Abstract
Mouse lemurs are non-human primate models of cerebral aging and neurodegeneration. Much smaller than other primates, they recapitulate numerous features of human brain aging, including progressive cerebral atrophy and correlation between regional atrophy and cognitive impairments. Characterization of brain atrophy in mouse lemurs has been done by MRI measures of regional CSF volume and by MRI measures of regional atrophy. Here, we further characterize mouse lemur brain aging using ex vivo MR microscopy (31 µm in-plane resolution). First, we performed a non-biased, direct volumetric quantification of dentate gyrus and extended Ammon's horn. We show that both dentate gyrus and Ammon's horn undergo an age-related reorganization leading to a growth of the dentate gyrus and an atrophy of the Ammon's horn, even in the absence of global hippocampal atrophy. Second, on these first MR microscopic images of the mouse lemur brain, we depicted cortical and hippocampal hypointense spots. We demonstrated that their incidence increases with aging and that they correspond either to amyloid deposits or to cerebral microhemorrhages.
Highlights
Post mortem studies of brain weight or brain volume and in vivo magnetic resonance imaging (MRI) studies have shown that a progressive cerebral atrophy starts during the adolescence, and accelerates after the 5th–6th decade [1,2,3]
Cerebral atrophy can be more pronounced and display a regional specificity: for example, Alzheimer’s disease (AD) is associated with a fast process of atrophy predominating in the medial temporal lobe, and in the hippocampal formation in particular [6,7]
In addition to the study of hippocampal atrophy, our high-resolution images allowed to detect hypointense spots in the cortex and hippocampal formation of lemurs. We demonstrated that their incidence increases with aging, and that they correspond either to amyloid deposits or to cerebral microhemorrhages that can both be detected by MRI
Summary
Post mortem studies of brain weight or brain volume and in vivo magnetic resonance imaging (MRI) studies have shown that a progressive cerebral atrophy starts during the adolescence, and accelerates after the 5th–6th decade [1,2,3]. A clear relationship has been established between age-related atrophy of specific brain regions and age-related decline in performance for the corresponding cognitive tasks: for example, hippocampal atrophy correlates with decline in memory performance [4,5]. A progressive cerebral atrophy appears in about 60% of aged animals [14,15,16,17], affecting several regions such as the caudate and splenium [18]. In lemurs, as in humans [4,19], there is a good correlation between age-related atrophy of the hippocampus and decline in spatial memory performance [18] To our knowledge, such a correlation between regional age-related atrophy and decline in the corresponding cognitive task has never been reported in other non-human primates [20,21,22]. Mouse lemurs appear as an efficient and valuable model of brain aging
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