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PubMedDate not supplied

Choline acetyltransferase and somatostatin levels in aged Microcebus murinus brain.

beta-Amyloid protein (beta-AP) deposits, analoguous to those found in Alzheimer's disease (AD) are observed in the brain of aging Microcebus murinus. Because choline acetyltransferase (ChAT) activity and somatostatin (SRIH) content are consistently decreased in AD, we tested whether such changes could be observed in middle aged to aged Microcebus cerebral cortex and whether they were accompanied by beta-AP deposits. A positive correlation was observed between age and ChAT activity. By HPLC, SRIH immunoreactivity eluted as four peaks, two of which being identical with SRIH-28 and SRIH-14 while the other two likely represented precursor forms. Cortical SRIH content was not significantly affected by age. ChAT activity and SRIH content were not significantly correlated. Amyloid angiopathy was observed in every brain examined and the presence of cortical lesions analoguous to senile plaques observed in the oldest case only which did not demonstrate important alterations in ChAT and somatostatin levels.

Aging↗

PubMedDate not supplied

Identification of amyloid beta protein in the brain of the small, short-lived lemurian primate Microcebus murinus.

The deposition of amyloid beta (A beta) protein in the brain has been demonstrated immunocytochemically in the small Lemurian primate Microcebus murinus. Both meningocerebral vascular deposits and cortical parenchymal deposits occur. All eight aged (> 8 years old) Microcebus examined showed vascular amyloid deposits, whereas only four exhibited parenchymal plaques. The vascular amyloid infiltrated the tunica media of the leptomeningeal and cortical arteries and arterioles and was also found in capillaries. A beta was observed to be deposited in three general forms in the cortical neuropil: round or elliptical plaques that were thioflavin-negative but sometimes showed a central concentration of A beta immunoreactivity; round plaques with a densely immunoreactive core that was thioflavin-positive; extensive ribbon-like infiltrations enclosing multiple cortical blood vessels. These observations, taken together with previous descriptions of age-related neurodegenerative changes in Microcebus, indicate that this species undergoes a beta-amyloid-associated neuropathology highly similar to that seen in Alzheimer's disease. We conclude that this lemurian primate of small size and relatively short life expectancy, provides a compelling animal model of some principal features of Alzheimer's disease.

Aging↗

PubMed2005

Gonadotropin-releasing hormone (GnRH) immunoreactive neurons in male mouse lemurs following removal of the vomeronasal organ.

Removal of the vomeronasal organ (VNO) in male mouse lemurs led to an increase in the number of immunoreactive gonadotropin-releasing hormone (GnRH) neurons in the medial preoptic area, compared to control males. No difference was found in the mediobasal hypothalamus. In this primate, which presents a fully functional VNO, the anterior part of the hypothalamus could be the major target for VNO-mediated regulation of GnRH function and the subsequent modulation of chemosensory dependent reproductive behavior.

Animals↗

PubMed2004

Are age-related deficits in balance performance mediated by time of day in a prosimian primate (Microcebus murinus)?

We examined the effects of age and time of day on balance performance in the gray mouse lemur (Microcebus murinus) in relation to body temperature variations. Groups of young, adult and aged animals were entrained to either short (SP, L/D 10/14) or long photoperiod (LP, L/D 14/10) and tested in the accelerating Rotarod at three phases of their light/dark cycle (beginning and end of the light phase, beginning of the dark phase). In addition, for each test, rectal temperature (Tr) was measured. Under LP, whatever the test phase, this primate showed a clear age-related decrease in balance performance. Under SP, no significant age-related decline in balance could be detected. Whatever the photoperiod, an effect of time of day on balance performance could only be seen in adults, with better performances at the beginning of the dark phase when Tr values were higher. Under LP, daily variations of both balance performance and Tr disappeared with advancing age. Consequently, age differences were substantially greater when testing was conducted during the dark phase of the light/dark cycle. The time of day effect on balance performance and the loss of daily variations with age suggest the influence of age-related changes within the biological clock.

Age Factors↗

PubMed2005

Aging and season affect plasma dehydroepiandrosterone sulfate (DHEA-S) levels in a primate.

In humans, plasma concentration of dehydroepiandrosterone sulfate (DHEA-S) declines with age and is considered as a potential predictor of longevity. DHEA-S is apparently unique to primates but few species of nonhuman primates have been studied for age-related changes in DHEA-S. In a short living primate, the grey mouse lemur (longevity 10-13 years), metabolic and physiological parameters exhibit high seasonal changes with age-related decrease in amplitude. From 8 month- to 11-year-old males (N = 175), plasma DHEA-S levels were measured either during the breeding season or during the winter sexual rest. Plasma DHEA-S levels show high significant changes according to season and age. During winter, DHEA-S levels were maintained low and constant over lifetime. During the summer breeding season, a decline of DHEA-S levels occurred after the age of 3 years and accelerated after the age of 6 years. DHEA-S level was about 30-40% of its adult value with age over 6 years, a stepwise pattern most closely resembling to human pattern. In mouse lemur, DHEA-S met the criteria for a biomarker of aging. When correlated to other age-related changes, the results give the opportunity to consider the mouse lemur as a promising primate model to study aging processes.

Aging↗

PubMed2006

Behavioral thermoregulation in a non human primate: effects of age and photoperiod on temperature selection.

Deficits in autonomic thermoregulatory capacities have been identified in aged humans and animals, but little is known about the effect of aging on behavioral thermoregulation and the potential effect of season. Preferred ambient temperature (T(a)) in a thermal gradient (available T(a)s from 10 to 30 degrees C) was measured in the mouse lemur, a nocturnal Malagasy primate. Male mouse lemurs (40 adults and 40 aged) were studied under short (SP, resting season) and long photoperiod (LP, breeding season). Additionally, daily body temperature rhythm was telemetrically recorded in 30 individuals of both age categories. In adults exposed to SP, a choice for warm climates was observed, with a mean diurnal T(a) of 26 degrees C. Day-night differences in selected T(a) occurred only in animals exposed to SP. In LP, selection of a warm environment did not seem to be a necessary factor for maintenance of normothermia. Aged animals selected warmer T(a)s than adults during the night like during the day, whatever the photoperiod. In relation to changes in body temperature rhythm according to age, aged animals would select warmer environments possibly to compensate autonomic deficiencies. Further studies on age-related changes in hormonal and cellular functions involved in energy balance and thermoregulation will help decipher the causes of insufficient responses to thermal stress observed in the elderly.

Aging↗

PubMed2006

Aging affects executive functions and memory in mouse lemur primates.

The decline of cognitive capacities with age in mouse lemur primates (Microcebus murinus) was assessed. Eight young adults (2-4 years) and nine aged adults (7-11 years) were examined on tasks designed to measure executive functions, procedural and declarative memory. The mouse lemurs were tested on the go-no go successive discrimination task, set shifting tasks (including extra-dimensional shift and reversal discrimination) and a spatial rule-guided discrimination task. There were four major findings. First, the deficits observed were not global but only on specific tasks indicating that only specific cognitive abilities are impaired with aging. Second, there were variations among aged subjects suggesting different patterns of cognitive aging. Third, alterations in cognitive abilities with aging in mouse lemurs seemed to be comparable to those described in aged monkeys and humans. Indeed, executive functions and declarative memory were affected in subpopulations of aged subjects whereas procedural memory remained intact in all the tested aged subjects. Finally, two forms of executive dysfunctions were distinguished among the aged subjects. The ultimate goal is to correlate age-related cognitive deficit with brain alterations and this study has helped to select candidate regions to be thoroughly scrutinized in aged mouse lemurs.

Aging↗

PubMed2004

Substrate alters forelimb to hindlimb peak force ratios in primates.

It is often claimed that the walking gaits of primates are unusual because, unlike most other mammals, primates appear to have higher vertical peak ground reaction forces on their hindlimbs than on their forelimbs. Many researchers have argued that this pattern of ground reaction force distribution is part of a general adaptation to arboreal locomotion. This argument is frequently used to support models of primate locomotor evolution. Unfortunately, little is known about the force distribution patterns of primates walking on arboreal supports, nor do we completely understand the mechanisms that regulate weight distribution in primates. We collected vertical peak force data for seven species of primates walking quadrupedally on instrumented terrestrial and arboreal supports. Our results show that, when walking on arboreal vs. terrestrial substrates, primates generally have lower vertical peak forces on both limbs but the difference is most extreme for the forelimb. We found that force reduction occurs primarily by decreasing forelimb and, to a lesser extent, hindlimb stiffness. As a result, on arboreal supports, primates experience significantly greater functional differentiation of the forelimb and hindlimb than on the ground. These data support long-standing theories that arboreal locomotion was a critical factor in the differentiation of the forelimbs and hindlimbs in primates. This change in functional role of the forelimb may have played a critical role in the origin of primates and facilitated the evolution of more specialized locomotor behaviors.

Animals↗

PubMed2006

Kinematics of vertical climbing in lorises and Cheirogaleus medius.

The type of climbing exhibited by apes and atelines is argued to have been important in the evolution of specialized locomotion, such as suspensory locomotion and bipedalism. However, little is known about the mechanics of climbing in primates. Previous work shows that Asian apes and atelines use larger joint excursions and longer strides than African apes and the Japanese macaque, respectively. This study expands knowledge of climbing mechanics by providing the first quantitative kinematic data for vertical climbing in four prosimian species: three lorisid species (Loris tardigradus, Nycticebus coucang, and Nycticebus pygmaeus) that share with apes and atelines morphological traits arguably related to climbing, and a more generalized quadruped, Cheirogaleus medius. Subjects were videotaped as they climbed up a wooden pole. Kinematic values, such as step length and limb excursions, were calculated and compared between species. The results of this study show that lorises, like Asian apes and spider monkeys, use relatively larger joint excursions and longer steps than does C. medius during climbing. These data lend further support to the idea that some primate species (e.g., lorises, atelines, and apes) are more specialized kinematically and morphologically for climbing than others. Pilot data suggest that such kinematic differences in climbing style across broad phylogenetic groups may relate to the energetics of climbing. Such data may be important for understanding the morphological and kinematic adaptations to climbing exhibited by some primates.

Adaptation, Physiological↗

PubMed2005

Age effect on olfactory discrimination in a non-human primate, Microcebus murinus.

In order to characterize age-related cognitive changes, olfactory discrimination was assessed in Microcebus murinus, a prosimian primate. We compared young (n = 10) and old (n = 8) animals for individual performance on three olfactory tasks. Animals had to perform a detection, a transfer, and a reversal learning task using a go, no go conditioning procedure. No differences were observed between the two groups, indicating that aging is not inevitably associated with a decline in cognitive function. We did, however, observe two aged animals showing altered behavior. One animal displayed impairments in the reversal learning task, and the other showed impairments in both the transfer and reversal tasks. Transfer impairment may be due to a hippocampal alteration, whereas the perseverative tendency noted in the reversal task may be associated with frontal lobe dysfunction. Because some aged M. murinus display lesions that are pathognomonic of Alzheimer's disease, our observations highlight its potential utility as a primate model for studying cognitive deficits in relation to age and associated pathologies.

Aging↗

PubMed2005

Redistribution of CB1 cannabinoid receptors during evolution of cholinergic basal forebrain territories and their cortical projection areas: a comparison between the gray mouse lemur (Microcebus murinus, primates) and rat.

Endocannabinoid signaling, mediated by presynaptic CB1 cannabinoid receptors on neurons, is fundamental for the maintenance of synaptic plasticity by modulating neurotransmitter release from axon terminals. In the rodent basal forebrain, CB1 cannabinoid receptor-like immunoreactivity is only harbored by a subpopulation of cholinergic projection neurons. However, endocannabinoid control of cholinergic output from the substantia innominata, coincident target innervation of cholinergic and CB1 cannabinoid receptor-containing afferents, and cholinergic regulation of endocannabinoid synthesis in the hippocampus suggest a significant cholinergic-endocannabinergic interplay. Given the functional importance of the cholinergic modulation of endocannabinoid signaling, here we studied CB1 cannabinoid receptor distribution in cholinergic basal forebrain territories and their cortical projection areas in a prosimian primate, the gray mouse lemur. Perisomatic CB1 cannabinoid receptor immunoreactivity was unequivocally present in non-cholinergic neurons of the olfactory tubercule, and in cholecystokinin-containing interneurons in layers 2/3 of the neocortex. Significantly, CB1 cannabinoid receptor-like immunoreactivity was localized to cholinergic perikarya in the magnocellular basal nucleus. However, cortical cholinergic terminals lacked detectable CB1 cannabinoid receptor levels. A dichotomy of CB1 cannabinoid receptor distribution in frontal (suprasylvian) and parietotemporal (subsylvian) cortices was apparent. In the frontal cortex, CB1 cannabinoid receptor-containing axons concentrated in layers 2/3 and layer 6, while layer 4 and layer 5 were essentially devoid of CB1 cannabinoid receptor immunoreactivity. In contrast, CB1 cannabinoid receptors decorated axons in all layers of the parietotemporal cortex with peak densities in layer 2 and layer 4. In the hippocampus, CB1 cannabinoid receptor-containing terminals concentrated around pyramidal cell somata and proximal dendrites in the CA1-CA3 areas, and granule cell dendrites in the molecular layer of the dentate gyrus. CB1 cannabinoid receptors frequently localized to inhibitory GABAergic terminals while leaving glutamatergic boutons unlabeled. Aging did not affect either the density or layer-specific distribution of CB1 cannabinoid receptor-immunoreactive processes. We concluded that organizing principles of CB1 cannabinoid receptor-containing neurons and their terminal fields within the basal forebrain are evolutionarily conserved between rodents and prosimian primates. In contrast, the areal expansion and cytoarchitectonic differentiation of neocortical subfields in primates is associated with differential cortical patterning of CB1 cannabinoid receptor-containing subcortical and intracortical afferents.

Acetylcholine↗

PubMed2004

Response to urinary volatiles and chemosensory function decline with age in a prosimian primate.

The age-related decline in olfaction is well documented in humans. However, no data are available to date on changes in olfactory sensitivity with age in nonhuman primates. In the male gray mouse lemur (Microcebus murinus), a prosimian primate, the sense of smell is of high relevance for the modulation of both behavioral and physiological functions. We first assessed the effect of aging on physiological responses to urinary cues by measuring reproductive function in adult and aged males exposed to urine odor of preoestrous females. We then evaluated the effect of aging on chemosensory function using a discrimination test in freely behaving animals. Our results indicate that whereas adult animals show a clear increase in testosterone levels when exposed to female urine odor, this effect is lacking in aged animals. In addition, chemosensory function shows a progressive decline with age. Using both physiological responses to urinary volatiles and spontaneous behavior, this study provides the first data set on the effect of aging on chemosensory responsiveness in a nonhuman primate.

Aging↗

PubMed2004

Odor discrimination assessment with an automated olfactometric method in a prosimian primate, Microcebus murinus.

The present study was aimed at adapting an automated olfactometer designed for use with rodents to a nocturnal lemur Microcebus murinus. This apparatus allows rigorous control of odor stimuli. We show that M. murinus could remain quiet and attentive for about 20 min in the test chamber, allowing daily sessions of 40 consecutive trials. This allowed us to train M. murinus subjects to learn a go/no-go discrimination procedure using fruity-odor cues. Each of seven subjects reached or exceeded a criterion of 33 correct responses in a block of 40 trials in a range of 4-14 training sessions. When trained on an odor reversal task, performance initially dropped sharply, followed by rapid acquisition of the new task. These outcomes demonstrate that, like rodents, M. murinus can be trained using operant conditioning in an automated olfactometer. This species should prove useful for investigating cognitive capacities and neurodegenerative disease in a primitive primate model.

Animals↗

PubMed2004

Changes in olfactory inputs modify the energy balance response to short days in male gray mouse lemurs.

The role of olfaction/olfactory cues on photoperiodic responses was assessed in Malagasy primate, the gray mouse lemur. When exposed to short photoperiod (SP), this primate demonstrates rapid changes in energy balance as adaptive anticipatory response for winter survival. To follow early changes induced by SP exposure, body mass, food intake, resting metabolism (RMR) and free thyroxin levels in plasma (T4) were measured in males abruptly transferred to SP: six intact males (controls), eight males that underwent bilateral olfactory removal (BOX) and eight males exposed to male urinary cues (U-exposed). To assess the effect of SP exposure, two other groups were maintained for 6 weeks under LP: six controls and six BOX males. Whereas all studied parameters remained constant in controls and BOX males maintained under LP, exposure to SP led to different responses according to groups. In controls, SP exposure led to a regular increase in body mass and after 4 weeks under SP, plasma T4 levels, food consumption and RMR significantly decreased. Even if BOX males demonstrated hyperphagic patterns regardless of the photoperiod, an increase in body mass was also induced by SP exposure but without changes in RMR or food intake that were body mass-dependent. In U-exposed males, body mass gain was significantly reduced while food intake and RMR remained high. In both BOX and U-exposed males, SP exposure led to a transient but high increase in T4 levels compared to controls. These results suggest that olfaction/olfactory cues may delay the SP-mediated changes in energy balance.

Adaptation, Physiological↗

PubMed2005

Social inhibition of seasonal fattening in wild and captive gray mouse lemurs.

Due to their differential reproductive investment, males and females often exhibit high differences in energy management. The main hypothesis tested in this study is that short photoperiod-induced fattening in the small primate Microcebus murinus is strongly affected by social cues. Short photoperiod-induced changes in body mass, lean mass and thyroid hormone T4 plasma levels measurements were investigated in wild and captive animals. Individual housing showed that both males and females are able to fatten. Fattening was associated with a slight increase of lean mass that reached a plateau after 3 weeks. In contrast, social grouping led to an inhibition of fattening, even when direct interactions were prevented. This social inhibition was mainly observed in males, especially when housed with females, suggesting that their low weight gain in the wild is due to female dominance. Accordingly, wild and captive animals of both sexes exhibited a decrease in T4 plasma levels, revealing a decrease in energy expenditure. Moreover, testis recrudescence observed after 20 weeks of short photoperiod exposure did not lead to any inhibition of fattening, indicating that males take advantage of female hibernation late in the dry season to fatten and use their fat reserves for the mating competition. Therefore, seasonal fattening may be used by females to prepare for hibernation and by males to prepare for the mating competition.

Analysis of Variance↗

PubMed2006

The ever-increasing diversity in mouse lemurs: three new species in north and northwestern Madagascar.

Mouse lemurs (Microcebus spp.) are the world's smallest primates and endemic to Madagascar. Several recent taxonomic revisions resulted in an extraordinary increase of recognized species. What still was considered as being two species at the beginning of the 20th century is currently recognized as 12 taxa. Based on fur coloration pattern, they can be divided into grayish and reddish forms. Two major models have been proposed to explain the extensive speciation events in the Malagasy fauna. The best known suggests that major rivers and mountains combine to act as effective barriers to gene flow and thereby facilitate allopatric speciation processes. A more recent model used an analysis of watersheds in the context of Quaternary climatic shifts to explain the process of explosive speciation on the island. We tested these two models by covering the areas between all major rivers (n=8) in northwestern and northern Madagascar. Mouse lemurs were systematically caught, sampled and morphometrically characterized in 25 sites (with 2-49 individuals per site and species). A complete phylogeny was constructed on the basis of the sequences of three mitochondrial loci (in total 1296 bp). The phylogenetic data revealed a previously unknown biodiversity with three new mouse lemur species among the reddish forms, each having a very small distribution, i.e., being restricted to only one Inter-River-System (IRS). Morphometric analyses underlined their distinctiveness and a brief formal species description is provided. In contrast to the reddish forms, grayish forms have a very low species diversity coupled with broad distributions that cover more than one IRS. These differences among the species are discussed as outcome of divergent colonization scenarios. Elements of both biogeographic models are combined in a new hypothesis that aims to explain the speciation process leading to the present distribution of mouse lemurs in Madagascar.

Analysis of Variance↗

PubMed1999

Magnetic resonance microscopy of iron in the basal forebrain cholinergic structures of the aged mouse lemur.

Increased non-heme iron levels in the brain of Alzheimer's disease (AD) patients are higher than the levels observed in age matched normal subjects. Iron level in structures that are highly relevant for AD, such as the basal forebrain, can be detected post mortem with histochemistry. Because of the small size of these structures, in vivo MR detection is very difficult at conventional field magnets (1.5 and 4 T). In this study, we observed iron deposits with histochemistry and MR microscopy at 11.7 T in the brain of the mouse lemur, a strepsirhine primate which is the only known animal model of aging presenting both senile plaques and neurofibrillary degeneration. We also examined a related species, the dwarf lemur. Iron distribution in aged animals (8 to 15 years old) agrees with previous findings in humans. In addition, the high iron levels of the globus pallidus is paralleled by a comparable contrast in basal forebrain cholinergic structures. Because of the enhancement of iron-dependent contrast with increasing field strength, microscopic magnetic resonance imaging of the mouse lemur appears to be an ideal model system for studying in vivo iron changes in the basal forebrain in relation to aging and neurodegeneration.

Animals↗

PubMedDate not supplied

Photoperiod-induced changes in energy balance in gray mouse lemurs.

To cope with the 6-month dry winter occurring in its natural habitat, the gray mouse lemur (Microcebus murinus), a Malagasy prosimian primate, exhibits a pre-wintering fattening phase that has been previously demonstrated to be dependent on the photoperiod. To assess early changes in energy balance following a photoperiodic shift, food intake (FI), resting metabolic rate (RMR), plasma triglycerides, plasma thyroxine and urinary excretion of cortisol were measured in 12 males and 12 females for 8 weeks following a shift from short (SP: 10 h light/day) to long (LP: 14 h light/day) photoperiod or from LP to SP. Shift from LP to SP led to a high, linear body mass (BM) increase in both sexes, concomitant to an increase in plasma triglycerides and a decrease in plasma thyroxine, while no change in RMR occurred. FI significantly increased from 30 to 40 kcal/day as early as the first week following SP exposure but spontaneously decreased after 4 weeks, reaching minimal values (10 kcal/day) after 14 weeks of SP exposure. Shift from SP to LP led to a decrease in BM and an increase in FI, but both were slow and different between males and females. No change in RMR was observed except a significant increase in males during the first week of LP exposure. However, plasma thyroxine levels and cortisol excretion similarly increased in both sexes following LP exposure. These results suggest that autumnal fattening mainly proceed from changes in FI and in thyroxine secretion triggered by exposure to SP. In contrast, BM loss following LP exposure would be related to seasonal sexual activation rather than to a direct control by photoperiod.

Animals↗