Background: Mouse lemurs are small primates (12 cm, maximal life span of 12 years). While aging, they can display cerebral atrophy (1), behavioral alterations (2), amyloidosis, gliosis, and tau pathology (3). Here, we further evaluated these alterations and their relationship in large cohorts of animals. Methods: Cerebral atrophy was assessed from 3D-MR images (isotropic resolution = 234μm) in two cohorts of 30 and 34 animals (aged from 1.9 to 11.8 years). We either quantified regional amount of cerebro-spinal fluid (CSF) in areas surrounding the cortex (2) or measured the size of brain structures or cortical thickness. The behavior of 16 animals (2 to 8.4 year-old) was evaluated. Executive functions were assessed by discrimination and shift tasks, while spatial memory was tested in a Barnes maze. Histological evaluation of amyloid, astrogliosis, and Tau pathology was performed in 2 non atrophied animals and 3 atrophied lemurs. Results: Cerebral atrophy increased with age in mouse lemurs. Pericortical CSF accumulation started in regions surrounding the frontal cortex, then reached the temporal and/or parietal regions and finally occurred in occipital regions. Age-related atrophy of the caudate and splenium occurred in most aged animals. Shrinkage of the hippocampus, entorhinal cortex and septal region was showed in a subgroup of aged animals. Regarding the cortical thickness, temporal and cingulate areas were the most atrophied whereas frontal and parietal cortices were spared. Cognitive evaluations showed that both executive functions and spatial memory declined with aging. Impairment of executive functions was associated with atrophy of the septal region while spatial memory performance was related to atrophy of the hippocampus and entorhinal cortex. Extracellular amyloid deposits were detected in 2 of the 3 atrophied lemurs. More interestingly, the severity of the atrophy seemed correlated to the level of intracellular amyloid deposits and reactive astrogliosis accumulation in hippocampal regions. Conclusions: We characterized cerebral atrophy in aged mouse lemurs. This atrophy is correlated to behavioral alterations. It seems to be more associated to intracellular amyloid deposition than to extracellular amyloid deposits.
References:
1. Dhenain et al., MRM, 2003. 2. Picq. Exp Gerontol, 2007. 3. Mestre-Frances et al., Neurob Dis, 2000.
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