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.
Highlights
Common laboratory model organisms—yeast, nematodes (Caenorhabditis elegans), fruit flies (Drosophila melanogaster), and mice—have helped scientists substantially advance our understanding of neuropsychiatric diseases (Götz and Ittner, 2008; Nestler and Hyman, 2010)
In this task, old animals started exploring earlier than middle-aged and young animals, confirming a decrease in novelty-related anxiety in old animals compared to young animals
A study focusing on age differences in mental disorders in ten different European countries (McDowell et al, 2014) reported a lower prevalence of mood and anxiety disorders in older adults than in young adults in western European countries. Such observations suggest that the mouse lemur is a promising model for studying anxiety disorders across the lifespan
Summary
Common laboratory model organisms—yeast, nematodes (Caenorhabditis elegans), fruit flies (Drosophila melanogaster), and mice—have helped scientists substantially advance our understanding of neuropsychiatric diseases (Götz and Ittner, 2008; Nestler and Hyman, 2010). In a study by Languille and colleagues (Languille et al, 2015), the latency to the first movement in the open field, a parameter recognized as a marker of anxiety (Dal-Pan et al, 2011; Royo et al, 2018), differed significantly with age In this task (the open field test adapted for mouse lemurs, consisting of an empty squared box of 1 × 1 m), old animals started exploring earlier than middle-aged and young animals, confirming a decrease in novelty-related anxiety in old animals compared to young animals. In a more recent study (Zablocki-Thomas et al, 2018) assessing the relationship between early life inputs such as low birth weight and personality traits at older ages, Zablocki‐Thomas and colleagues confirmed the difference in anxiety behavior between young and aged mouse lemurs They performed emergence tests during which they measured the latency for the animals to escape from a small wooden box and return to their home cage. Such observations suggest that the mouse lemur is a promising model for studying anxiety disorders across the lifespan
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