Strengths and weaknesses of grey mouse lemur (Microcebus murinus) to model Alzheimer’s disease and neuropsychiatric conditions
- 1UMR7179 Mécanismes Adaptatifs et Evolution (MECADEV), France
- 2INSERM U1266 Institut de Psychiatrie et Neurosciences de Paris, France
To face the burden 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 are of primary interest. Of the non-human primates, to date, the gray mouse lemur (Microcebus murinus) has shown promising evidence of its translatability to humans. The present review reports the known advantages and limitations of using this species at all levels of investigation in the context of neuropsychiatric conditions.
In this easily bred Malagasy primate with a relatively short life span (approximately 12 years), age-related cognitive decline, amyloid angiopathy and risk factors (i.e., glucoregulatory imbalance) are congruent with those observed in humans. More specifically, analogous behavioral and psychological symptoms and neuropsychiatric symptoms of dementia (BPSD/NPS) to those in humans can be found in the aging mouse lemur. Aged mouse lemurs show typical age-related alterations of locomotor activity daily rhythms such as decreased rhythm amplitude, increased fragmentation, and increased activity during the resting-sleeping phase of the day and desynchronization with the light-dark cycle.
In addition, sleep deprivation successfully induces cognitive deficits in adult mouse lemurs, and the effectiveness of approved cognitive enhancers such as acetylcholinesterase inhibitors or N-methyl-D-aspartate antagonists is demonstrated in sleep-deprived animals. This result supports the translational potential of this animal model, especially for unravelling the mechanisms underlying dementia and for developing novel therapeutics to prevent age-associated cognitive decline.
In conclusion, actual knowledge of BPSD/NPS-like symptoms of age-related cognitive deficits in the gray mouse lemur and the recent demonstration of the similarity of these symptoms with those seen in humans offer promising new ways of investigating both the prevention and treatment of pathological aging.
Keywords: Microcebus, Aging, Primate model, Cognition, Alzheimer's disease, circadian rhythms
Received: 24 Jun 2019;
Accepted: 09 Oct 2019.
Copyright: © 2019 Pifferi, Epelbaum and Aujard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Fabienne Aujard, UMR7179 Mécanismes Adaptatifs et Evolution (MECADEV), Brunoy, 91800, Île-de-France, France, email@example.com