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PubMed2003

Melatonin and methimazole mimic short-day-induced fattening in gray mouse lemurs.

Short-day-induced fattening was investigated in the small nocturnal primate Microcebus murinus. Animals were either transferred from long photoperiod (LP) to short photoperiod (SP) or maintained in LP and submitted to various treatments. Animals fed daily on 40 microg of melatonin (MEL) at two different times showed a significant increase in body mass compared to LP-exposed animals. This weight gain was more marked in animals fed with MEL 2 h before night onset, suggesting a critical period around the first hours of the night. The MEL-induced fattening was associated with an increase in food intake and a decrease in plasma thyroxin (T4) levels. On the other hand, a decrease in T4 plasma levels induced by two doses of methimazole (MET) led to either an increase (3 mg/day) or a decrease (10 mg/day) of body mass, suggesting a role of thyroid hormones in the photoperiodic regulation of body mass. The MET-induced fattening did not involve any change in food intake. These findings suggest that autumn fattening in the gray mouse lemur proceeds from two distinct mechanisms. First, an increase of food intake may result in the SP-induced increase in MEL secretion. Second, a decrease of energy expenditure may be due to the MEL-induced hypothyroidism.

Adipose Tissue↗
PubMed1997

Effect of vomeronasal organ removal on male socio-sexual responses to female in a prosimian primate (Microcebus murinus).

In most mammals, olfactory cues play an important role in regulating socio-sexual behaviors, but the relative contributions of the main olfactory system and the vomeronasal system remain unclear. The lesser mouse lemur, a nocturnal prosimian, possesses well-developed chemosensory structures, including a functional vomeronasal organ (VNO). In this primitive primate, social communication and competition between males for priority access to receptive females includes reliance on urinary chemical cues. To assess the role of the VNO in mediating males' behavioural responses to females, sexually-experienced intact males (C, n = 8) or males deprived of their VNO (VNX, n = 8) were put in pairs and their socio-sexual behaviors in response to a preoestrous female were monitored. Independent of social context (with or without female), VNX males exhibited less sniffing behaviors than C males, but their marking behaviors, although reduced, were not significantly different. Removal of the VNO dramatically reduced the frequency of both sexual behaviors (anogenital investigations, mounts) and intermale aggressive behaviors. However, VNO removal did not impair successful mating and had no effect on plasma testosterone levels. Lastly, VNX males always exhibited a significantly lower general activity level than C males. The decrease in sexual behaviors and the lack of aggressive intermale competition in responses to a preoestrous female possibly proceed from functional disturbances of central nervous areas connected to the vomeronasal system rather than from a chemosensory deficit per se.

Aggression↗
PubMed1998

Age-related effects on reproductive function and sexual competition in the male prosimian primate, Microcebus murinus.

In the male lesser mouse lemur (Microcebus murinus), a polygamous long-day breeder of which the life span may reach 12-14 years, the effects of aging on socio-sexual relationships were studied on 44 captive animals of various ages. In this primate, new dominance relationships must be established at the beginning of each breeding season. During the breeding season induced by exposure to artificial long days, preoestrous females were introduced into cages of paired males to elicit sexual competition. Sexual behaviors, social interactions through chemical signals, and dominance relationships were recorded in paired males either of similar age (young or aged pairs), or of mixed ages. In all pairs, competition for priority access to females always occurred and dominance relationships were established unrelated to body weight. Although aged animals exhibited significantly less number of sexual and aggressive behaviors, they outranked younger males excepted when reaching oldest age. Independent of male's age, the typical pattern of seasonal rhythm of testosterone was observed, but aged males demonstrated a significant reduction in mean hormonal levels (25.5 +/- 2.8 ng/mL, n = 8) compared to young animals (50 +/- 2.7 ng/mL, n = 8). Moreover, their hormonal response to photoperiod was phase-shifted leading to reduced testosterone values when females entered oestrus. Despite the fact that testosterone levels and sexual behaviors decreased with aging in this primate, older males reached a dominant position, increasing thus their reproductive success.

Aging↗
PubMedDate not supplied

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.

Age Factors↗
PubMedDate not supplied

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.

Aging↗
PubMedDate not supplied

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.

Aging↗
PubMed1997

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.

Aging↗
PubMed2001

Artificially accelerated aging by shortened photoperiod alters early gene expression (Fos) in the suprachiasmatic nucleus and sulfatoxymelatonin excretion in a small primate, Microcebus murinus.

In mammals, a number of anatomical and functional changes occur in the circadian timing system with aging. In certain species, aging can be modified by various factors which induce a number of pathological changes. In a small primate, the gray mouse lemur (Microcebus murinus), long-term acceleration of seasonal rhythms by exposing the animals to a shortened photoperiodic regime (up to 2.5 times the natural photoperiodic regime) alters longevity, based on survival curves and morphological changes. This provides a model for challenging the idea that modifications of the circadian pacemaker are related to chronological (years) versus biological (photoperiodic cycles) age. To assess the effect of aging and accelerated aging on the circadian pacemaker of this primate, we measured body weight variations, the daily rhythm in urine 6-sulfatoxymelatonin and the light-induced expression of the immediate early gene (Fos) in the suprachiasmatic nucleus of mouse lemurs that had been exposed to different photoperiodic cycles. Urine samples were collected throughout the day and urine 6-sulfatoxymelatonin levels were measured by radioimmunoassay. Light-induced Fos expression in the suprachiasmatic nucleus was studied by exposing the animals to a 15-min monochromatic pulse of light (500 nm) at saturating or sub-saturating levels of irradiance (10(11) or 10(14) photons/cm(2)/s) during the dark phase. The classical pattern of 6-sulfatoxymelatonin excretion was significantly altered in aged mouse lemurs which failed to show a nocturnal peak. Fos expression following exposure to low levels of irradiance was reduced by 88% in the suprachiasmatic nucleus of aged mouse lemurs. Exposure to higher irradiance levels showed similar results, with a reduction of 66% in Fos expression in the aged animals. Animals subjected to artificially accelerated aging demonstrated the same alterations in melatonin production and Fos response to light as animals that had been maintained in a routine photoperiodic cycle. Our data indicate that there are dramatic changes in melatonin production and in the cellular response to photic input in the suprachiasmatic nucleus of aged mouse lemurs, and that these alterations depend on the number of expressed seasonal cycles rather than on a fixed chronological age. These results provide new insights into the mechanisms underlying artificial accelerated aging at the level of the molecular mechanisms of the biological clock.

Aging↗
PubMed2002

Characterization of calbindin-positive cones in primates.

The aim of this study is to characterize calbindin-positive photoreceptors and their opsin content in the retina of nocturnal prosimians (Microcebus murinus), New World monkeys (Callithrix jacchus), Old World monkeys (Macaca fascicularis), and humans. To identify the calbindin and opsin content of cones, combined multiple labeling with different fluorescent probes, antibodies directed against calbindin, short, and mid-long wavelength opsins, and lectin peanut agglutinin cytochemistry were used. With the exception of Microcebus, calbindin is present in the cones of all primates but is absent from rods. The distribution of calbindin is similar in human and macaque cones, with dense label in the inner segment, cell body, axon and cone pedicle. Cones in marmoset also show dense staining in the cell body, axon and pedicle but only light label in the inner segment. Primate cone outer segments do not contain calbindin. In the primates studied, three patterns of calbindin and opsin localization are observed. In macaque and marmoset all short and mid-long wavelength cones contain calbindin. In humans, all mid-long wavelength cones contain calbindin whereas all short wavelength cones are devoid of calbindin as confirmed by confocal microscopy. In the nocturnal prosimian Microcebus none of the mid-long or short wavelength cones contain calbindin. In addition to primates, calbindin is absent in cones of other nocturnal species but is present in cones of diurnal species suggesting a difference in the role of calbindin possibly related to the adaptational states or other photoreceptor properties.

Adult↗
PubMed1998

A stereotaxic atlas of the grey lesser mouse lemur brain (Microcebus murinus).

In response to the growing interest in the prosimian Microcebus murinus for studies on cerebral aging, the stereotaxic atlas of its brain was carried out in view of further anatomical, biochemical, electrophysiological, and behavioral investigations as well as for therapeutic experiments. This primate, which could be a valuable model for neuroscientific studies in various domains, presents numerous physiological advantages (e.g., size, cost, and ability to breed) compared to rodents, which can be used as nonprimate models, and simians. The atlas, valid for adult microcebes of every age and both sexes, consists of 54 frontal plates and 28 sagittal plates. For the establishment of stereotaxic coordinates and for drawings and photographs, 10 adult specimens of Microcebus murinus were used. The brains were frozen, cut into sections of 50 microm thickness, every fourth section being stained with Nissl. First, sections were projected and the outlines of the different structures, nuclei, and fibers were drawn. Then, the accuracy of the analysis was improved by detailed observation directly by microscope and also by computer analysis. Finally, the photographs of the sections were scanned and processed using the software Photoshop and Illustrator. For testing coordinates, several verifications were made. Experiments on lesions and injections of different substances were carried out in specific regions of the brain and brains implanted with needles were fixed in formol and embedded in paraffin wax.

Anatomy, Artistic↗
PubMed2003

Physical activity and balance performance as a function of age in a prosimian primate (Microcebus murinus).

Physical activity and balance performance were examined in gray mouse lemurs (Microcebus murinus) aging from 1 to 10 years of age. Home cage spontaneous activity, physical and behavioral activities in an open-field test and balance performance at the Rotarod test were evaluated. In this prosimian primate, which life span reaches 8-10 years in captivity, balance performance at the Rotarod test showed a clear decrease with age. Latency to fall decreased from 154.7+/-13.5s in the youngest group of animals to 31.2+/-5.4s in animals aging 6 years or more. A significant decrease was noticeable as early as 4 years of age. In a familiar cage, locomotor activity and jumping frequency were reduced in aged animals compared to adults. In contrast, when introduced in an open field, aged animals exhibited an increase in locomotor activity and sniffing frequency when compared to younger animals, while latency to first movement was higher in the adult than in the aged subjects. Based on these results, repeated behavioral testing should be initiated early in the life of this species, in association with an evaluation of visual and olfactory capacities. These findings are important to take into account if detailed evaluations of sensory-motor performances are required in studies on aging processes in primates.

Aging↗
PubMed1997

Prion immunoreactivity in brain, tonsil, gastrointestinal epithelial cells, and blood and lymph vessels in lemurian zoo primates with spongiform encephalopathy.

We report on two animals of a non-human primate species Eulemur fulvus mayottensis, housed in the local zoo and fed over a number of years with a food containing cattle meat, that developed serious neurological symptoms associated with prion immunoreactivity in brain and various viscera. Microscopy of the brains showed neuronal vacuolation with patchy/perivacuolar immunolabelling with an abnormal isoform of prion protein (IR-PrP), an important characteristic of spongiform encephalopathy. For the first time, we report the presence in the same severely ill animals of IR-PrP in the gastrointestinal tract, detected by immunocytochemistry with mono- and polyclonal antibodies directed against various parts of the PrP. Strong PrP labelling was observed in the epithelial cells lining the pharyngeal and gastrointestinal lumen. The tonsils and the walls of the lymph and blood vessels below the intestinal epithelium were also labelled. There were no such immunoreactions in healthy lemurians killed as controls, i.e. a younger congener of the same species housed under the same conditions, and others belonging to the smaller species Microcebus murinus, reared in the laboratory and never fed on commercial food products containing cattle meat. These results demonstrate a strong PrP accumulation in the brain, the gastrointestinal tract and underlying lymphoreticular structures in these primates living in a zoological park and suffering from a spongiform encephalopathy.

Animals↗
PubMed2003

Calpain 3 is expressed in astrocytes of rat and Microcebus brain.

The calcium-dependent protease calpain is involved in numerous functions, including the control of cell survival, plasticity and motility. Whereas the isoforms calpain 1 and 2 have been described as ubiquitously expressed enzymes, calpain 3 has been called "muscle-specific", although trace amounts of calpain 3 mRNA have been detected by Northern blot in brain homogenates. In this study, we validated antibodies raised either against the peptides that were specific for a given isoform or the peptides present in all the three isoforms. We then used the anti-calpain 3 antibodies together with antibodies directed against cell-type-specific proteins to determine by double- and triple-labelling immunocytochemistry if the protease is expressed in specific cell populations of rat as well as lesser mouse lemur (Microcebus murinus) brain. Calpain 3 was almost exclusively found in cells displaying astrocyte morphology. These cells, most of which co-expressed glial fibrillary acidic protein, were particularly numerous close to the striatal subventricular zone (where numerous neurones forming the rostral migratory stream (RMS) towards the olfactory bulbs are generated) and the RMS itself. Other immunoreactive cells were found close to the pial surface of the forebrain, in the corpus callosum and in the dentate gyrus. Calpain 3 may be involved in astrocyte plasticity and/or motility.

Animals↗
PubMed1998

Influence of daylength on metabolic rate and daily water loss in the male prosimian primate Microcebus murinus.

In its natural habitat, Microcebus murinus, a small malagasy prosimian primate, is exposed to seasonal shortage of water and resources. During the winter dry season, animals enter a pronounced fattening period with concurrent decrease in behavioural/physiological activities, whereas the breeding season is restricted to the rainy summer months. To determine the role of daylength on metabolic rate and water loss in this nocturnal primate, we measured body mass, oxygen consumption at 25 degrees C (RMR), circadian water loss through urine output (UO) and evaporation (EWL) in eight males exposed to either short days (8L:16D SD) or long days (14L:10D LD), under controlled captive conditions. Exposure to SD led to a ponderal increase (maximal body mass: 125 +/- 4 g, N = 8), and to significant changes in RMR and water loss, both reaching lowest values after 3 months under SD (0.84 +/- 0.04 ml O2 h-1 g-1 and 38 +/- 0.3 mg H2O g-1 day-1, respectively). Following exposure to LD, body mass decreased to 77 +/- 3 g (N = 8), whereas both RMR and water loss, mainly through EWL, significantly increased (P < 0.001), the highest value occurring after 2 months (1.51 +/- 0.08 ml O2 h-1 g-1 and 87 +/- 7 mgH2O g-1 day-1, respectively). Moreover, independent of daylength, circadian changes in EWL were characterized by significantly reduced values during the diurnal rest. The results demonstrate that daylength variations affect the physiology of this tropical primate, allowing anticipatory adaptation to seasonal environmental constraints.

Animals↗
PubMed2003

Daily hypothermia in captive grey mouse lemurs (Microcebus murinus): effects of photoperiod and food restriction.

The grey mouse lemur (Microcebus murinus) is a small nocturnal primate exhibiting daily torpor. In constant ambient temperature (22-24 degrees C), body temperature (Tb) and locomotor activity were monitored by telemetry in animals exposed to short (SP: 10 h light/day) or long (LP: 14 light/day) photoperiods. They were first fed ad libitum for 8 days and then subjected to 80% restricted feeding for 8 more days. During ad libitum feeding, locomotor activity was significantly lower in SP-exposed animals than in LP-exposed animals. Whatever the photoperiod, animals entered daily hypothermia within the first hours following the light onset. Depth of daily hypothermia increased irregularly under SP exposure, whereas minimal daily Tb was constantly above 35 degrees C under LP exposure. After the transfer from long photoperiod to short photoperiod corresponding to the induction of seasonal fattening, locomotor activity and depth of controlled daily hypothermia did not change significantly. In contrast, food restriction led to a significant increase in locomotor activity and in frequency of daily torpor (Tb<33 degrees C) and body temperature reached minimum values averaging 25 degrees C. However, SP-exposed animals exhibited lower minimal daily Tb and higher torpor duration than LP exposed animals. Therefore, daily torpor appears as a rapid response to food restriction occurring whatever the photoperiod, although enhanced by short photoperiod.

Animals↗
PubMed2002

BSE infection of the small short-lived primate Microcebus murinus.

Eleven Microcebus murinus (lemur) primates were intracerebrally or orally infected by bovine spongiform encephalopathy (BSE) or macaque-adapted BSE (MBSE) brain homogenates. In many BSE and MBSE infected lemurs, but not in animals inoculated with normal bovine brain, persistent behavioral changes occurred as early as 3 months, and neurological signs as early as 13 months after infection. Immunohistochemical examination of animals sacrificed during the incubation period revealed an abnormal accumulation of 'prion' protein (PrP) in the intestinal wall, intestinal nervous plexus, mesenteric lymph nodes and spleen, and in the clinical stage, also in the brain. In MBSE-inoculated animals, proteinase K resistance of the PrP (PrPres) was confirmed by Western blot in the spleen and the brain. Obvious signs of neurodegeneration were observed in all infected animals characterized by hyperaggregated and paired-helical filaments-immunoreactive Tau proteins, beta 42-amyloid plaques and astrogliosis. Additionally, PrPres was present in the ganglion cells of the retina in diseased animals after either intracerebrally or oral infection by the BSE or MBSE agent. These results show that the microcebe is susceptible to the BSE infectious agent via intracerebral and oral routes with comparatively short incubation periods compared to simians, and could be a useful animal model to study the pathophysiology of disease transmission in primates.

Administration, Oral↗
PubMed2002

Taste thresholds and suprathreshold responses to tannin-rich plant extracts and quinine in a primate species (Microcebus murinus).

Theories of plant chemical defenses discriminate between quantitative digestibility reducers (e.g., tannins) and qualitative toxins (e.g., alkaloids). Since the differential effect on taste of these compounds is poorly known, we recorded ingestive responses of a primate species, Microcebus murinus, to four tannin-rich plant extracts and to quinine, by using the behavioral method of the "two-bottle test." The efficiency of tannic extracts at precipitating protein was measured with the blue BSA method. Inhibition taste thresholds for tannins added to a moderately sweet solution varied between 0.25 and 2 g/l. The threshold for quinine hydrochloride was 0.32 g/l. The profiles of the response/concentration curves established for these astringent and bitter substances were similar, with maximal inhibition of consumption occurring for near-threshold concentrations. The large amounts of quinine required to deter this small-bodied species from feeding were unexpected, given its unspecialized frugivorous/insectivorous diet. We propose that the taste responses of Microcebus to tannins have been shaped in relation to the widespread occurrence of efficient polyphenols in food plants, while low responsiveness to quinine reflects a low risk of ingesting toxic alkaloids when feeding on ripe fruits and insects.

Animals↗