Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates

The mouse lemur (Microcebus murinus) is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12) and aged (n = 8) adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination.     

Are There Age-Related Differences in the Ability to Learn Configural Responses?

Age is often associated with a decline in cognitive abilities that are important for maintaining functional independence, such as learning new skills. Many forms of motor learning appear to be relatively well preserved with age, while learning tasks that involve associative binding tend to be negatively affected. The current study aimed to determine whether age differences exist on a configural response learning task, which includes aspects of motor learning and associative binding. Young (M = 24 years) and older adults (M = 66.5 years) completed a modified version of a configural learning task. Given the requirement of associative binding in the configural relationships between responses, we predicted older adults would show significantly less learning than young adults. Older adults demonstrated lower performance (slower reaction time and lower accuracy). However, contrary to our prediction, older adults showed similar rates of learning as indexed by a configural learning score compared to young adults. These results suggest that the ability to acquire knowledge incidentally about configural response relationships is largely unaffected by cognitive aging. The configural response learning task provides insight into the task demands that constrain learning abilities in older adults.     

Behavioral compensations in a positional learning and memory task by aged monkeys

The present experiment assessed learning and memory of a positional task by evaluating behavioral strategies as well as accuracy of a task in four young and four aged monkeys. They were tested in a delayed response (DR) task that has been widely used to study animal models of aging. The task consisted of two phases; an acquisition of the task and a positional memory test with five delay times (1-30 s). There was no clear difference between age groups in the number of trials needed for acquisition of the task. However, an analysis of behavior revealed differences in behavioral characteristics displayed during testing. The young monkeys showed various irrelevant behaviors during the execution of the task. In contrast, the aged monkeys consistently concentrated on the task exhibiting no behaviors irrelevant to the task. These results showed than the aged monkeys' performance was supported by a different behavioral strategy from the young monkeys. The results of the memory test were similar to those of the acquisition on the accuracy and the behavior. The aged monkeys depended on behavioral cues to preserve their positional memory, especially during the task. The present study suggests that cognitive impairments in aged monkeys can be compensated for by employing behavioral strategies.     

Daily Rhythms of Core Temperature and Locomotor Activity Indicate Different Adaptive Strategies to Cold Exposure in Adult and Aged Mouse Lemurs Acclimated to a Summer-Like Photoperiod

Daily variations in core temperature (Tc) within the normothermic range imply thermoregulatory processes that are essential for optimal function and survival. Higher susceptibility towards cold exposure in older animals suggests that these processes are disturbed with age. In the mouse lemur, a long-day breeder, we tested whether aging affected circadian rhythmicity of Tc, locomotor activity (LA), and energy balance under long-day conditions when exposed to cold. Adult (N?=?7) and aged (N?=?5) mouse lemurs acclimated to LD14/10 were exposed to 10–day periods at 25 and 12°C. Tc and LA rhythms were recorded by telemetry, and caloric intake (CI), body mass changes, and plasma IGF-1 were measured. During exposure to 25°C, both adult and aged mouse lemurs exhibited strong daily variations in Tc. Aged animals exhibited lower levels of nocturnal LA and nocturnal and diurnal Tc levels in comparison to adults. Body mass and IGF-1 levels remained unchanged with aging. Under cold exposure, torpor bout occurrence was never observed whatever the age category. Adult and aged mouse lemurs maintained their Tc in the normothermic range and a positive energy balance. All animals exhibited increase in CI and decrease in IGF-1 in response to cold. The decrease in IGF-1 was delayed in aged mouse lemurs compared to adults. Moreover, both adult and aged animals responded to cold exposure by increasing their diurnal LA compared to those under Ta?=?25°C. However, aged animals exhibited a strong decrease in nocturnal LA and Tc, whereas cold effects were only slight in adults. The temporal organization and amplitude of the daily phase of low Tc were particularly well preserved under cold exposure in both age groups. Sexually active mouse lemurs exposed to cold thus seemed to prevent torpor exhibition and temporal disorganization of daily rhythms of Tc, even during aging. However, although energy balance was not impaired with age in mouse lemurs after cold exposure, aging was associated with lower LA and Tc during the night and delayed decrease in IGF-1. This might reflect that adaptive strategies to cold exposure differ with age in mouse lemurs acclimated to a summer-like photoperiod.     

Age-related effects on the biological clock and its behavioral output in a primate

In humans, activity rhythms become fragmented and attenuated in the elderly. This suggests an alteration of the circadian system per se that could in turn affect the expression of biological rhythms. In primates, very few studies have analyzed the effect of aging on the circadian system. The mouse lemur provides a unique model of aging in non-human primates. To assess the effect of aging on the circadian system of this primate, we recorded the circadian and daily rhythms of locomotor activity of mouse lemurs of various ages. We also examined age-related changes in the daily rhythm of immunoreactivities for vasoactive intestinal polypeptide (VIP) and arginine-vasopressin (AVP) in suprachiasmatic nucleus neurons (SCN), two major peptides of the biological clock. Compared to adult animals, aged mouse lemurs showed a significant increase in daytime activity and an advanced activity onset. Moreover, when maintained in constant dim red light, aged animals exhibited a shortening of the free-running period compared to adult animals. In adults, AVP immunoreactivity (ir) peaked during the second part of the day, and VIP ir peaked during the night. In aged mouse lemurs, the peaks of AVP ir and VIP ir were significantly shifted with no change in amplitude. AVP ir was most intense at the beginning of the night; whereas, VIP ir peaked at the beginning of the daytime. A weakened oscillator could account for the rhythmic disorders often observed in the elderly. Changes in the daily rhythms of AVP ir and VIP ir may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby modify the expression of some biological rhythms.     

Virtual navigation in humans: the impact of age, sex, and hormones on place learning

Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20-90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20-39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.     

Hippocampus, ageing, and taste memories

Previous studies have shown that ageing may induce deficits in hippocampal-dependent learning and memory tasks, the spatial task being most extensively applied in rats. It is proposed that taste learning and memory tasks may assist in understanding the ageing of memory systems, giving access to a more complete picture. Taste learning tasks allow us to explore a variety of learning phenomena in safe and aversive memories using similar behavioral procedures. In demanding the same sensory, response, and motivational requirements, this approach provides reliable comparisons between the performance of hippocampal lesioned and aged rats in different types of memory. Present knowledge on the effect of both ageing and hippocampal damage in complex taste learning phenomena is reviewed. Besides inducing deficits in hippocampal-dependent phenomena, such as blocking of conditioned taste aversion, while at the same time leaving intact nonhippocampal-dependent effects, such as latent inhibition, ageing is also associated with an increased neophobia by previous aversive taste memories and enhanced taste aversion conditioning which cannot be explained by age-related changes in taste or visceral distress sensitivity. In all, the results indicate a peculiar organization of the memory systems during aging that cannot be explained by a general cognitive decline or exclusively by the decay of the hippocampal function.     

Corticomuscular coherence with and without additional task in the elderly

Aging and dual-task paradigms often degrade fine motor performance, but the effects of aging on correlated neural activity between motor cortex and contracting muscle are unknown during dual tasks requiring fine motor performance. The purpose of this study was to compare corticomuscular coherence between young and elderly adults during the performance of a unilateral fine motor task and concurrent motor and cognitive tasks. Twenty-nine healthy young (18-38 yr) and elderly (61-75 yr) adults performed unilateral motor, bilateral motor, concurrent motor-cognitive, and cognitive tasks. Peak corticomuscular coherence between the electroencephalogram from the primary motor cortex and surface electromyogram from the first dorsal interosseous muscle was compared during steady abduction of the index finger with visual feedback. In the alpha-band (8-14 Hz), corticomuscular coherence was greater in elderly than young adults especially during the motor-cognitive task. The beta-band (15-32 Hz) corticomuscular coherence was higher in elderly than young adults across unilateral motor and dual tasks. In addition, beta-band corticomuscular coherence in the motor-cognitive task was negatively correlated with motor output error across young but not elderly adults. The results suggest that 1) corticomuscular coherence was increased in senior age with a greater influence of an additional cognitive task in the alpha-band and 2) individuals with greater beta-band corticomuscular coherence may exhibit more accurate motor output in young, but not elderly adults, during steady contraction with visual feedback.     

An Operant Intra-/Extra-dimensional Set-shift Task for Mice

Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric diseases. The most widely used neuropsychological tests for the evaluation of attentional set-shifting in human subjects are the Wisconsin Card Sorting Test (WCST) and the CANTAB Intra-/Extra-dimensional set shift task (ID/ED). These tasks have proven clinical relevance and have been modified and successfully adapted for research in animal models. However, currently available tasks for rodents present several limitations, mainly due to their manual-based testing procedures, which are hampering translational advances in psychiatric medicine. To overcome these limitations and to better mimic the original version in primates, we present the development of a novel operant-based two-chamber ID/ED "Operon" task for rodents. We demonstrated the effectiveness of this novel task to measure different facets of cognitive flexibility in mice including attentional set formation and shifting, and reversal learning. Moreover, we show the high flexibility of this task in which three different perceptual dimensions can be manipulated with a high number of stimuli cues for each dimension. This novel ID/ED Operon task can be an effective preclinical tool for drug testing and/or large genetic screening relevant to the study of executive dysfunction and cognitive symptoms found in psychiatric disorders.     

Sequence Skill Acquisition and Off-Line Learning in Normal Aging

It is well known that certain cognitive abilities decline with age. The ability to form certain new declarative memories, particularly memories for facts and events, has been widely shown to decline with advancing age. In contrast, the effects of aging on the ability to form new procedural memories such as skills are less well known, though it appears that older adults are able to acquire some new procedural skills over practice. The current study examines the effects of normal aging on procedural memory more closely by comparing the effects of aging on the encoding or acquisition stage of procedural learning versus its effects on the consolidation, or between-session stage of procedural learning. Twelve older and 14 young participants completed a sequence-learning task (the Serial Reaction Time Task) over a practice session and at a re-test session 24 hours later. Older participants actually demonstrated more sequence skill during acquisition than the young. However, older participants failed to show skill improvement at re-test as the young participants did. Age thus appears to have a differential effect upon procedural learning stages such that older adults'' skill acquisition remains relatively intact, in some cases even superior, compared to that of young adults, while their skill consolidation may be poorer than that of young adults. Although the effect of normal aging on procedural consolidation remains unclear, aging may actually enhance skill acquisition on some procedural tasks.     

Evidence that Ames dwarf mice age differently from their normal siblings in behavioral and learning and memory parameters

There is strong evidence supporting the deleterious effects of aging on learning and memory and behavioral parameters in normal mice. However, little is known about the Ames dwarf mouse, which has a Prop-1 gene mutation resulting in deficiencies in growth hormone, thyroid-stimulating hormone, and prolactin. These mice are much smaller and live significantly longer than their normal siblings. Using the elevated plus-maze, locomotor activity meters, and an inhibitory avoidance learning task, the present study compared Ames dwarf mice to their normal siblings. Results showed that Ames dwarf mice did not experience an age-related decline in locomotor activity when compared to their young counterparts. Furthermore, old dwarf mice did not differ from the young groups in inhibitory avoidance retention, while old normal animals performed more poorly than both young groups on this test. Elevated plus-maze behavior did not differ in the old normal versus dwarf groups, but the old groups did differ from the young. Results indicate that both old groups experienced a significant decline in anxiety with age. Taken together, these results indicate that multiple hormone deficiencies resulting from a lack of primary pituitary function have beneficial effects on cognitive function and locomotor behavior in advanced age. In fact, the Ames dwarf mouse may provide a model for studies of delayed mental as well as physical aging.     

Reversal of Aging and Chronic Ethanol-induced Cognitive Dysfunction by Quercetin a Bioflavonoid

Cognitive dysfunction, one of the most striking age-related impairments seen in human beings, has been correlated to the vulnerability of the brain to increased oxidative stress during aging process. Quercetin is a bioflavonoid with strong antioxidant properties. Experiments were performed to study the possible effects of quercetin on cognitive performance of young, aged or ethanol-intoxicated mice (an animal model for cognition dysfunction) using one trail step down type of passive avoidance and elevated plus maze tasks, respectively. Aged or chronic ethanol-treated mice showed poor retention of memory in step-down passive avoidance and in elevated plus-maze task. Chronic administration of quercetin (10, 25 and 50 mg/kg) for 30 days or its co-administration with ethanol (15% w/v, 2 g/kg per orally) for 24 days significantly reversed the age-related or chronic ethanol-induced retention deficits in both the test paradigms. However, in both memory paradigms chronic administration of quercetin failed to modulate the retention performance of young mice. Chronic quercetin administration for 30 days also reversed age associated increase in TBARS levels and decline in forebrain total glutathione (GSH), SOD and catalase levels. Chronic ethanol administration to young mice produced an increase in lipid peroxidation, and a decline in forebrain total glutathione (GSH), SOD and catalase levels, which was significantly reversed by the co-administration of quercetin (10, 25 and 50 mg/kg). The results of the present study showed that chronic quercetin treatment reverses cognitive deficits in aged and ethanol-intoxicated mice, which is associated with its antioxidant property.     

Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin a bioflavonoid

Cognitive dysfunction, one of the most striking age-related impairments seen in human beings, has been correlated to the vulnerability of the brain to increased oxidative stress during aging process. Quercetin is a bioflavonoid with strong antioxidant properties. Experiments were performed to study the possible effects of quercetin on cognitive performance of young, aged or ethanol-intoxicated mice (an animal model for cognition dysfunction) using one trail step down type of passive avoidance and elevated plus maze tasks, respectively. Aged or chronic ethanol-treated mice showed poor retention of memory in step-down passive avoidance and in elevated plus-maze task. Chronic administration of quercetin (10, 25 and 50 mg/kg) for 30 days or its co-administration with ethanol (15% w/v, 2 g/kg per orally) for 24 days significantly reversed the age-related or chronic ethanol-induced retention deficits in both the test paradigms. However, in both memory paradigms chronic administration of quercetin failed to modulate the retention performance of young mice. Chronic quercetin administration for 30 days also reversed age associated increase in TBARS levels and decline in forebrain total glutathione (GSH), SOD and catalase levels. Chronic ethanol administration to young mice produced an increase in lipid peroxidation, and a decline in forebrain total glutathione (GSH), SOD and catalase levels, which was significantly reversed by the co-administration of quercetin (10, 25 and 50 mg/kg). The results of the present study showed that chronic quercetin treatment reverses cognitive deficits in aged and ethanol-intoxicated mice, which is associated with its antioxidant property.     

Unexpected Dual Task Benefits on Cycling in Parkinson Disease and Healthy Adults: A Neuro-Behavioral Model

BackgroundWhen performing two tasks at once, a dual task, performance on one or both tasks typically suffers. People with Parkinson’s disease (PD) usually experience larger dual task decrements on motor tasks than healthy older adults (HOA). Our objective was to investigate the decrements in cycling caused by performing cognitive tasks with a range of difficulty in people with PD and HOAs.MethodsTwenty-eight participants with Parkinson’s disease and 20 healthy older adults completed a baseline cycling task with no secondary tasks and then completed dual task cycling while performing 12 tasks from six cognitive domains representing a wide range of difficulty.ResultsCycling was faster during dual task conditions than at baseline, and was significantly faster for six tasks (all p<.02) across both groups. Cycling speed improved the most during the easiest cognitive tasks, and cognitive performance was largely unaffected. Cycling improvement was predicted by task difficulty (p<.001). People with Parkinson’s disease cycled slower (p<.03) and showed reduced dual task benefits (p<.01) than healthy older adults.ConclusionsUnexpectedly, participants’ motor performance improved during cognitive dual tasks, which cannot be explained in current models of dual task performance. To account for these findings, we propose a model integrating dual task and acute exercise approaches which posits that cognitive arousal during dual tasks increases resources to facilitate motor and cognitive performance, which is subsequently modulated by motor and cognitive task difficulty. This model can explain both the improvement observed on dual tasks in the current study and more typical dual task findings in other studies.     

Shortened seasonal photoperiodic cycles accelerate aging of the diurnal and circadian locomotor activity rhythms in a primate

The gray mouse lemur (Microcebus murinus), a prosimian primate, exhibits seasonal rhythms strictly controlled by photoperiodic variations. Previous studies indicated that longevity can be altered by long-term acceleration of seasonal rhythms, providing a model for assessing various aspects of aging. To assess the effect of aging and accelerated aging on the circadian system of this primate, we compared the circadian rhythm of the locomotor activity in adult mouse lemurs (2-4.5 years, n = 9), aged mouse lemurs (5-9 years, n = 10), and adult mouse lemurs that had been exposed from birth to a shortened seasonal photoperiodic cycle (2-4.5 years, n = 7). Compared to adult animals, aged mouse lemurs showed a significant increase in intradaily variability and an advanced activity onset. Aging was characterized by a decrease in amplitude, with both a decrease in nocturnal activity and an increase in daytime activity. When maintained in constant dim red light, aged animals exhibited a shortening of the free-running period (22.8 +/- 0.1 h) compared to adult animals (23.5 +/- 0.1 h). A 3- to 5-year exposure to an accelerated seasonal photoperiodic rhythm ("annual" duration of 5 months) in accelerated mouse lemurs produced disturbances of the locomotor activity rhythm that resembled those of aged mouse lemurs, whether animals were studied in entrained or in free-running conditions. The present study demonstrated a weakened and fragmented locomotor activity rhythm during normal aging in this primate. Increasing the number of expressed seasonal cycles accelerated aging of parameters related to circadian rhythmicity in adult animals.     

Cognitive Experience and Its Effect on Age-Dependent Cognitive Decline in Beagle Dogs

Test-sophisticated beagle dogs show marked age sensitivity in a size discrimination learning task, with old and senior dogs performing significantly more poorly than young dogs. By contrast, age differences in learning were not seen in dogs naïve with respect to neuropsychological test experience. These results indicate that old animals benefit less from prior cognitive experience than young animals, which is an example of an age-dependent loss in plasticity. This finding also suggests that behaviorally experienced animals are a more useful model of human cognitive aging than behaviorally naïve animals. We also looked at the effect of a program of behavioral enrichment in aged dogs. One year of enrichment did not lead to significant differences, but after 2 years the behaviorally enriched group performed significantly better than the control group. The effect after 2 years indicates that a prolonged program of cognitive enrichment can serve as an effective intervention in aged dogs. These findings demonstrate that cognitive abilities in aged animals can be modified by providing behavioral experience, indicating that cognitive abilities remain moderately plastic, even in very old animals.     

Genetic context drives age-related disparities in synaptic maintenance and structure across cortical and hippocampal neuronal circuits

The disconnection of neuronal circuitry through synaptic loss is presumed to be a major driver of age-related cognitive decline. Age-related cognitive decline is heterogeneous, yet whether genetic mechanisms differentiate successful from unsuccessful cognitive decline through maintenance or vulnerability of synaptic connections remains unknown. Previous work using rodent and primate models leveraged various techniques to imply that age-related synaptic loss is widespread on pyramidal cells in prefrontal cortex (PFC) circuits but absent on those in area CA1 of the hippocampus. Here, we examined the effect of aging on synapses on projection neurons forming a hippocampal-cortico-thalamic circuit important for spatial working memory tasks from two genetically distinct mouse strains that exhibit susceptibility (C57BL/6J) or resistance (PWK/PhJ) to cognitive decline during aging. Across both strains, synapse density on CA1-to-PFC projection neurons appeared completely intact with age. In contrast, we found synapse loss on PFC-to-nucleus reuniens (RE) projection neurons from aged C57BL/6J but not PWK/PhJ mice. Moreover, synapses from aged PWK/PhJ mice but not from C57BL/6J exhibited altered morphologies that suggest increased efficiency to drive depolarization in the parent dendrite. Our findings suggest resistance to age-related cognitive decline results in part by age-related synaptic adaptations, and identification of these mechanisms in PWK/PhJ mice could uncover new therapeutic targets for promoting successful cognitive aging and extending human health span.     

Age-related deficits in neuronal physiology and cognitive function are recapitulated in young mice overexpressing the L-type calcium channel,CaV1.3

The calcium dysregulation hypothesis of brain aging posits that an age-related increase in neuronal calcium concentration is responsible for alterations in a variety of cellular processes that ultimately result in learning and memory deficits in aged individuals. We previously generated a novel transgenic mouse line, in which expression of the L-type voltage-gated calcium, Ca_V1.3, is increased by ~50% over wild-type littermates. Here, we show that, in young mice, this increase is sufficient to drive changes in neuronal physiology and cognitive function similar to those observed in aged animals. Specifically, there is an increase in the magnitude of the postburst afterhyperpolarization, a deficit in spatial learning and memory (assessed by the Morris water maze), a deficit in recognition memory (assessed in novel object recognition), and an overgeneralization of fear to novel contexts (assessed by contextual fear conditioning). While overexpression of Ca_V1.3 recapitulated these key aspects of brain aging, it did not produce alterations in action potential firing rates, basal synaptic communication, or spine number/density. Taken together, these results suggest that increased expression of Ca_V1.3 in the aged brain is a crucial factor that acts in concert with age-related changes in other processes to produce the full complement of structural, functional, and behavioral outcomes that are characteristic of aged animals.     

Age‐Related Effects on the Biological Clock and its Behavioral Output in a Primate

In humans, activity rhythms become fragmented and attenuated in the elderly. This suggests an alteration of the circadian system per se that could in turn affect the expression of biological rhythms. In primates, very few studies have analyzed the effect of aging on the circadian system. The mouse lemur provides a unique model of aging in non‐human primates. To assess the effect of aging on the circadian system of this primate, we recorded the circadian and daily rhythms of locomotor activity of mouse lemurs of various ages. We also examined age‐related changes in the daily rhythm of immunoreactivities for vasoactive intestinal polypeptide (VIP) and arginine‐vasopressin (AVP) in suprachiasmatic nucleus neurons (SCN), two major peptides of the biological clock. Compared to adult animals, aged mouse lemurs showed a significant increase in daytime activity and an advanced activity onset. Moreover, when maintained in constant dim red light, aged animals exhibited a shortening of the free‐running period compared to adult animals. In adults, AVP immunoreactivity (ir) peaked during the second part of the day, and VIP ir peaked during the night. In aged mouse lemurs, the peaks of AVP ir and VIP ir were significantly shifted with no change in amplitude. AVP ir was most intense at the beginning of the night; whereas, VIP ir peaked at the beginning of the daytime. A weakened oscillator could account for the rhythmic disorders often observed in the elderly. Changes in the daily rhythms of AVP ir and VIP ir may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby modify the expression of some biological rhythms.     

Micro-MRI Study of Cerebral Aging: Ex Vivo Detection of Hippocampal Subfield Reorganization,Microhemorrhages and Amyloid Plaques in Mouse Lemur Primates

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.