Body mass loss correlates with cognitive performance in primates under acute caloric restriction conditions.

Brain functions are known to consume high levels of energy, thus, the integrity of cognitive performance can be drastically impacted by acute caloric restriction. In this study, we tested the impact of a 40% caloric restriction on the cognitive abilities of the grey mouse lemur (Microcebus murinus). Twenty-three male mouse lemurs were divided into two groups: 13 control animals (CTL) that were fed with 105kJ/day and 10calorie restricted (CR) animals that received 40% less food (63kJ/day) than the CTL animals. The animals were fed according to their group for 19days. Before treatment, we assessed baseline associative learning capacities, resting metabolic rates and locomotor performance of both animal groups. After treatment, we tested the same functions as well as long-term memory. Our results showed that CR animals had lower learning performance following caloric restriction. The effects of caloric restriction on memory recall varied and depended on the metabolism of the individual animal. Body mass loss was linked to memory test performance in the CR group, and lower performance was observed in individuals losing the most weight. While CR was observed to negatively impact learning, locomotor capacities were preserved in CR animals, and there were higher resting metabolic rates in the CR group. Our data reinforce the strong link between energy allocation and brain function, and suggest that in the context of food shortage, learning capacities could be a limiting parameter in the adaptation to a changing environment.

The grey mouse lemur: a non-human primate model for ageing studies.

The use of non-human primate models is required to understand the ageing process and evaluate new therapies against age-associated pathologies. The present article summarizes all the contributions of the grey mouse lemur Microcebus murinus, a small nocturnal prosimian primate, to the understanding of the mechanisms of ageing. Results from studies of both healthy and pathological ageing research on the grey mouse lemur demonstrated that this animal is a unique model to study age-dependent changes in endocrine systems, biological rhythms, thermoregulation, sensorial, cerebral and cognitive functions.

MRI description of cerebral atrophy in mouse lemur primates.

We assessed cerebral atrophy in mouse lemur primates (Microcebus murinus) by estimating CSF volume in their brains from 4.7 Tesla T2-weighted magnetic resonance images. Thirty animals aged from 1 to 10.3 years were imaged, 14 of them were followed for up to 2 years. Seven of these animals were examined for neuropathology. In 12 out of 17 animals older than 3.5 years, CSF volumes were increased. A subgroup of six animals had severe atrophy of the temporal lobe. Another subgroup of five animals displayed diffuse atrophy in addition to the temporal atrophy. One animal had a dilation of the external part of the temporal horn of the lateral ventricle in addition to the temporal atrophy. The three animals with diffuse atrophy that could be studied for neuropathology had diffuse cerebral amyloid deposits detected by immunocytochemistry. The other animals did not display amyloid deposits. Relations between the different types of atrophy as well as their causes will have to be assessed in future studies.

Cerebral T2-weighted signal decrease during aging in the mouse lemur primate reflects iron accumulation.

4.7 Tesla T2-weighted magnetic resonance images showed a highly significant signal decrease in the pallidum, substantia nigra, putamen, and a less significant decrease in the thalamus and the caudate of aging mouse lemurs (Microcebus murinus). We evaluated the contribution of iron deposits to the signal decrease comparing Perls' stained histological sections of six mouse lemurs brains aged 1 to 10 years to magnetic resonance images. In young animals, none of the brain structures was stained. A large number of iron deposits were visible in the pallidum and substantia nigra of aged animals and a moderate number in the middle aged ones. In the putamen, few iron deposits were visible in aged and middle-aged animals. The thalamus and the caudate appeared unstained with Perls' technique; iron was too low to be detected. The intensification of the reaction by diaminobenzidine revealed iron deposits in the thalamus of aging animals. This study suggests that in mouse lemurs, iron deposits are responsible for T2-weighted signal decrease in the central gray nuclei.

T2-weighted MRI studies of mouse lemurs: a primate model of brain aging.

Previous histological and behavioral studies of aging mouse lemurs have demonstrated changes similar to those observed in elderly humans and in patients with Alzheimer's disease. We explored 18 animals of ages 6 months to 9 years. Axial T2-weighted images of the brain were performed on a 4.7 Tesla Bruker Biospec 47/30 system. We estimated cerebral atrophy by adding measures of high signal areas characteristic of cerebrospinal fluid (interlobular and sylvian fissures, lateral and third ventricles) of four contiguous cortical slices. We observed a significant increase of cerebral atrophy with aging and one case of an apathetic 8-year-old animal presenting a considerably higher cerebral atrophy. We also observed high correlations between decreased signal intensities and age for the pallidum, the substantia nigra, and the putamen. These results suggest that aging mouse lemurs present similar magnetic resonance images of cerebral alterations to those encountered in aging humans and that high-field T2-weighted magnetic resonance images can help in the early detection, in vivo, of animals suspected of pathological aging.

Age dependence of the T2-weighted MRI signal in brain structures of a prosimian primate (Microcebus murinus).

Mouse lemurs (Microcebus murinus) are prosimian primates described to be convenient models of brain aging. We observed very high correlations between the T2-weighted magnetic resonance imaging (MRI) signal decrease and the natural logarithm of age in the basal ganglia. The correlation coefficient was higher for the pallidum (r = 0.95, P < 0.0001) than for other structures. We suggest that the ratio of the pallidum intensity divided by the amygdala and temporal lobe intensity should be a valuable non-invasive marker of age and of cerebral aging. It should be particularly useful for the non-invasive assessment of interventions and drugs that affect the aging process.

Effects of aging upon recent memory in Microcebus murinus.

Four young (2 to 4-year-old) and four aged (9 to 10-year-old) grey mouse lemurs (Microcebus murinus) were given a simple visual discrimination task, and a delayed response visual discrimination task with variable retention delay. The response to the test is a motor one, that consists of choosing one out of four corridors of an apparatus based upon the degree of illumination. The aged animals did not show any learning deficiency, and were capable of memorizing the task for several months. However, they were more sensitive to the length of the delay in the delayed response task than the young animals. It is, therefore, possible to argue that the memory for recent stimulus events is affected during aging. These results corroborate those obtained in other primates, and demonstrate the usefulness of the grey mouse lemur as a new animal model for analyzing aging.