluer les effets de l'environnement sur l'activité motrice chez l'adulte, et au cours du développement précoce ; 3) évaluer l'effet du fond génétique sur les caractéristiques de la motricité. L'analyse comparative de la cinématique du mouvement sur les deux lignées a permis de montrer la relation entre la vitesse et la fréquence du pas, et l'existence d'une transition trot-galop à 70 cm/s. L'analyse de l'évolution de la motricité à différents âges a permis de montrer que, non seulement les deux lignées différent par leurs propriétés motrices, mais elles évoluent différemment en fonction de l'âge. L'étude des effets de l'environnement chez l'adulte a montré qu'un espace confiné perçu comme un environnement appauvri réduit l'activité motrice et change la typologie du muscle, alors qu'un espace confiné perçu comme un environnement enrichi augmente l'activité motrice et empêche l'atrophie musculaire. L'analyse des capacités motrices et du phénotype musculaire de souris soumises à différentes expériences motrices (environnement enrichi, entraînement sur tapis roulant, centrifugation chronique, suspension par la queue) durant la période de développement moteur a montré que l'expérience précoce change de façon durable les propriétés motrices. Cette analyse des effets à long terme de l'expérience précoce dans les deux lignées a validé l'hypothèse de période critique dans le développement moteur de la souris.A study of the mechanism of locomotion was carried out on the two inbred mice strains: C57BL/6J and 129/Sv mainly used to produce mutated mice line. The study aimed at 1) determining the characteristics of adult mouse locomotion, and age-related changes in the motricity; 2) evaluating the effects of the environment on the motor activity in adulhood mice, and during early development; 3) evaluating the effect of the genetic background on the motor characteristics. The comparative analysis of the kinematics allowed us to show the relationship between moving speed and step frequency, and a trot-gallop transition at 70 cm/s in mice. The analysis of the evolution of the motricity at differents ages showed that both strains have different motor skills, and a different evolution of motor properties with age. The study of the environmental effects on adult mice showed that a reduced and an impoverished environment decreases motor activity and modifies the muscle typology, while a reduced and an enriched environment increases motor activity and prevents muscle atrophy. The analysis of motor output and muscle phenotype of mice subjected to a different motor experience (enriched environment, forced exercise, chronique centrifugation, tail suspension) during their early motor development showed durable changes in their motor properties. The comparative analysis of the long term influence of early motor experience in the two strains validated the hypothesis of a critical period in the motor development of mice.AIX-MARSEILLE1-BU Sci.St Charles (130552104) / SudocSudocFranceF

Influence du champ gravitaire sur l'acquisition des capacités motrices chez la souris

L influence de la gravité sur le développement des capacités motrices a été étudiée chez la souris C57Bl/6J. Nous avons voulu savoir s il existait des périodes critiques dans l adaptation à la gravité. Nous avons utilisé pour cela l hypergravité par centrifugation chronique, seul moyen de modifier la pesanteur durant l embryogenèse des mammifères. Des groupes de souris ont été centrifugés (a) pendant le développement pré et périnatale (de la conception jusqu à l âge de 10 jours), (b) pendant le développement post-natal (du 10e jour au 30e) ou (c) sur l ensemble de ces deux périodes. Nous avons étudié, à l âge de 2 et 6 mois, (i) les mouvements compensateurs des yeux dans la stabilisation du regard par vidéo-oculographie et les réactions vestibulaires ; (ii) la dépense énergétiques par calorimétrie indirecte, et (iii) les paramètres cinématiques de la locomotion par vidéo-radiographie. Seules les souris centrifugées pendant l ensemble du développement présentent, au moins transitoirement, des réactions otolithiques perturbées. Ce résultat nous conduit à rejeter l hypothèse d une période critique vestibulaire, mais l observation de déficits dans certains tests de réactions vestibulaires des souris centrifugées à partir de P10 pourrait confirmer l hypothèse d une période critique dans l établissement des connexions vestibulo-cérébelleuses et vestibulo-spinales. L analyse du métabolisme a montré que seules les souris élevées prénatalement en hypergravité présentaient une dépense énergétique accrue à l âge de 2 et 6 mois. L analyse de la cinématique articulaire au cours de la locomotion a montré que l ajustement du contrôle postural a lieu, en partie, avant que les animaux ne commencent à marcher. En revanche, l ajustement des allures se fait après le 10e jours post-natal quand les animaux font l expérience de la marche. L ensemble de ces résultats démontrent l existence d une succession de périodes critiques dans l ontogenèse des capacités motrices.The influence of gravity on the development of motor skills was analysed on the mice C57Bl/6J. Our goal was to evaluate the hypothesis of critical periods in the adaptation to gravity. We used the chronic centrifugation that is the only available technique to modify the gravity during mammals embryogeny. Several groups of mice were centrifuged (a) during the early perinatal development (from conception to tenth postnatal day), (b) during the postnatal development (from day 10 to 30) or (c) during the whole periods. We analysed, at the age of 2 and 6 months, (i) the compensatory eye movements during the gaze stabilization by video-oculography, and the vestibular reactions; (ii) the energetic expanse by indirect calorimetry, and (iii) the kinematic parameters of locomotion by video-radiography. Only the mice centrifuged during their whole development showed at least transitory impairment of otolithic reactions. This result was inconsistent with a vestibular critical period, but the observation of impairments in some vestibular reactions of postnatally centrifuged mice could support the hypothesis of a critical period in the establishment of vestibulo-cerebellar or vestibulo-spinal connections. The metabolic analysis showed an increased energetic expense in mice exposed to hypergravity when 2 or 6 months old. The kinematic analysis of joints during locomotion showed that postural adjustment occurred, at least partly, before the mice started walking. On the other hand, the gait adjustment occured after tenth postnatal day, when the mice experiment walking. As a whole these results show the existence of several critical periods in the ontogenesis of motor capabilities.AIX-MARSEILLE2-Bib.electronique (130559901) / SudocSudocFranceF

Le développement précoce du contrôle moteur chez le rat nouveau-né

Les nouveau-nés des espèces nidicoles ont des performances motrices retardées par rapport aux espèces nidifuges. Ces performances réduites sont supposées refléter le caractère inachevé des structures impliquées dans la motricité. L\u27analyse du développement des structures neuronales, motrices et posturales montre que les éléments fondamentaux pour une motricité rudimentaire sont présents tôt après la naissance. Le développement plus tardif concerne des structures impliquées dans des comportements plus complexes. Les ratons montrent spontanément des comportements moteurs limités, mais révèlent des capacités motrices plus performantes dans des situations expérimentales particulières. On propose ici que les habilités motrices exprimées spontanément ne représentent pas les propriétés réelles des structures motrices, mais répondent plutôt à des comportements sélectionnés pour maintenir le raton dans le nid.Neonates of altricial species show reduced motor performances with reference to precocial species. Supposedly, their unachieved motor output mirrors the poorly matured underlying structures. Reviewing the developmental timetable of neural, motor and postural structures involved in rats\u27 walking shows that fundamental elements for a basic locomotion are present early after birth, whereas late developing structures are implied in complex behaviours. Whereas rat pups spontaneously show limited motor properties, they can reveal better motor capacities in particular behavioural situations. It is proposed that motor output spontaneously performed by pups does not mirror the actual properties of the motor structures, but results also from a selected behavioural mechanism whose function is to maintain the pups to the nest.</p

Postnatal training of 129/Sv mice confirms the long-term influence of early exercising on the motor properties of mice

International audienceA previous study showed that motor experiences during critical periods of development durably affect the motor properties of adult C57BL/6j mice. However, dependence on early environmental features may vary with the genetic profile. To evaluate the contribution of the genetic background on external influences to motricity, we performed the same experiment in a 129/Sv mouse strain that show a strongly different motor profile. Mice were subjected to endurance training (enriched environment or forced treadmill), hypergravity (chronic centrifugation), or simulated microgravity (hindlimb unloading) between postnatal days 10 and 30. They were then returned to standard housing until testing at the age of nine months. The endurance-trained mice showed a fast-slow shift in the deep zone of the tibialis. In addition, mice reared in the enriched environment showed a modified gait and body posture, and improved performance on the rotarod, whereas forced treadmill training did not affect motor output. Hypergravity induced a fast-slow shift in the superficial zone of the tibialis, with no consequence on motor output. Hindlimb unloading provoked an increased percentage of immature hybrid fibres in the tibialis and a shift in the soleus muscle. When compared with similarly reared C57BL/6j mice, 129/Sv mice showed qualitative differences attributable to the lower efficiency of early training due to their lower basal motor activity level. Nevertheless, the results are essentially consistent in both strains, and support the hypothesis that early motor experience influences the muscle phenotype and motor output. (C) 2016 Published by Elsevier B.V

Maternal behavior in mice: quantitative trait loci (QTL) mapping

36th Annual Meeting of the Behavior-Genetics-Association, Storrs, CT, JUN 24, 2006International audienceno abstrac