Strengths and Weaknesses of the Gray Mouse Lemur (Microcebus murinus) as a Model for the Behavioral and Psychological Symptoms and Neuropsychiatric Symptoms of Dementia

Abstract

To face the load 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 (NHPs) are of primary interest. Of the NHPs, 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 unraveling 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.

Overview of age‐related changes in psychomotor and cognitive functions in a prosimian primate, the gray mouse lemur (Microcebus murinus): Recent advances in risk factors and antiaging interventions

“…The gray mouse lemur presents specific features that make it an appropriate model for nutrition studies. In addition to the fact that it is easy to raise and handle (Languille et al, 2012b) it has an omnivorous diet based on the consumption of fruits, flowers, gum, arthropods, and small vertebrates (Dammhahn & Kappeler, 2008) with a relatively long lifespan that allows long‐term, but still feasible nutritional interventions (Pifferi et al, 2019, 2018).…”

Mouse lemur transcriptomic atlas informs primate genes, mutations, physiology, and disease

“…The copyright holder for this preprint this version posted August 7, 2022. ; https://doi.org/10.1101/2022.08.06.503035 doi: bioRxiv preprint Tabula Microcebus manuscript 2, p. 13 brought together by V(D)J recombination during B lymphocyte development to create antibody diversity 27 . We first used BLAST to search the mouse lemur genome (Mmur 3.0) for homologs of human Ig constant region sequences that are missing in the current annotation (NCBI Microcebus Murinus Annotation Release 101), which identified the IGG constant region.…”

“…provide an appealing model for the study of primate biology and health [7][8][9] . Their physiology has been studied for decades in laboratory colonies, especially their circadian and dramatic seasonal rhythms, metabolism, cognition and ageing [10][11][12][13][14][15][16] .…”

Mouse lemur, a new animal model to investigate cardiac pacemaker activity in primates

“…1A). 34 Since the frequency of heart contractions in mammals is determined by their body size, in order to sustain physiological and metabolic needs, 35,36 we compared our results on mouse lemurs to previous findings on mammals of similar sizes, such as rats and mice. We also compared the cardiac activity in mouse lemurs and humans when possible and relevant.…”