Vieillissement et rythmes biologiques chez les primates

Les rythmes biologiques constituent un avantage adaptatif puisqu’ils permettent d’harmoniser les rapports entre l’organisme et les variations cycliques de l’environnement. Avec l’âge, apparaissent des perturbations rythmiques caractérisées, le plus souvent, par des baisses d’amplitude et des décalages de phase. Hormis l’homme, les recherches sur les primates restent encore fragmentaires. Néanmoins, les données actuelles suggèrent que l’affaiblissement rythmique de l’organisme vieillissant procèderait d’un dysfonctionnement des noyaux suprachiasmatiques. Ces noyaux présentent des oscillations endogènes entraînées par la lumière et, avec l’âge, les capacités de réponses à la lumière seraient diminuées, se traduisant par une désynchronisation interne. La connaissance précise des altérations rythmiques liées à l’âge devrait suggérer, à terme, des traitements assurant le maintien ou la restauration de rythmes biologiques chez l’homme vieillissant, gage d’une meilleure qualité de vie et même de survie.All living organisms exhibit rhythmic activities in a wide variety of endocrine and behavioural parameters. These biological rhythms are endogenously generated by a circadian clock, and they are entrained by cyclic variations of environmental factors called synchronizers. Aging is associated with changes in amplitude and temporal organization of many daily and seasonal rhythms. In humans, daily rhythms of sleep, thermoregulation and hormonal secretion are severely altered with aging. Except in humans, studies on primates are scarce. However, age-related effects on biological rhythms are relatively consistent among primate species studied to date, including humans. Therefore, non human primates are of valuable use for such investigations. Most studies have been performed on the Rhesus macaque (longevity 35-40 years) and on the gray mouse lemur (longevity 10-12 years). Like in humans, the rest-activity rhythm becomes fragmented in aged primates, and shows an increased activity during the resting period. Aging induces a decrease in amplitude of the body temperature rhythm and an increase in energy consumption. Various hormonal secretions exhibit a decrease with aging, but the rhythmic components of these declines have not always been depicted. Moreover, changes (amplitude or phase) in daily variations depended of the hormonal secretion tested. Taken together, these results suggest that the biological clock in the brain would be a primary target of aging. The main central clock is located in the suprachiasmatic nucleus of the hypothalamus whose endogenous oscillations are entrained by light. In this brain structure, cellular function and sensitivity to light show drastic changes with age in the mouse lemur. The precise knowledge of age-related alterations of biological rhythms in primates can have important consequences on the development of new treatments to maintain or restore biological rhythmicity in the elderly

Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity

<p>Abstract</p> <p>Background</p> <p>Resveratrol, a natural polyphenolic compound, was shown to protect rodents against high-fat-diet induced diabesity by boosting energy metabolism. To the best of our knowledge, no data is yet available on the effects of resveratrol in non-human primates. Six non-human heterotherm primates (grey mouse lemurs, <it>Microcebus murinus</it>) were studied during four weeks of dietary supplementation with resveratrol (200 mg/kg/day) during their winter body-mass gain period. Body mass, spontaneous energy intake, resting metabolic rate, spontaneous locomotor activity and daily variations in body temperature were measured. In addition, the plasma levels of several gut hormones involved in satiety control were evaluated.</p> <p>Results</p> <p>Resveratrol reduced the seasonal body-mass gain by concomitantly decreasing energy intake by 13% and increasing resting metabolic rate by 29%. Resveratrol supplementation inhibited the depth of daily torpor, an important energy-saving process in this primate. The daily amount of locomotor activity remained unchanged. Except for an increase in the glucose-dependent insulinotropic polypeptide, a gut hormone known to promote mobilization of fat stores, no major change in satiety hormone plasma levels was observed under resveratrol supplementation.</p> <p>Conclusions</p> <p>These results suggest that in a non-human primate, resveratrol reduces body-mass gain by increasing satiety and resting metabolic rate, and by inhibiting torpor expression. The measured anorectic gut hormones did not seem to play a major role in these observations.</p

Condition corporelle et grégarisme diurne chez des mâles Microcèbes (Microcebus murinus) en saison de reproduction

In the Gray Mouse Lemur, a nocturnal Malagasy primate, nest sharing during the diurnal sleeping period provides significant thermoregulatory advantages. Using socially housed captive male mouse lemurs, we tested the hypothesis that males would present differential physiological parameters depending on their nest sharing patterns at the beginning of the breeding season. Nest composition, and health status inferred from body weight, reproductive activity (testis width) and level of immune activity (lymphocyte number) were recorded at the beginning of the breeding season and after 4 weeks in newly formed 4 groups of 5 adult males. One nest was occupied by 3 males or more in 85 % of the surveys, and 14 cases of males found alone in a nest were recorded, distributed over 65 % of the surveys. Males found alone or in pairs lost significantly more weight after the 4 weeks of social grouping than males found in groups of 3 or more individuals in a nest. Additionally, males expelled from common nests had reduced immune activity prior to social grouping than nest associated males. Nest associated males had little change in their lymphocyte numbers after the 4 weeks of social grouping, whereas isolated males exhibited a pronounced increase in lymphocyte numbers. These results indicate that, in mouse lemurs, nest-sharing pattern at the beginning of the breeding season is a complex process, yielding diverse energetic and immunological consequencesChez un primate prosimien malgache nocturne, le regroupement dans des gîtes pendant la période de sommeil diurne représente un avantage énergétique certain. Sur des mâles microcèbes captifs maintenus en groupes sociaux, nous avons testé l'hypothèse que les mâles présenteraient des paramètres physiologiques différents en fonction de leur patron de regroupement dans les gîtes au début de la saison de reproduction. La composition des gîtes, l'état de santé à travers le poids corporel, la fonction de reproduction (taille des testicules) et le niveau du système immunitaire (nombre de lymphocytes) ont été suivis au début de la période de reproduction et après 4 semaines sur 4 groupes sociaux nouvellement formés de 5 mâles chacun. Un seul gîte était occupé par 3 mâles ou plus dans 85 % des cas, et 14 cas de mâles isolés dans un gîte furent enregistrés, répartis sur 65 % des observations. Les mâles trouvés isolés ou par paires ont perdu significativement plus de poids sur les 4 semaines de suivi que les mâles regroupés par 3 ou plus dans un gîte. En outre, les mâles rejetés des nichoirs communs présentaient un système immunitaire moins bon avant la mise en groupe sociaux par rapport aux mâles regroupés dans les nids. Cependant, aucune évolution significative n'a été observée au cours des 4 semaines chez les microcèbes regroupés dans les gîtes, alors que les mâles isolés ont montré une augmentation significative de leur nombre de lymphocytes. Ces résultats indiquent que, chez le Microcèbe, le regroupement dans les gîtes diurnes pendant la période d'activation sexuelle est un processus complexe, impliquant différentes conséquences énergétiques et immunitaires

Impaired Control of Body Cooling during Heterothermia Represents the Major Energetic Constraint in an Aging Non-Human Primate Exposed to Cold

Daily heterothermia is used by small mammals for energy and water savings, and seems to be preferentially exhibited during winter rather than during summer. This feature induces a trade-off between the energy saved during daily heterothermia and the energy cost of arousal, which can impact energy balance and survival under harsh environmental conditions. Especially, aging may significantly affect such trade off during cold-induced energy stress, but direct evidences are still lacking. We hypothesized that aging could alter the energetics of daily heterothermia, and that the effects could differ according to season. In the gray mouse lemur (Microcebus murinus), a non-human primate species which exhibits daily heterothermia, we investigated the effects of exposures to 25 and 12°C on body composition, energy balance, patterns of heterothermia and water turnover in adult (N = 8) and aged animals (N = 7) acclimated to winter-like or summer-like photoperiods

An Adaptive Building Skin Concept Resulting from a New Bioinspiration Process: Design, Prototyping, and Characterization

Building envelopes can manage light, heat gains or losses, and ventilation and, as such, play a key role in the overall building performance. Research has been focusing on increasing their efficiency by proposing dynamic and adaptive systems, meaning that they evolve to best meet the internal and external varying conditions. Living organisms are relevant examples of adaptability as they have evolved, facing extreme conditions while maintaining stable internal conditions for survival. From a framework based on the inspiration of living envelopes such as animal constructions or biological skins, the concept of an adaptive envelope inspired by the Morpho butterfly was proposed. The system can manage heat, air, and light transfers going through the building and includes adaptive elements with absorption coefficients varying with temperature. This paper presents the developed framework that led to the final concept as well as the concept implementation and assessment. A prototype for heat and light management was built and integrated into a test bench. Measurements were performed to provide a first assessment of the system. In parallel, geometrical parametric models were created to compare multiple configurations in regards to indicators such as air, light, or heat transfers. One of the models provided light projections on the system that were compared with measurements and validated as suitable inputs in grey-box models for the system characterization

On-going frontal alpha rhythms are dominant in passive state and desynchronize in active state in adult gray mouse lemurs

The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org), we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8-12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographic (EMG; bipolar electrodes sutured in neck muscles) data were recorded in 13 male adult (about 3 years) lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity) and awake passive state (no sleep) were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7-9 Hz) during passive state. During active state, there was a reduction in alpha power density (8-12 Hz) and an increase of power density at slow frequencies (1-4 Hz). Relative EMG activity was related to EEG power density at 2-4 Hz (positive correlation) and at 8-12 Hz (negative correlation). These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science) and applied (pharmacological and non-pharmacological interventions) research in Neurophysiology

Orientation preference maps in Microcebus murinus reveal size-invariant design principles in primate visual cortex

Orientation preference maps (OPMs) are a prominent feature of primary visual cortex (V1) organization in many primates and carnivores. In rodents, neurons are not organized in OPMs but are instead interspersed in a ‘‘salt and pepper’’ fashion, although clusters of orientation-selective neurons have been reported. Does this fundamental difference reflect the existence of a lower size limit for orientation columns (OCs) below which they cannot be scaled down with decreasing V1 size? To address this question, we examined V1 of one of the smallest living primates, the 60-g prosimian mouse lemur (Microcebus murinus). Using chronic intrinsic signal imaging, we found that mouse lemur V1 contains robust OCs, which are arranged in a pinwheel-like fashion. OC size in mouse lemurs was found to be only marginally smaller compared to the macaque, suggesting that these circuit elements are nearly incompressible. The spatial arrangement of pinwheels is well described by a common mathematical design of primate V1 circuit organization. In order to accommodate OPMs, we found that the mouse lemur V1 covers one-fifth of the cortical surface, which is one of the largest V1-to-cortex ratios found in primates. These results indicate that the primate-type visual cortical circuit organization is constrained by a size limitation and raises the possibility that its emergence might have evolved by disruptive innovation rather than gradual change

Design processes and multi-regulation of biomimetic building skins: A comparative analysis

Biomimetics is an opportunity for the development of energy efficient building systems. Several biomimetic building skins (Bio-BS) have been built over the past decade, however few addressed multi-regulation although the biological systems they are inspired by have multi-functional properties. Recent studies have suggested that despite numerous tools and methods described in the literature for the development of biomimetic systems, their use for designing Bio-BS is scarce. To assess the main challenges of biomimetic design processes and their influence on the final design, this paper presents a comparative analysis of several existing Bio-BS. The analyses were carried out with univariable and multivariate descriptive tools in order to highlight the main trends, similarities and differences between the projects. The authors evaluated the design process of thirty existing Bio-BS, including a focus on the steps related to the understanding of the biological models. Data was collected throughout interviews. The univariate analysis revealed that very little Bio-BS followed a biomimetic design framework (5%). None of the Bio-BS was as multi-functional as their biological model(s) of inspiration. A further conclusion drawn that Bio-BS are mostly inspired by single biological organisms (82%), which mostly belong to the kingdom of animals (53%) and plants (37%). The multivariate analysis outlined that the Bio-BS were distributed into two main groups: (1) academic projects which present a strong correlation with the inputs in biology in their design processes and resulted in radical innovation; (2) public building projects which used conventional design and construction methods for incremental innovation by improving existing building systems. These projects did not involve biologists neither a thorough understanding of biological models during their design process. Since some biomimetic tools are available and Bio-BS have shown limitations in terms of multifunctionality, there is a need to promote the use of multidisciplinary tools in the design process of Bio-BS, and address the needs of the designers to enhance the application of multi-regulation capabilities for improved performances

Encephalopathy induced by Alzheimer brain inoculation in a non-human primate.

Alzheimer's disease is characterized by cognitive alterations, cerebral atrophy and neuropathological lesions including neuronal loss, accumulation of misfolded and aggregated β-amyloid peptides (Aβ) and tau proteins. Iatrogenic induction of Aβ is suspected in patients exposed to pituitary-derived hormones, dural grafts, or surgical instruments, presumably contaminated with Aβ. Induction of Aβ and tau lesions has been demonstrated in transgenic mice after contamination with Alzheimer's disease brain homogenates, with very limited functional consequences. Unlike rodents, primates naturally express Aβ or tau under normal conditions and attempts to transmit Alzheimer pathology to primates have been made for decades. However, none of earlier studies performed any detailed functional assessments. For the first time we demonstrate long term memory and learning impairments in a non-human primate (Microcebus murinus) following intracerebral injections with Alzheimer human brain extracts. Animals inoculated with Alzheimer brain homogenates displayed progressive cognitive impairments (clinical tests assessing cognitive and motor functions), modifications of neuronal activity (detected by electroencephalography), widespread and progressive cerebral atrophy (in vivo MRI assessing cerebral volume loss using automated voxel-based analysis), neuronal loss in the hippocampus and entorhinal cortex (post mortem stereology). They displayed parenchymal and vascular Aβ depositions and tau lesions for some of them, in regions close to the inoculation sites. Although these lesions were sparse, they were never detected in control animals. Tau-positive animals had the lowest performances in a memory task and displayed the greatest neuronal loss. Our study is timely and important as it is the first one to highlight neuronal and clinical dysfunction following inoculation of Alzheimer's disease brain homogenates in a primate. Clinical signs in a chronic disease such as Alzheimer take a long time to be detectable. Documentation of clinical deterioration and/or dysfunction following intracerebral inoculations with Alzheimer human brain extracts could lead to important new insights about Alzheimer initiation processes

Deficits of psychomotor and mnesic functions across aging in mouse lemur primates.

Owing to a similar cerebral neuro-anatomy, non-human primates are viewed as the most valid models for understanding cognitive deficits. This study evaluated psychomotor and mnesic functions of 41 young to old mouse lemurs (Microcebus murinus). Psychomotor capacities and anxiety-related behaviors decreased abruptly from middle to late adulthood. However, mnesic functions were not affected in the same way with increasing age. While results of the spontaneous alternation task point to a progressive and widespread age-related decline of spatial working memory, both spatial reference and novel object recognition (NOR) memory tasks did not reveal any tendency due to large inter-individual variability in the middle-aged and old animals. Indeed, some of the aged animals performed as well as younger ones, whereas some others had bad performances in the Barnes maze and in the object recognition test. Hierarchical cluster analysis revealed that declarative-like memory was strongly impaired only in 7 out of 25 middle-aged/old animals. These results suggest that this analysis allows to distinguish elder populations of good and bad performers in this non-human primate model and to closely compare this to human aging.journal article20142015 01 09importe