Abstract
Cerebral atrophy is one of the most widely brain alterations associated to aging. A clear relationship has been established between age-associated cognitive impairments and cerebral atrophy. The mouse lemur (Microcebus murinus) is a small primate used as a model of age-related neurodegenerative processes. It is the first non-human primate in which cerebral atrophy has been correlated with cognitive deficits. Previous studies of cerebral atrophy in this model were based on time consuming manual delineation or measurement of selected brain regions from magnetic resonance images (MRI). These measures could not be used to analyse regions that cannot be easily outlined such as the nucleus basalis of Meynert or the subiculum. In humans, morphometric assessment of structural changes with age is generally performed with automated procedures such as voxel-based morphometry (VBM). The objective of our work was to perform user-independent assessment of age-related morphological changes in the whole brain of large mouse lemur populations thanks to VBM. The study was based on the SPMMouse toolbox of SPM 8 and involved thirty mouse lemurs aged from 1.9 to 11.3 years. The automatic method revealed for the first time atrophy in regions where manual delineation is prohibitive (nucleus basalis of Meynert, subiculum, prepiriform cortex, Brodmann areas 13–16, hypothalamus, putamen, thalamus, corpus callosum). Some of these regions are described as particularly sensitive to age-associated alterations in humans. The method revealed also age-associated atrophy in cortical regions (cingulate, occipital, parietal), nucleus septalis, and the caudate. Manual measures performed in some of these regions were in good agreement with results from automatic measures. The templates generated in this study as well as the toolbox for SPM8 can be downloaded. These tools will be valuable for future evaluation of various treatments that are tested to modulate cerebral aging in lemurs.
Highlights
Cerebral alterations associated with aging affect quality of life for millions of people
Evaluation of cerebral atrophy with voxel-based morphometry (VBM) revealed a negative correlation between the total gray matter (GM) volume and age (r = −0.4, p = 0.02, Figure 3E)
Subcortical regions such as the caudate or putamen were affected by aging. Other clusters such as the nucleus basalis of Meynert, the nucleus septalis, the subiculum, the prepiriform cortex, or the hypothalamus were altered during aging
Summary
Cerebral alterations associated with aging affect quality of life for millions of people. This primate can be a useful compromise between practicality and relatedness to humans for laboratory studies (Languille et al, 2012) Previous studies in this model have shown atrophy of distinct brain regions (cortical regions, hippocampus, the caudate nucleus, and white matter regions such as the splenium) (Picq et al, 2012) including atrophy of some hippocampal subfields (Bertrand et al, 2013) as well as increased levels of cerebrospinal fluid (CSF) (Kraska et al, 2011). Previous studies of cerebral atrophy in mouse lemurs were based on the manual and tedious segmentation of selected regions of interest (ROI), or on the manual measurement of cortical thickness from T2-weighted magnetic resonance images (MRI)
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