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PubMed1997

Change in photoperiodic cycle affects life span in a prosimian primate (Microcebus murinus).

The lesser mouse lemur, a small prosimian primate, exhibits seasonal rhythms strictly controlled by photoperiodic variations. Exposure to day lengths shorter than 12 h results in complete sexual rest, fattening, lethargy, and reduced behavioral activities; whereas exposure to day lengths greater than 12 h induces sexual activity, an increase in behavioral activities, and high hormonal levels. The objective of this study was to test whether long-term acceleration of seasonal rhythms may affect survival and longevity of this primate. In captivity, acceleration of seasonal rhythms was obtained by exposing the animals to an accelerated photoperiodic regimen consisting of 5 months of long photoperiod followed by 3 months of short photoperiod. The age-specific survival rate in animals exposed from birth to accelerated photoperiodic conditions (n = 89) was compared to the age-specific survival rate of animals maintained under a natural photoperiod (n = 68). Independent of sexes, the mean life span (45.5 +/- 2.1 months) and maximal survival (79.3 +/- 3.3 months) were significantly (p < .01) shortened in mouse lemurs exposed to the accelerated photoperiodic cycle compared to those in animals living under annual photoperiod (63.2 +/- 2.5 and 98 +/- 3.9 months for mean life span and maximal survival, respectively). This reduction of about 30% of life span was not accompanied by a desynchronization of biological rhythms under photoperiodic control and was not related to an increase in reproduction or in duration of time spent in active conditions. However, when the number of seasonal cycles experienced by 1 individual is considered rather than chronological age, the mean life span was 5 seasonal cycles and maximum survival reached 9-10 cycles, independent of sex or of photoperiodic regimen. These results suggest that in mouse lemurs, as in other seasonal mammals, longevity may depend on the expression of a fixed number of seasonal cycles rather than on a fixed biological age.

Aging↗
PubMed2006

Incongruence between genetic and morphological diversity in Microcebus griseorufus of Beza Mahafaly.

BACKGROUND: The past decade has seen a remarkable increase in the number of recognized mouse lemur species (genus Microcebus). As recently as 1994, only two species of mouse lemur were recognized according to the rules of zoological nomenclature. That number has now climbed to as many as fifteen proposed species. Indeed, increases in recognized species diversity have also characterized other nocturnal primates--galagos, sportive lemurs, and tarsiers. Presumably, the movement relates more to a previous lack of information than it does to any recent proclivity for taxonomic splitting. Due to their nocturnal habits, one can hypothesize that mouse lemurs will show only minimal variation in pelage coloration as such variation should be inconsequential for the purposes of mate and/or species recognition. Even so, current species descriptions for nocturnal strepsirrhines place a good deal of emphasis on relatively fine distinctions in pelage coloration. RESULTS: Here, we report results from a multi-year study of mouse lemur populations from Beza Mahafaly in southern Madagascar. On the basis of morphological and pelage variation, we initially hypothesized the presence of up to three species of mouse lemurs occurring sympatrically at this locality, one of which appeared to be undescribed. Genetic analysis reveals definitively, however, that all three color morphs belong to a single recognized species, Microcebus griseorufus. Indeed, in some cases, the three color morphs can be characterized by identical mitochondrial haplotypes. CONCLUSION: Given these results, we conclude that investigators should always proceed with caution when using a single data source to identify novel species. A synthetic approach that combines morphological, genetic, geographic, and ecological data is most likely to reveal the true nature of species diversity.

Animals↗
PubMed2002

Basic limb kinematics of small therian mammals.

A comparative study of quantitative kinematic data of fore- and hindlimb movements of eight different mammalian species leads to the recognition of basic principles in the locomotion of small therians. The description of kinematics comprises fore- and hindlimb movements as well as sagittal spine movements including displacement patterns of limb segments, their contribution to step length, and joint movements. The comparison of the contributions of different segments to step length clearly shows the proximal parts (scapula, femur) to produce more than half of the propulsive movement of the whole limb at symmetrical gaits. Basically, a three-segmented limb with zigzag configuration of segments is mainly displaced at the scapular pivot or hip joint, both of which have the same vertical distance to the ground. Two segments operate in matched motion during retraction of the limb. While kinematic parameters of forelimbs are independent of speed and gait (with the scapula as the dominant element), fundamental changes occur in hindlimb kinematics with the change from symmetrical to in-phase gaits. Forward motion of the hindlimbs is now mainly due to sagittal lumbar spine movements contributing to half of the step length. Kinematics of small therian mammals are independent of their systematic position, their natural habitat, and also of specific anatomical dispositions (e.g. reduction of fingers, toes, or clavicle). In contrast, the possession of a tail influences 'pelvic movements'.

Animals↗
PubMed2000

Therapeutic strategies in Alzheimer's disease: M1 muscarinic agonists.

The cholinergic hypofunction in Alzheimer's disease (AD) appears to be linked with two other major hallmarks of this disease, beta-amyloid and hyperphosphorylated tau protein. Formation of beta-amyloids might impair the coupling of M1 muscarinic acetylcholine receptors (mAChR) with G-proteins. This can lead to decreased signal transduction, a decrease of trophic and non-amyloidogenic amyloid precursor protein (APPs) and generation of more beta-amyloids, aggravating further the cholinergic deficiency. This review is an attempt to explore the M1 mAChR regulation of beta-amyloid metabolism, tau hyperphosphorylation and cognitive functions. The therapeutic potential of M1-selective muscarinic agonists including AF102B, AF150(S), AF267B (the AF series) is evaluated and compared, when possible, with several FDA-approved acetylcholinesterase inhibitors. These M1 agonists can elevate APPs, decrease tau protein phosphorylation/hyperphosphorylation in vitro and in vivo and restore cognitive impairments in several animal models for AD. Except for the M1 agonists, no other compounds were reported yet with combined effects; e.g., amelioration of cognition dysfunction and beneficial modulation of APPs/beta-amyloid together with tau hyperphosphorylation/phosphorylation. This property of M1 agonists to alter different aspects associated with AD pathogenesis could represent the most remarkable clinical value of such drugs.

Alzheimer Disease↗
PubMed2002

Quantitative assessment of testicular germ cell production and kinematic and morphometric parameters of ejaculated spermatozoa in the grey mouse lemur, Microcebus murinus.

Germ cell production and organization of the testicular epithelium in a prosimian species, the grey mouse lemur, Microcebus murinus, was investigated to extend knowledge of comparative primate spermatogenesis. In addition, semen samples collected from adult male lemurs (body weight 53-92 g; n = 16) by rectal probe electroejaculation were evaluated using computer-assisted morphometric and kinematic analysis of spermatozoa. Epididymidal spermatozoa were collected from six animals after hemicastration; the testes were weighed and prepared for stereological analysis and flow cytometry. The relative testis mass (as a percentage of body weight) ranged between 1.17 and 5.6%. Twelve stages of testicular seminiferous epithelium as described for macaques were applied and only a single stage was observed in most of the seminiferous tubule cross-sections. On average (mean SD), a single testis contained 1870 +/- 829 x 10(6) germ cells and 35 +/- 12 x 10(6) Sertoli cells. Germ cell ratios (preleptotene:type B spermatogonia = 2, round spermatid:pachytene = 3; elongated spermatid:round spermatids = 1) indicated high spermatogenic efficacy. Sperm head dimensions and tail lengths of the ejaculated and epididymidal spermatozoa were similar. Percentages of defects (neck/mid-piece and tail) were low ( 10%) and similar for ejaculated and epididymidal spermatozoa. Spermatozoa were highly motile, characterized by extensive lateral head displacement, but relatively low progressive motility. In conclusion, the grey mouse lemur has unusually large testes with a highly efficient spermatogenic process and large sperm output. These features, together with the high proportion of morphologically normal and highly motile spermatozoa in the ejaculates, indicate that Microcebus murinus is a species in which sperm competition after ejaculation is likely to occur. The predominantly single spermatogenic stage system seems to be an ancestral feature among primates.

Animals↗
PubMed1993

Response to short photoperiod and spontaneous sexual recrudescence in the lesser mouse lemur: role of olfactory bulb removal.

The body weight and sexual activity of the male lesser mouse lemur, a prosimian primate, undergo cyclic changes that are photoperiod-dependent. Exposure to long daylength (LD; 14 h light/day) led to sustained sexual activity, fully developed testes and high plasma testosterone concentrations (228 +/- 25 nmol/l, n = 10). After 14 weeks under LD, a marked decrease in testosterone levels occurred. Gonadal regression was completed within 20 weeks under LD without concomitant changes in body weight. Exposure to short daylength (SD; 8 h light/day) reinforced the sexual quiescence and was associated with a high ponderal gain (from 60 to 110 g). However, independent of the date of gonadal arrest, the sexual activity of males spontaneously resumed at a fixed time after exposure to SD. The testes developed, testosterone concentrations increased to 155 nmol/l and the body weight decreased (from 110 to 80 g) within 20 weeks under SD exposure. The timing for refractoriness appeared very similar under inhibitory and stimulatory photoperiods. This is consistent with the hypothesis that the perception of a critical daylength is used to regulate the timing of the following sexual phase through a mechanism involving photorefractoriness. Contrary to cricetid rodents, a direct response to photoperiodic signals for both body weight and sexual activity were not prevented by olfactory bulb removal in male mouse lemurs. In bulbectomized males (n = 12), sexual activity was stimulated by LD and inhibited by SD. Their plasma testosterone levels, however, significantly differed from those of controls in both photoperiods. Likewise, ponderal cycles remained intact but the fattening phase was delayed and reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of age on glutathione synthesis enzymes in lenses of Old World simians and prosimians.

The activities of gamma-glutamylcysteine synthetase and glutathione synthetase, the two enzymes required for glutathione synthesis, were determined as a function of age in lenses of three species of Old World higher primates: orangutan, pigtail monkey and olive baboon. These were compared to enzyme activities in lenses of two prosimians: mouse lemur and galago. gamma-Glutamylcysteine synthetase activity decreased as a function of age in all three Old World simians. The rate of decrease was greatest in the juvenile lenses. In contrast, the enzyme activity increased continuously with age in the galago lens. In the mouse lemur the enzyme activity increased per lens, but was constant when expressed as specific activity or as units per gram of lens. The loss of enzyme activity with age was limited to Old World higher primates apparently representing genetic change. Glutathione synthetase activity decreased logarithmically with age in the lenses of all five species.

Aging↗
PubMed2002

Shoulder movements during quadrupedal locomotion in arboreal primates.

The kinematics of scapula and shoulder joint movements were analyzed in three species of arboreal quadrupedal primates using cineradiography. Our findings indicate that scapular movement is highly important for forelimb movement in primates with this ancestral mode of locomotion. Retroversion of the scapula (syn. caudal rotation or extension) during the stance phase contributes more than 40% to the stride length of the forelimb. Lateral forelimb excursions, a general feature for arboreal primates, are based on complex three-dimensional scapular movements guided by the clavicle. Humeral abduction is achieved by scapular abduction and transversal rotation of the scapula about its longitudinal axis, and is therefore strikingly different from humeral abduction in humans. At the same time, the movements of the shoulder joint are limited to flexion and extension only.

Animals↗
PubMed1992

Systematisation of the olfactory bulb efferent projections in a lemurian primate: Microcebus murinus.

In order to investigate a sensorial pathway essential in animal behavior, the efferent projections of the olfactory bulbs in Microcebus murinus were identified after transection of one olfactory peduncle and revelation of degenerating fibers by various silver staining methods. Total and partial sections have enabled the demonstration of the involvement in the olfactory projection areas of each olfactory tract: the lateral olfactory tract (LOT) and the intermediate olfactory tract (IOT), either via the medial forebrain bundle (MFB) or not. The IOT fibers innervate the cortex, the anterior olfactory nucleus, the caudate-putamen, the septum and the hippocampus on both sides. The LOT fibers reach the olfactory tubercle, the piriform cortex, the entorhinal cortex and the amygdala on both sides. Olfactory fibers could also be observed in the MFB innervating on both sides firstly the hypothalamic areas (the lateral hypothalamus, the suprachiasmatic, posterior supraoptic, mammillary nuclei and the median eminence), and then the mesencephalic structures (the locus coeruleus and the raphe nuclei). It may be concluded that the olfactory bulbs are not only connected with above-mentioned telencephalic areas, but are also directly related to the vegetative and integrative brain areas located in the hypothalamus and the brainstem and especially with the major nuclei which play an essential role in neurovegetative, neuroendocrine and behavioral regulation.

Animals↗
PubMed2005

Parasite burden and constitution of major histocompatibility complex in the Malagasy mouse lemur, Microcebus murinus.

We investigated the importance of the major histocompatibility complex (MHC) constitution on the parasite burden of free-ranging mouse lemurs (Microcebus murinus) in four littoral forest fragments in southeastern Madagascar. Fourteen different MHC class II DRB-exon 2 alleles were found in 228 individuals with high levels of sequence divergence between alleles. More nonsynonymous than synonymous substitutions in the functional important antigen recognition and binding sites indicated selection processes maintaining MHC polymorphism. Animals from the four forest fragments differed in their infection status (being infected or not), in the number of different nematode morphotypes per individual (NNI) as well as in the fecal egg counts (FEC) values. Heterozygosity in general was uncorrelated with any of these measures of infection. However, a positive relationship was found between specific alleles and parasite load. Whereas the common allele Mimu-DRB*1 was more frequently found in infected individuals and in individuals with high NNI and FEC values (high parasite load), the rare alleles Mimu-DRB*6 and 10 were more prevalent in uninfected individuals and in individuals with low NNI and FEC values (low parasite load). These three alleles associated with parasite load had unique amino acid motifs in the antigen binding sites. This distinguished them from the remaining 11 Mimu-DRB alleles. Our results support the hypothesis that MHC polymorphism in M. murinus is maintained through pathogen-driven selection acting by frequency-dependent selection. This is the first study of the association of MHC variation and parasite burden in a free-ranging primate.

Analysis of Variance↗
PubMed1995

Immunocytochemical characterization of Tau proteins during cerebral aging of the lemurian primate Microcebus murinus.

The immunocytochemistry of Tau proteins in the cortical pyramidal neurons of the adult microcebes has been studied, using antibodies against human normal and pathological Tau proteins. Some changes related to the age and to some pathologies were observed. In fact, during the adult life, Tau proteins appeared as very thin granulations scattered in the whole neuronal cytoplasm. With age, a part of these proteins aggregated and became like thick granules at the neuron periphery; the distribution was not uniform, and numerous neurons with aggregated Tau proteins were observed in amyloid plaque-containing brains. Abnormally phosphorylated Tau proteins were also observed in some aged animals, using an absorbed anti-PHF recognizing the pathological Tau proteins characteristic of Alzheimer's disease. This present work confirms that the microcebe is a good model for studying disfunctions involved in the normal cerebral aging and in some neurodegenerative disorders which affect humans.

Adult↗
PubMed1995

Immunocytochemical characterization of Tau proteins during cerebral aging of the lemurian primate Microcebus murinus.

The immunocytochemistry of Tau proteins in the cortical pyramidal neurons of the adult microcebes has been studied, using antibodies against human normal and pathological Tau proteins. Some changes related to the age and to some pathologies were observed. In fact, during the adult life, Tau proteins appeared as very thin granulations scattered in the whole neuronal cytoplasm. With age, a part of these proteins aggregated and became like thick granules at the neuron periphery; the distribution was not uniform, and numerous neurons with aggregated Tau proteins were observed in amyloid plaque-containing brains. Abnormally phosphorylated Tau proteins were also observed in some aged animals, using an absorbed anti-PHF recognizing the pathological Tau proteins characteristic of Alzheimer's disease. This present work confirms that the microcebe is a good model for studying disfunctions involved in the normal cerebral aging and in some neurodegenerative disorders which affect humans.

Amyloid beta-Peptides↗
PubMed1995

Biochemical characterization of Tau proteins during cerebral aging of the lemurian primate Microcebus murinus.

Tau proteins extracted from the brain of 12 adult microcebes ranging from 2 to 9 years old were characterized by Western blots, using immunological probes against normal and pathological human Tau proteins. In microcebes, the molecular weight of Tau proteins increases during aging, with variants of 52-54, 64, 67 kDa in the young adult and variants of 60 and 70 kDa in the oldest animal studied. The increase of the apparent molecular weight is due to a change of conformation and a stabilization in the "hyperphosphorylated" state, as revealed with phosphorylation-dependent monoclonal antibodies Tau-1 and AD2. Furthermore, AD1 specifically detected Alzheimer-type epitopes on the 60 kDa Tau isoform from a very old microcebe. These results suggest that Microcebus murinus is an interesting model for the study of the biochemical dysfunctions that occur in the human brain during aging and Alzheimer disease.

Aging↗
PubMed1993

[Similarities between cerebral amyloid plaques in aged lemurian and in human with Alzheimer's disease].

Microcebus cerebral cortex has been investigated using various technics: amyloid beta-A4 protein, alpha-1 antichymotrypsin and ubiquitin immunocytochemistry, thioflavin S staining for amyloid deposition and Bodian's silver impregnation not only for amyloid plaques but also for degenerated neurites; glial fibrillary acidic protein (GFAP) immunocytochemistry has been also used for astrocytes. Parenchymal beta-A4 amyloid is observed to be deposited in some aged Microcebus cerebral cortex in three forms: 1) diffuse plaques of about 100 microns in diameter; 2) dense plaques with compact amyloid core which are thioflavin-positive; these two types of amyloid plaques (AP) are also stained both with the antibodies against alpha 1-antichymotrypsin and ubiquitin respectively; they are also associated with GFAP-immunoreactive astrocytes; 3) extensive ribbon-like infiltrations enclosing multiple blood vessels. The distribution of the AP using an automatic image analyser has showed that the density of the AP in the neocortex fluctuates among the different cortical regions. The density is respectively up to 16 AP/mm2 in the superior part of the temporal lobe and 12 AP/mm2 in the amygdala, 9 AP/mm2 in the prefrontal area of the frontal lobe and 11 AP/mm2 in the central area, 10 AP/mm2 in the parietal lobe and 5 AP/mm2 in the occipital lobe. The compact AP are more often observed in the temporal lobe. In Alzheimer's disease the AP are also made of amyloid beta-A4 protein, alpha 1-antichymotrypsin and ubiquitin. As in Microcebus, in Alzheimer's disease two types of AP are observed: the diffuse and the compact AP; the latter are also thioflavin S positive. The dense AP are not so numerous as the diffuse AP and the density of the AP is greater in the temporal lobe. All these results lead to the conclusion that the AP occurred in age Microcebus brain are similar in many respects to those found in Alzheimer's disease. So, Microcebus murinus, lemurian primate of small size (about 100 g) and relatively short life span (up to 12 years), should provide a valid animal model for investigation of some principal features of Alzheimer's disease.

Alzheimer Disease↗