Light pollution and habitat fragmentation in the grey mouse lemur.

Light pollution, by changing organisms' behavior, affects locomotion, migration and can ultimately fragment the habitat. To investigate the effects of light pollution on habitat fragmentation, we conducted an experimental study on a nocturnal and photosensitive primate, the grey mouse lemur (Microcebus murinus). Twelve males were housed individually in an apparatus with two cages connected by two corridors, opaque and transparent. During 4 nights, the transparent corridor was illuminated by specific light intensities: 0 lx, 0.3 lx, 20 lx and 51.5 lx corresponding respectively to total darkness, full moon, minimal intensity recommended by the European standard EN-13201 on public lighting, and to light pollution recorded in an urban area. Each night, general activity, use of corridors and cage occupancy were recorded using an infrared camera. For the first time in a nocturnal primate, results demonstrate that light pollution changes the preference of use of corridors, modifies the locomotor pattern and limits the ability of animals to efficiently exploit their environment according to a light intensity-dependent relationship. However, results indicate that a dark corridor allows partial compensation partly preserving general activities. This study highlights the necessity to consider light pollution during the implementation of conservation plans and the relevance of nocturnal frames.

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

The biological clock generates circadian rhythms, with an endogenous period tau 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. In this study, we aimed to evaluate the link between the endogenous period and biomarkers of aging in order to investigate the mechanisms of the circadian resonance theory. We studied 39 middle-aged and aged Microcebus murinus, a nocturnal non-human primate whose endogenous period is about 23.1 h, measuring the endogenous period of locomotor activity, as well as several physiological and behavioral parameters (rhythm fragmentation and amplitude, energetic expenditure, oxidative stress, insulin-like growth factor-1 (IGF-1) concentrations and cognitive performances) in both males and females. We found that aged males with tau far from 24 h displayed increased oxidative stress. We also demonstrated a positive correlation between tau and IGF-1 concentrations, as well as learning performances, in males and females. Together these results suggest that a great deviation of tau from 24 h leads to increased biomarkers of age-related impairments.

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 ß3 adrenergic receptor (ß3AR) 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. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a ß3AR agonist could exert benefits in AD as well. METHODS: CL-316,243, a specific ß3AR agonist, was administered to the triple transgenic mouse model of AD (3xTg-AD) and non-transgenic controls from 15 to 16 months of age at a dose of 1 mg/kg/day i.p. RESULTS: Here, we show that ß3AR agonist administration decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a ß3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old). Locomotion, anxiety, and tau pathology were not modified. Finally, insoluble Aß42/Aß40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice. CONCLUSIONS: Overall, our results indicate that ß3AR stimulation reverses memory deficits and shifts downward the insoluble Aß42/Aß40 ratio in 16-month-old 3xTg-AD mice. As ß3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.

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. We found different effects according to sex and season. No impact of tau on mortality was found in females. However, in males, the deviation of tau from 24 h substantially correlates with an increase in mortality, particularly during the inactive season (winter). These results, comparable to other observations in mice or drosophila, show that captive gray mouse lemurs enjoy better fitness when their circadian period closely matches the environmental periodicity. In addition to their deep implications in health and aging research, these results raise further ecological and evolutionary issues regarding the relationships between fitness and circadian clock.

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. For the first time, we aimed to evaluate these physiological and cognitive costs that would partially explain the mechanisms of the circadian resonance hypothesis. We evaluated the potential costs of imposing a 26 h photoperiodic regimen compared to the classical 24 h entrainment measuring several physiological and cognitive parameters (body temperature, energetic expenditure, oxidative stress, cognitive performances) in males of a non-human primate (Microcebus murinus), a nocturnal species whose endogenous period is about 23.5 h. We found significant higher resting body temperature and energy expenditure and lower cognitive performances when the photoperiodic cycle length was 26 h. Together these results suggest that a great deviation of external cycles from tau leads to daily greater energetic expenditure, and lower cognitive capacities. To our knowledge, this study is the first to highlight potential mechanisms of circadian resonance theory.

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 (Microcebus murinus), 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). The alterations of the circadian timing system in M. murinus during aging show many similarities with those in human aging. Comparisons are drawn with other mammalian species (more specifically, with rodents, other non-human primates and humans) to demonstrate that the gray mouse lemur is a good complementary and alternative model for studying the circadian clock and, more broadly, brain aging and pathologies.