Par Fathia DJELTI, postdoctorante de l’équipe BIOADAPT, UMR 7179 MECADEV - Mécanismes adaptatifs et Evolution

Aims: Age-related cognitive decline is well described, however the underlying mechanisms remain poorly understood and available pre-clinical models provide low predictive capacity for the clinic. Due to their similarity in brain structure with humans, non-human primates are considered a valid model to investigate cognitive deficits. The grey mouse lemur, Microcebus murinus, shows age-related changes similar to those observed in aging humans. Some older mouse lemurs show also evidence of Alzheimer’s pathology, such as amyloid plaques.The aim of the present study is 1) to identify animals with age-related cognitive deficit, and 2) to search for blood biomarkers (plasma A40 peptides and insulin sensitivity) that correlate with cognitive dysfunction.

Methods: The spatial memory was evaluated in middle-aged mouse lemurs (n=24) using the Barnes maze task and blood biomarkers were analysed in all animals.

Results: the spatial reference tasks revealed a large inter-individual variability in the middle-aged animals. Indeed, some of the animals performed as well as younger ones whereas a subgroup of old animals made more errors in the Barnes maze. Moreover, no significant correlation could be found between cognitive deficit and amyloid peptides (A40). Interestingly, the cognitive function was positively correlated with fasting plasma glucose levels.

Conclusion: the spatial memory task results distinguish two different populations in the mouse lemur: good and bad performers. The analyses of a series of blood biomarkers showed interesting perspectives that may ultimately lead to markers that can be associated with cognitive dysfunction in this non-human primate species. The cognitive defect is associated with an increase of fasting plasma glucose in middle-aged animals.