Stiftung Tierärztliche Hochschule Hannover (TiHo)

Sex-specific patterns of age-related cerebral atrophy in a nonhuman primate Microcebus murinus.

Steadily aging populations result in a growing need of research regarding age-related brain alterations and neurodegenerative pathologies. By allowing a good transfer of results to humans, nonhuman primates, such as the gray mouse lemur (Microcebus murinus), have gained increasing attention in this field. The aim of this study was to investigate a possible linkage of age and brain morphometry in a large number (n=59) of mouse lemurs from our breeding colony (Institute of Zoology, University of Veterinary Medicine Hannover, Germany) and to explore, whether patterns of brain-aging that have previously been described in a different subpopulation (Museum of Natural History, Brunoy, France) can be generalized across colonies. For the first time, we additionally examined how atrophy-induced brain alterations relate to sex in a nonhuman primate. Three-dimensional (FOV: 3x3x3 cm, matrix: 128x128x128), T2-weighted in vivo MRI was performed on a 7 T Bruker Pharmascan (70/16; Bruker BioSpin MRI GmbH) equipped with a high performance gradient system (300 mT/m max. amplitude; 0.35 ms rise time). In total, 59 animals (28♀♀/31♂♂) between 1.0 to 11.9 years were scanned under isoflurane anaesthesia. We calculated areas of different brain regions, measured cortical thicknesses, and evaluated the expansion of cerebrospinal fluid on a standardized set of reference slices. Correlation analyses between structural measurements and age in all subjects revealed significant brain atrophies with increasing age, especially for the volume of the caudate nucleus and the temporo-occipital region. Sex-specific analyses showed a strong decline in thickness of the occipital, parietal, and frontal cortex in males. Only old females presented high values of ventricular cerebrospinal fluid expansion. Our global findings (males and females combined) revealed age-related brain alterations of the caudate nucleus and temporal structures as well as cortical thickness decline of the cingulate and occipital lobe, which is consistent with results from the Brunoy mouse lemur colony. These changes, therefore, can be considered as universal patterns of age-related brain atrophy in mouse lemurs. In addition, our study provides first evidence for sex-specific, age-related brain alterations in a nonhuman primate, showing similarities to sex-specific cerebral atrophy in humans. Thus, future studies in mouse lemurs may help elucidating this aspect of human brain aging and its pathophysiology to develop novel treatment strategies.

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