eLemur: A cellular-resolution 3D atlas of the mouse lemur brain.

The gray mouse lemur (), one of the smallest living primates, emerges as a promising model organism for neuroscience research. This is due to its genetic similarity to humans, its evolutionary position between rodents and humans, and its primate-like features encapsulated within a rodent-sized brain. Despite its potential, the absence of a comprehensive reference brain atlas impedes the progress of research endeavors in this species, particularly at the microscopic level.

Cognitive performance of grey mouse lemurs (Microcebus murinus) during a discrimination learning task: Effect of the emotional valence of stimuli.

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.

A vegetable fat-based diet delays psychomotor and cognitive development compared with maternal dairy fat intake in infant gray mouse lemurs.

Dairy fat has a unique lipid profile; it is rich in short- and medium-chain saturated fatty acids that induce ketone production and has a balanced ω6/ω3 ratio that promotes cognitive development in early life. Moreover, the high consumption of vegetable oils in pregnant and lactating women raises concerns regarding the quality of lipids provided to offspring. Here, we investigate maternal dairy fat intake during gestation and lactation in a highly valuable primate model for infant nutritional studies, the gray mouse lemur (Microcebus murinus).

Characterization of sinoatrial automaticity in Microcebus murinus to study the effect of aging on cardiac activity and the correlation with longevity.

Microcebus murinus, or gray mouse lemur (GML), is one of the smallest primates known, with a size in between mice and rats. The small size, genetic proximity to humans and prolonged senescence, make this lemur an emerging model for neurodegenerative diseases. For the same reasons, it could help understand how aging affects cardiac activity.

Increased oligodendrogenesis and myelination in the subventricular zone of aged mice and gray mouse lemurs.

The adult rodent subventricular zone (SVZ) generates neural stem cells (NSCs) throughout life that migrate to the olfactory bulbs (OBs) and differentiate into olfactory interneurons. Few SVZ NSCs generate oligodendrocyte precursor cells (OPCs). We investigated how neurogliogenesis is regulated during aging in mice and in a non-human primate (NHP) model, the gray mouse lemur.

Relationships between endogenous circadian period, physiological and cognitive parameters and sex in aged gray mouse lemurs ().

The biological clock generates circadian rhythms, with an endogenous period close to 24 h. The circadian resonance theory proposes that lifespan is reduced when endogenous period goes far from 24 h. It has been suggested that daily resetting of the circadian clock to the 24 h external photoperiod might induce marginal costs that would accumulate over time and forward accelerate aging and affect fitness.

Overview of age-related changes in psychomotor and cognitive functions in a prosimian primate, the gray mouse lemur (Microcebus murinus): Recent advances in risk factors and antiaging interventions.

Aging is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. Impaired glucose homeostasis is a major risk factor for cognitive decline in middle-aged humans, pointing at the existence of early markers of unhealthy aging. The gray mouse lemur (Microcebus murinus), a small lemuriform Malagasy primate, shows relatively slow aging with decreased psychomotor capacities at middle-age (around 5-year old).

Oscillatory Activity in Mouse Lemur Primary Motor Cortex During Natural Locomotor Behavior.

In arboreal environments, substrate orientation determines the biomechanical strategy for postural maintenance and locomotion. In this study, we investigated possible neuronal correlates of these mechanisms in an ancestral primate model, the gray mouse lemur. We conducted telemetric recordings of electrocorticographic activity in left primary motor cortex of two mouse lemurs moving on a branch-like small-diameter pole, fixed horizontally, or vertically.

Repurposing beta-3 adrenergic receptor agonists for Alzheimer's disease: beneficial effects in a mouse model.

Background: Old age, the most important risk factor for Alzheimer's disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3 adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits, and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation.

Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease.

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF.

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).

Survival is reduced when endogenous period deviates from 24 h in a non-human primate, supporting the circadian resonance theory.

Circadian rhythms are ubiquitous attributes across living organisms and allow the coordination of internal biological functions with optimal phases of the environment, suggesting a significant adaptive advantage. The endogenous period called tau lies close to 24 h and is thought to be implicated in individuals' fitness: according to the circadian resonance theory, fitness is reduced when tau gets far from 24 h. In this study, we measured the endogenous period of 142 mouse lemurs (Microcebus murinus), and analyzed how it is related to their survival.

EthoLoop: automated closed-loop neuroethology in naturalistic environments.

Accurate tracking and analysis of animal behavior is crucial for modern systems neuroscience. However, following freely moving animals in naturalistic, three-dimensional (3D) or nocturnal environments remains a major challenge. Here, we present EthoLoop, a framework for studying the neuroethology of freely roaming animals.

Physiological and cognitive consequences of a daily 26 h photoperiod in a primate exploring the underlying mechanisms of the circadian resonance theory.

The biological clock expresses circadian rhythms, whose endogenous period (tau) is close to 24 h. Daily resetting of the circadian clock to the 24 h natural photoperiod might induce marginal costs that would accumulate over time and forward affect fitness. It was proposed as the circadian resonance theory.

Evidence of the Role of Omega-3 Polyunsaturated Fatty Acids in Brain Glucose Metabolism.

In mammals, brain function, particularly neuronal activity, has high energy needs. When glucose is supplemented by alternative oxidative substrates under different physiological conditions, these fuels do not fully replace the functions fulfilled by glucose. Thus, it is of major importance that the brain is almost continuously supplied with glucose from the circulation.

Profiling torpor-responsive microRNAs in muscles of the hibernating primate Microcebus murinus.

When food scarcity is coupled with decreased temperatures, gray mouse lemurs (Microcebus murinus) depress their metabolic rates and retreat into bouts of either daily torpor or multi-day hibernation, without dramatically dropping body temperatures like other 'traditional hibernators'. Rapid and reversible mechanisms are required to coordinate the simultaneous suppression of energetically expensive processes and activation of pro-survival pathways critical for successful torpor-arousal cycling. MicroRNAs, a class of endogenous non-coding small RNAs, are effective post-transcriptional regulators that modulate all aspects of cellular function.

The age-performance relationship in the general population and strategies to delay age related decline in performance.

The age-performance relationship describes changes in the organism's structural and functional capabilities over the course of the lifespan. The typical, empirical pattern is an asymmetrical inverted-U shape association with peak capacity occurring early in life. This process is well described in the literature, with an increasing interest in features that characterize this pattern, such as the rate of growth, age of peak performance, and rate of decline with aging.

Strengths and Weaknesses of the Gray Mouse Lemur () as a Model for the Behavioral and Psychological Symptoms and Neuropsychiatric Symptoms of Dementia.

To face the load of the prevalence of Alzheimer's disease in the aging population, there is an urgent need to develop more translatable animal models with similarities to humans in both the symptomatology and physiopathology of dementia. Due to their close evolutionary similarity to humans, non-human primates (NHPs) are of primary interest. Of the NHPs, to date, the gray mouse lemur () has shown promising evidence of its translatability to humans.

Daily Torpor and Sleep in a Non-human Primate, the Gray Mouse Lemur ().

Daily torpor is an energy-saving process that evolved as an extension of non-rapid eye movement (NREM) sleep mechanisms. In many heterothermic species there is a relation between torpor expression and the repartition of the different behavioral states of sleep. Despite the presence of sleep during this period of hypothermia, torpor induces an accumulation of sleep debt which results in a rebound of sleep in mammals.

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.

The Biological Clock in Gray Mouse Lemur: Adaptive, Evolutionary and Aging Considerations in an Emerging Non-human Primate Model.

Circadian rhythms, which measure time on a scale of 24 h, are genetically generated by the circadian clock, which plays a crucial role in the regulation of almost every physiological and metabolic process in most organisms. This review gathers all the available information about the circadian clock in a small Malagasy primate, the gray mouse lemur (), and reports 30 years data from the historical colony at Brunoy (France). Although the mouse lemur has long been seen as a "primitive" species, its clock displays high phenotypic plasticity, allowing perfect adaptation of its biological rhythms to environmental challenges (seasonality, food availability).

Caloric restriction, longevity and aging: Recent contributions from human and non-human primate studies.

The health benefits of chronic caloric restriction (CR) resulting in lifespan extension are well established in many species and has been recently demonstrated also in non-human primates, but its effects in humans remain to be proven on a long-term basis. CR might be a very efficient anti-aging strategy but its definition and limits must be well understood before envisaging to apply it to human. In this review, we first report and compare the recently issued CR studies in non-human primates and humans and then try to understand what an optimal caloric intake is.

Publisher Correction: Lipidome determinants of maximal lifespan in mammals.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

The sensory thalamus and visual midbrain in mouse lemurs.

Mouse lemurs are the smallest of extant primates and are thought to resemble early primates in many ways. We provide histological descriptions of the major sensory nuclei of the dorsal thalamus and the superior colliculus (SC) of mouse lemurs (Microcebus murinus). The dorsal lateral geniculate nucleus has the six layers typical of strepsirrhine primates, with matching pairs of magnocellular, parvocellular, and koniocellular layers, one of each pair for each eye.

Promoting healthspan and lifespan with caloric restriction in primates.

Recent data confirmed the efficiency of caloric restriction for promoting both healthspan and lifespan in primates, but also revealed potential adverse effects at the central level. This paper proposes perspectives and future directions to counterbalance potential adverse effects. Efforts should be made in combining nutrition-based clinical protocols with therapeutic and/or behavioral interventions to aim for synergetic effects, and therefore delay the onset of age-related diseases without adverse effects.