Abstract Emotions are omnipresent in many animals' lives. It is a complex concept that encompasses physiological, subjective, behavioural and cognitive aspects. While the complex relationship between ...emotion and cognition has been well studied in humans and in some nonhuman primates, it remains rather unexplored for other nonhuman primate species, such as lemurs. In our study, we evaluated the performance of N = 48 grey mouse lemurs ( Microcebus murinus ) in a discrimination learning task using visual emotional stimuli. We tested whether the type of visual stimulus (positive, negative or neutral) influenced the cognitive performance of mouse lemurs. Individuals had to learn to discriminate between two platforms according to the associated visual stimuli and to jump to the target platform (leading to a reward). Our main finding was that emotional stimuli, whether positive or negative in valence, impaired cognitive performance when used as a target. Specifically, the lowest success rate occurred when the target was associated with the emotional stimuli, and the highest success rate occurred when it was associated with neutral stimuli. Our results show a similar pattern to that found in other primate species and support the adaptive role of emotion. Our results also support that individual differences could be a factor impacting the relation between emotion and cognition. This study is the first to explore how emotions interfere with the cognitive abilities of a lemur species and highlights the importance of acknowledging emotion in mouse lemurs as well as studying the emotion‐cognition interaction in a wider range of primate species.
Research Highlights Influence of emotion on cognition has never been studied on lemuriforms. The emotional value of visual stimuli impacted cognitive performance of mouse lemurs. It is crucial to account for mouse lemurs' emotions and study the emotion cognition interaction in a wider range of primate species.
Cognitive decline in the elderly, particularly Alzheimer’s disease (AD), is a major socio-economic and healthcare concern. We review here the literature on one specific aspect of diet affecting AD, ...that of the ω3 fatty acids, particularly the brain’s principle ω3 fatty acid – docosahexaenoic acid (DHA). DHA has deservedly received wide attention as a nutrient supporting both optimal brain development and for cardiovascular health. Our aim here is to critically assess the quality of the present literature as well as the potential of ω3 fatty acids to treat or delay the onset of AD. We start with a brief description of cognitive decline in the elderly, followed by an overview of well recognized biological functions of DHA. We then turn to epidemiological studies, which are largely supportive of protective effects of fish and DHA against risk of AD. However, biological studies, including blood and brain DHA analyses need careful interpretation and further investigation, without which the success of clinical trials with DHA may continue to struggle. We draw attention to some of the methodological issues that need resolution as well as an emerging mechanism that may explain how DHA could be linked to protecting brain function in the elderly.
MicroRNA (miRNA) are endogenous small noncoding RNA gene products, on average 22 nt long, that play important regulatory roles in mediating gene expression by binding to and targeting mRNAs for ...degradation or translational repression. In this paper we identify both novel and conserved miRNA sequences present in the genome of the gray mouse lemur, Microcebus marinus. In total, 122 conserved and 44 novel miRNA were identified with high confidence from the lemur genome (Mmur_2.0) and were used for expression analysis. All conserved and novel miRNA were subjected to relative quantification by RT-qPCR in liver samples from control and torpid lemurs. A total of 26 miRNA (16 conserved and 10 novel) showed increased levels during primate torpor, whereas 31 (30 conserved and 1 novel) decreased. Additional in silico mapping of the predicted mRNA targets of torpor-responsive mature miRNA suggested that miRNA that increased during torpor were collectively involved in cell development and survival pathways, while miRNA that decreased were enriched in targeting immune function. Overall, the study suggests new regulatory mechanisms of primate torpor via miRNA action.
•Characterization of torpor-responsive miRNA expression from the Gray mouse lemur•Identification of novel torpor-responsive lemur miRNA•In silico prediction of torpor-responsive miRNA targets and cellular function in coordinating primate torpor
•Caloric restriction lowers learning abilities.•Individuals losing the more weight are the one performing poorly in a discrimination task.•Learning abilities are affected during caloric restriction ...while previously acquired memory is not.
Brain functions are known to consume high levels of energy, thus, the integrity of cognitive performance can be drastically impacted by acute caloric restriction. In this study, we tested the impact of a 40% caloric restriction on the cognitive abilities of the grey mouse lemur (Microcebus murinus).
Twenty-three male mouse lemurs were divided into two groups: 13 control animals (CTL) that were fed with 105kJ/day and 10calorie restricted (CR) animals that received 40% less food (63kJ/day) than the CTL animals. The animals were fed according to their group for 19days. Before treatment, we assessed baseline associative learning capacities, resting metabolic rates and locomotor performance of both animal groups. After treatment, we tested the same functions as well as long-term memory.
Our results showed that CR animals had lower learning performance following caloric restriction. The effects of caloric restriction on memory recall varied and depended on the metabolism of the individual animal. Body mass loss was linked to memory test performance in the CR group, and lower performance was observed in individuals losing the most weight. While CR was observed to negatively impact learning, locomotor capacities were preserved in CR animals, and there were higher resting metabolic rates in the CR group. Our data reinforce the strong link between energy allocation and brain function, and suggest that in the context of food shortage, learning capacities could be a limiting parameter in the adaptation to a changing environment.
Highlights ► We focus on several biological systems which are impaired with age in grey mouse lemurs, as in humans. ►Similarities between human and mouse lemur are demonstrated in both normal and ...pathological ageing process. ►This smaller, rapidly developed and shorter-lived non-human primate could be a suitable model for human ageing research. ►This non-human primate model offer predictive biomarkers of longevity and neuropathological ageing.
Abstract We have previously shown that glucose utilization and glucose transport were impaired in the brain of rats made deficient in n-3 polyunsaturated fatty acids (PUFA). The present study ...examines whether n-3 PUFA affect the expression of glucose transporter GLUT1 and glucose transport activity in the endothelial cells of the blood–brain barrier. GLUT1 expression in the cerebral cortex microvessels of rats fed different amounts of n-3 PUFA (low vs. adequate vs. high) was studied. In parallel, the glucose uptake was measured in primary cultures of rat brain endothelial cells (RBEC) exposed to supplemental long chain n-3 PUFA, docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, or to arachidonic acid (AA). Western immunoblotting analysis showed that endothelial GLUT1 significantly decreased (−23%) in the n-3 PUFA-deficient microvessels compared to control ones, whereas it increased (+35%) in the microvessels of rats fed the high n-3 PUFA diet. In addition, binding of cytochalasin B indicated that the maximum binding to GLUT1 (Bmax) was reduced in deficient rats. Incubation of RBEC with 15 μM DHA induced the membrane DHA to increase at a level approaching that of cerebral microvessels isolated from rats fed the high n-3 diet. Supplementation of RBEC with DHA or EPA increased the 3 H-3- O -methylglucose uptake (reflecting the basal glucose transport) by 35% and 50%, respectively, while AA had no effect. In conclusion, we suggest that n-3 PUFA can modulate the brain glucose transport in endothelial cells of the blood–brain barrier, possibly via changes in GLUT1 protein expression and activity.
Converging evidence shows that the non-human primate gray mouse lemur (Microcebus murinus) is ideal for the study of the aging process and for testing the effects of new therapies and dietary ...interventions on age-associated pathologies. One such dietary supplement is resveratrol (RSV), a dietary polyphenolic compound with several positive effects on metabolic functions and longevity. However, little is known about the effect of RSV on the lemur sleep-wake cycle, which reflects mammalian brain function and health. In the present study, the authors investigated this effect by comparing sleep-wake cycles in adult lemurs based on electroencephalographic (EEG) rhythms. The effect of short-term RSV supplementation on the sleep-wake cycle of mouse lemurs was evaluated in entrained conditions (long-day photoperiods, light:dark 14:10). After 3 wks of RSV supplementation, the animals exhibited a significantly increased proportion of active-wake time, occurring mainly during the resting phase of the sleep-wake cycle (+163%). The increase in active-wake time with RSV supplementation was accompanied by a significant reduction of both paradoxical sleep (−95%) and slow-wave sleep (−38%). These changes mainly occurred during the resting phase of the sleep-wake cycle (RSV supplementation induced negligible changes in active-wake time during the active phase of the sleep-wake cycle). The present data suggest that RSV may be a potent regulator of sleep-wake rhythms and could be of major interest in the study of sleep perturbations associated with aging and neuropathology. (Author correspondence: aujard@mnhn.fr)
Abstract Cerebral metabolic rate of glucose (CMRg) is lower in individuals affected by cognitive decline and dementia, especially in Alzheimer's disease. However, as yet there is no consensus as to ...whether CMRg decreases during healthy aging. Epidemiological studies show that weekly consumption of fish abundant in ω3 fatty acids has a protective effect on cognition during aging. Thus, the primary objective of this human study was to use positron emission tomography analysis with18 F-fluorodeoxyglucose to evaluate whether supplementation with a fish oil rich in ω3 fatty acids increases cerebral glucose metabolism in young or elderly adults. Healthy young (23±5 y old; n =5) and elderly (76±3 y old; n =6) women and men were included in the study. Semi-quantitative expression of the data as ‘standardized uptake values’ showed that elderly participants had significantly lower cerebral glucose metabolism compared with the young group. However, when expressed quantitatively a CMRg, there was no effect of age or ω3 supplementation on glucose metabolism in any of the brains regions studied. Higher plasma triglyceride levels and higher plasma insulin levels were associated with lower CMRg in several regions, suggesting that a trend towards the metabolic syndrome may be associated with cerebral hypometabolism. We conclude that under these experimental conditions, ω3 supplementation did not affect brain glucose metabolism in the healthy elderly. Future studies in this area should address whether glucose intolerance or other conditions linked to the metabolic syndrome impact negatively on brain glucose metabolism and cognition.
Abstract The elderly reportedly have a significantly higher % of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma and red cell lipids. However, these observations are from a few small ...studies and the health status of the elderly in these studies is for the most part unclear. Since the elderly are susceptible to cardiovascular and neurological illnesses that seem to be related in part to lower intake of n-3 fatty acids it seems paradoxical that their blood levels of EPA and DHA would be higher than in young adults. We report here plasma fatty acid profiles and their response to supplementation with two types of fish oils from several of our recent studies in the moderately healthy elderly. We define the moderately healthy elderly as those who were in good physical condition, had no cognitive decline and, if present, in whom hypothyroidism, hyperlipidemia and/or hypertension were well-controlled. As shown previously, we confirm the higher % EPA and % total n-3 fatty acids (but not DHA) in fasting plasma and extend these findings to include higher plasma concentrations (mg/L) of n-3 fatty acids as well. The EPA-predominant supplement raised DHA only in the young, whereas the DHA-predominant supplement raised EPA more in the young than in the elderly. The moderately healthy elderly clearly have higher plasma n-3 fatty acids but whether this reflects differences in intake versus aging-related changes in n-3 fatty acid metabolism remains to be elucidated.
Expérimental/mécanismes cellulaires et moléculaires.
Le bouleversement des pratiques nutritionnelles et des habitudes de vie qui a eu lieu au cours du siècle dernier conduit aujourd’hui à une ...augmentation dramatique des pathologies chroniques sur l’ensemble du globe. En effet, bien que la longévité n’ait cessé d’augmenter dans cette période, cette augmentation s’accompagne depuis plusieurs décennies d’une augmentation massive de pathologies chroniques liées à l’âge. De ce fait, le bénéfice du gain de longévité est gâché par l’épidémie de syndrome métabolique et de démences séniles. Nous postulons ici que la très grande majorité de ces pathologies pourrait être évitée car elles ne sont pas liées à l’âge mais à l’inadéquation entre des apports caloriques élevés et une activité physique très faible. En effet, l’apparition et l’évolution de l’Homme ont eu lieu dans un environnement dans lequel la nourriture n’était pas nécessairement abondante. Récolter et chasser sa nourriture impliquait une activité physique importante, activité à laquelle la physiologie et la morphologie de notre espèce est adaptée. Depuis la révolution industrielle, la quantité d’activité physique n’a cessé de diminuer, alors que la quantité de calories ingérées n’a cessé de croître. C’est pourquoi nous avons proposé de tester les effets d’une intervention multi-modale combinant les effets d’une restriction calorique chronique modérée et d’activité physique chronique modérée, sur la santé et la longévité.
Cette étude est réalisée chez le microcèbe (Microcebus murinus), un primate d’une longévité moyenne de 6 ans. Les animaux sont suivis depuis leur inclusion dans l’étude, vers l’âge de 3 ans, jusqu’à leur mort naturelle. Les traitements suivants ont été appliqués : restriction calorique modérée (CR) et/ou activité physique (ACT). Ces traitements sont testés séparément (2 groupes différents : CR ou ACT) et en interaction ACT+CR). Cela nous permettra comprendre les effets synergiques potentiels des deux traitements. Chaque groupe est comparé à un groupe contrôle (CTL) maintenu en condition d’élevage standard. Ce groupe reçoit un régime composé de 15g de bouillie et 6g de fruits frais par jour (soit 105kJ.j−1 en moyenne). Le groupe CR reçoit 15 % de calories en moins que le groupe CTL (soit 89kJ.j−1 en moyenne). Le groupe ACT effectue 2×30minutes d’activité physique modérée par jour sur un tapis roulant (marche à une vitesse de 0,2m s−1 et 0° d’inclinaison (soit 720m.j−1).
Les premières données montrent une diminution significative du poids des animaux CR, ACT et CR+ACT. Des améliorations des performances cognitives chez les animaux du groupe CR+ACT ont également été observées.
Une diminution des pathologies liées à l’âge est attendue avec les traitements par rapport aux contrôles, ce qui devrait s’accompagner d’une durée de vie prolongée, les effets les plus forts étant attendus dans le groupe recevant les deux interventions (CR+ACT). Les premiers résultats de longévité seront disponibles après 2,5 ans d’étude, la durée nécessaire pour atteindre la durée de vie médiane des animaux CTL (5,7 ans). Cinq ans après le début de l’étude, 70 % des animaux CTL devraient être morts. De tels résultats contribueront à mieux comprendre et définir des niveaux optimaux d’apports caloriques et d’activité.
PDF
