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Pifferi, F.

Publications and source records attributed to Pifferi, F..

2 recordsLinked to original sources

Adult survival is reduced when endogenous period deviates from 24h in a non-human primate (Microcebus murinus), depending on sex and season

SummaryCircadian 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 24h and is thought to be implicated in individuals’ fitness: according to the circadian resonance theory, fitness is reduced when tau gets far to 24h. In this study, we measured the endogenous period of 142 mouse lemurs (Microcebus. murinus), and analyzed how it affects 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 24h substantially increased 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.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology

Repurposing beta3-adrenergic receptor agonists for Alzheimer's disease: Beneficial effects on recognition memory and amyloid pathology in a mouse model.

ABSTRACTOld 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. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well.Here, we show that β3AR agonist administration (CL-316,243, 1 mg/kg/day i.p., from 15 to 16 months of age) decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a β3AR 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 Aβ42/Aβ40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice.Overall, our results indicate that β3AR stimulation reverses memory deficits and shifts downward the insoluble Aβ42/Aβ40 ratio in 16-month-old 3xTg-AD mice. As β3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pharmacology and toxicology