P1-006: Donepezil prevented the cognitive impairment induced by sleep deprivation in a nonhuman primate, the grey mouse lemur

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disease characterized by a gradual decline of cognitive functions. The successful outcome of therapeutic trials in transgenic AD mouse models provided unsatisfactory result in clinical set-up. At present, very few drugs are available for the symptomatic treatment of AD. Among them donepezil (dnpz) is the most prescribed drug as predicted by its ability to improve cognitive performance in several preclinical pharmacological models as well as in clinical studies. The grey mouse lemur, a non-human primate, is one of the very few animals that develop most of the AD-related neuropathologies spontaneously. Here we tested the efficacy of dnpz on impaired spatial memory performance following sleep deprivation (SD). The aim of our study was to test the efficacy of dnpz on cognitive performance in a primate and to validate this model for future drug testing programs of AD. Twenty seven adult male mouse lemurs aged between 2 to 3 years were used. Cognitive impairment was induced by 8h of SD and spatial memory performance was assessed in a radial arm maze. In a 2-day protocol, mouse lemurs underwent training and testing session on day 1. On day 2, animals were submitted to 8h SD and retested afterwards. Control (“Ctl”) animals went through the protocol without SD. The sleep deprived (“SDepd”) group was submitted to the above protocol but without dnpz and the treated (“SDepd + dnpz”) group received intraperitoneal dnpz (0.1mg/ kg) 3h before the cognitive function test during the SD procedure. Compared to “Ctl” group, the “SDepd” group, showed an increase of the number of errors (NE) and of the latency to reach the goal box during testing, which were significantly higher than that of training phase (NE=3.45± 0.93 vs 6.14±1.72, p=0.045; latency 293.2±43.8 vs 465.5±49.1, p=0.042). This SD-induced deficit was not observed in the “SDepd + dnpz” group. The present results indicate that donepezil was able to prevent the cognitive impairment induced by SD in the mouse lemur. This research was part of the PharmaCog consortium.