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PubMed1985

Age-related changes in the subiculum of Macaca mulatta: synaptic density.

Dendritic spines and synapses were quantitated in the subiculum of 12 Macaca mulatta from 7 to 29 years of age. Dendritic spines were analyzed in six dendritic foci of pyramidal neurons impregnated by the Golgi-Cox method. The dendritic foci examined were the apical shaft, apical oblique, apical tuft, apical terminal, basal terminal, and basal dendrites. Electron microscopic observations were made on synapses stained with ethanolic phosphotungstic acid. There was no difference in spine density between a group of young (7 to 12 years of age) and middle-aged (18 to 21 years) animals. The mean spine density was 1.09/microns for the young and 1.15/microns for the middle-aged animals. In contrast, the spine density of the old animals was 0.87/microns, which was significantly lower than the spine density found in the young and middle-aged animals. A loss of dendritic spines in the old animals occurred equally in all six dendritic foci. A decline in synaptic density in the aged animals were further evidenced by an ultrastructural analysis. The synaptic density of the old animals was 8.3 X 10(8)/mm3, significantly lower than 9.5 X 10(8)/mm3 and 10.2 X 10(8)/mm3 found in the young and middle-aged animals, respectively. This study on synaptic density demonstrated the decline in synaptic number as a function of age in M. mulatta.

Aging↗
PubMed1985

Age-related changes in the subiculum of Macaca mulatta: dendritic branching pattern.

The dendritic branching pattern was studied in the subiculum of nine Macaca mulatta from 7 to 28 years of age. Morphometric analysis of pyramidal neurons revealed significant age-related differences at various designated branch orders in both the centrifugal and centripetal ordering methods. There was continued branching and growth of the apical dendrites in adulthood. Basal dendrites did not show any added complexity, but rather showed continued growth of existing terminal branches. The three oldest animals showed a preferential loss of whole terminal branches on the apical portion of the dendritic tree, whereas shortening of existing terminal branches was the characteristic feature of the basal dendrites. Data obtained from the subiculum provide quantitative evidence indicating the considerable potential for dendritic plasticity beyond the early developmental stages and eventual loss of dendritic complexity in the old M. mulatta.

Aging↗
PubMed1986

Regulation of bilirubin glucuronide synthesis in primate (Macaca fascicularis) liver. Kinetic analysis of microsomal bilirubin uridine diphosphate glucuronyltransferase.

Hepatic bilirubin uridine diphosphate glucuronyl-transferase (UDP-glucuronyltransferase) catalyzes the formation of bilirubin monoglucuronides (BMG, C-8 and C-12 isomers) and bilirubin diglucuronide (BDG) from bilirubin and the cosubstrate, UDP-glucuronic acid. Distinctive patterns of bile pigment excretion occur in different species and in pathologic disorders (e.g., Gilbert's syndrome). In normal human and monkey (Macaca fascicularis) bile, the proportion of BDG exceeds that of BMG and the C-8/C-12 BMG isomer ratio approaches unity. To investigate the mechanisms responsible for the patterns of BDG and BMG isomers in bile, we used a radiochemical assay to analyze the kinetics and regulation of bilirubin UDP-glucuronyltransferase in microsomes prepared from monkey liver. The synthesis of BMG from bilirubin was a higher capacity, lower affinity step (Vmax = 295 pmol/mg protein X min, Km = 24 microM) than BDG synthesis from endogenously formed BMG (Vmax = 170 pmol/mg protein X min, Km = 14 microM). This observation was confirmed when biosynthetically prepared BMG was used as substrate. The rate of formation of BDG relative to BMG was modulated by both bilirubin and UDP-glucuronic acid concentration, whereas the C-8/C-12 BMG isomer ratio was influenced exclusively by UDP-glucuronic acid concentration. The data obtained with increasing UDP-glucuronic acid concentration did not obey conventional single-site kinetics, suggesting the presence of more than one binding site on the enzyme or a membrane transporter for this nucleotide sugar. These findings demonstrate that microsomal bilirubin UDP-glucuronyltransferase has a greater capacity for BMG than BDG synthesis, and thus support the concept that the decreased BDG/BMG ratio in the bile of patients with reduced hepatic enzyme activity (i.e., Gilbert's syndrome and type II Crigler-Najjar disease) reflects the diminished capacity of the enzyme to synthesize BDG from BMG. Bilirubin and UDP-glucuronic acid concentrations both appear to be pivotal in regulating the synthesis of individual bilirubin glucuronides and hence the patterns of bilirubin conjugates excreted in bile.

Animals↗
PubMed1980

Dose-response relationship for x-ray-induced reciprocal translocations in stem-cell spermatogonia of the rhesus monkey (Macaca mulatta).

The induction of reciprocal translocations in stem-cell spermatogonia of the rhesus monkey (Macaca mulatta) was studied after testicular X-irradiation of mature males (50, 100 and 200 rad) or whole-body irradiation of young males (200 and 300 rad). After the recovery of the germinal epithelium, cytogenetic analysis was carried out on spermatocytes descended from irradiated spermatogonia. Preparations of C-banded diakinesis-metaphase I were screened for translocation configurations. The frequencies of aberrations obtained were 0% at 0 rad, 0.36% at 50 rad, 0.86% at 100 rad, 0.99% at 200 rad and 0.68% at 300 rad, suggesting a humped dose-response relationship. There was no evidence for the contribution of a quadratic component to the yield in the lower dose range. A comparison of these results with those obtained for other mammals by a number of investigators shows that the frequencies of translocations in the rhesus monkey are much lower than those published for most other mammalian species.

Animals↗
PubMed1984

Diagrammatic representation for chromosomal mutagenesis studies. II. Radiation-induced rearrangements in Macaca fascicularis.

A qualitative study is presented of chromosomal rearrangements induced in peripheral blood lymphocytes of Macaca fascicularis, after exposure to gamma-irradiation at 2 Gy and 3 Gy. The use of a new diagrammatic representation allowed us to compare, for each type of rearrangement, the distribution of the observed break-points with the theoretical random distribution. It was concluded that chromosomal mutagenesis does not occur at random: an excess of involvement of small chromosomes is found for dicentrics and reciprocal translocations; an excess of telomeric breaks exists in dicentrics and paracentric inversions. In our sample of 27 pericentric inversions, the larger chromosomes are too frequently involved, 2 different inversions are observed at least twice and 7 (or 8) reproduce chromosomes of other primates.

Animals↗
PubMed1985

Dose-response relationship of gamma-ray-induced reciprocal translocations at low doses in spermatogonia of the crab-eating monkey (Macaca fascicularis).

The yield of translocations induced by acute gamma-irradiation at low doses (0.25 and 0.50 Gy) in the crab-eating monkey's (Macaca fascicularis) spermatogonia was examined. The frequencies of translocations per cell were 0.53% at 0.25 Gy and 1.07% at 0.50 Gy. Over the low dose range from 0 to 1 Gy, the dose-response relationship for translocation yield was a linear one with a regression coefficient of 1.79 X 10(-2). To estimate the sensitivity to the induction of translocations in the crab-eating monkey's spermatogonia, the slope of the regression line was compared with those in other mammalian species. Consequently, over the low dose range below 1 Gy, the sensitivity of the crab-eating monkey's spermatogonia to translocation induction was similar to several mammalian species, the mouse. Chinese hamster, and the rabbit, but significantly higher than that of the rhesus monkey and lower than that of the marmoset.

Animals↗
PubMed1984

Effects of social factors on adrenal weight and related physiology of Macaca fascicularis.

Increased adrenal cortical activity and hypertrophy of adrenal glands associated with defeat and social subordination have been reported frequently in small mammals; these adrenal changes have been linked to impairments in immune response, glucose metabolism and reproductive performance. Similar studies in primates have produced variable results. The current study was undertaken to illuminate the effects of social status on the adrenal gland and to examine concurrent effects of social variables on other physiological systems in Macaca fascicularis, in an initial exploration of the hypothesis that high and low social status have different physiological consequences. Sixty adult male M. fascicularis were housed in social groups of n = 5, under either stable or unstable social conditions. It was found that subordinate animals had heavier adrenal glands and somewhat higher plasma glucose concentrations than dominants. In contrast, dominants had higher blood pressure and worsened atherosclerosis, under some conditions, than subordinates. These data appear to offer preliminary support for Henry and Stephen's hypothesis of differential arousal of dominant and subordinate animals.

Adrenal Glands↗
PubMed1985

Techniques for improving stereotaxic accuracy in Macaca fascicularis.

Sources of stereotaxic variability in long-tailed macaques (Macaca fascicularis) were examined by X-ray techniques. Accuracy in the vertical dimension can be improved significantly by measuring from the top of the brain rather than from the Frankfurt plane established by external bony landmarks. Even greater accuracy in both the vertical and anterior-posterior dimensions can be attained by rotating the cranium in the stereotaxic instrument to bring the intercommissural line, as defined by ventriculography, into a plane parallel to the horizontal stereotaxic plane, thus approximating the orientation of the brain as represented in both of the brain atlases currently available for this species. An adjustable eyebar spacer, which allows the cranium to be rotated in the stereotaxic instrument, is described.

Animals↗
PubMed1985

X-ray localization of limbic structures in the cynomolgus monkey (Macaca fascicularis).

The anterior/posterior (AP) and dorsal/ventral positions of 3 subcortical structures, the amygdala, the mamillary bodies, and the anterior commissure, were estimated with respect to the skull in a series of cynomolgus monkeys (Macaca fascicularis). The distance from the external auditory meatus, from which stereotaxic coordinates are typically derived, to these structures was found to be highly variable. In contrast, radiography revealed that a skull landmark which forms part of the sphenoid bone lies at a remarkably constant distance from these 3 structures. The posterior clinoid process also proved to be a more accurate reference point than the auditory meatus, although it was less reliable than the sphenoid landmark. It is proposed that the position of the sphenoid bone could be used to localize a wide range of limbic and basal forebrain structures.

Amygdala↗
PubMed1979

Rhesus monkey (Macaca mulatta) model in genetic toxicology mitomycin C clastogenicity in germ cells.

The value of rhesus monkeys (Macaca mulatta) as a genetic toxicology model is limited by their scarcity, expense, and impracticality of progeny testing. However, in some special circumstances, e.g., accidental exposure of humans to potential mutagens, rhesus monkeys or other primates may provide a superior animal model to help to cope with a difficult public health situation. Using the testis as a target organ we found that when primary spermatocytes were treated in pre-leptotene stage with 1 mg mitomycin C/kg body weight, the frequency of exchanges, fragments, sex-chromosome and autosomal univalents increased significantly at diakinesis-metaphase I. This response was absent in cells treated during diplotene, late pachytene or during spermatogonial stages. We suggested that animals should be evaluated not only for genetic toxicology parameters, but also toxicologically, histologically, behaviorally, for carcinogenesis and seminal cytology. Whenever possible, the animals should be recycled.

Animals↗
PubMed1989

Origins of the renal innervation in the primate, Macaca fascicularis.

The origins of the renal efferent and afferent nerves in 5 cynomolgus monkeys (Macaca fascicularis) were studied by using the retrograde transport of horseradish peroxidase (HRP) and horseradish peroxidase-wheat germ agglutinin (HRP-WGA). The cut ends of the right renal nerves were soaked for 30-45 min in solutions consisting of 15% HRP and 1% HRP-WGA. Three or four days later the animals were killed and the tissues examined for the presence of retrogradely labeled neurons, HRP-filled cells were observed, with rare exceptions, only in ganglia ipsilateral to the side of tracer application. Renal efferent neurons (4648-14565 cells per animal) were found in relatively equal numbers in prevertebral and paravertebral (sympathetic chain) ganglia. Labeled prevertebral cells were distributed among the renal (52%), aorticorenal (32%) and superior mesenteric (16%) ganglia, whereas labeled paravertebral neurons were mainly located in chain ganglia T11-L3, with 94% of these located in L1-3. Labeled renal sensory neurons (31-543 per animal) constituted less than 5% of all labeled cells and were found in ipsilateral dorsal root ganglia T10-L3, with (80%) in T12 and L1. The labeled sensory neurons ranged from 18-64 microns in diameter (X = 32.4 microns). With the exception of a single cell in one animal, no labeled neurons were observed in the nodose ganglia. Many parallels were observed between the organization of the renal plexuses of macaques and humans, suggesting the utility of the non-human primate as an experimental model for functional studies of renal innervation in humans.

Animals↗
PubMed1987

The inheritance of a Macaca fascicularis red cell antigen detected by CAMPATH-1 antibody.

CAMPATH-1 monoclonal antibody is reactive with human lymphocytes and monocytes and it has been shown to bind to antigens on the red cells of a number of primate species, including Macaca fascicularis. Our study within a closed colony of breeding M. fascicularis monkeys has confirmed this finding, and shown that the antibody identified a single red cell antigen inherited in Mendelian fashion as a dominant character. We have, further, confirmed that the antigen is present on blood lymphocytes, even in animals whose red cells are negative. This CAMPATH-1 antigen can therefore serve as a useful red cell marker in experiments involving bone marrow transplantation or blood transfusion.

Animals↗
PubMed1988

Ultrastructural evidence for direct monosynaptic rubrospinal connections to motoneurons in Macaca mulatta.

The magnocellularis division of the red nucleus of the Macaca mulatta, a midbrain structure involved in processing motor information, is known by light microscopic analysis to project, via the rubrospinal tract, to the contralateral intermediate horn of the spinal cord. Physiological studies, however, provide additional evidence for direct monosynaptic connections to motoneurons subserving distal musculature. This electron microscopic study demonstrates, by analyzing the anterograde transport of 5% wheatgerm agglutinin-horseradish peroxidase injected into the red nucleus, the presence of labeled terminals synapsing upon somata and proximal dendrites of motoneurons in the lateral portion of the ventral horn of the cervical enlargement of the spinal cord. We conclude that this anatomical evidence confirms the presence of direct monosynaptic connections to spinal motoneurons in the primate.

Animals↗
PubMed1982

Pteridine-metabolizing enzymes of Macaca fascicularis.

1. The crab-eating monkey (Macaca fascicularis) has been studied for enzymes which react in the biosynthesis of pteridine cofactor of phenylalanine hydroxylase: 2. Rather high activity of sepiapterin reductase (EC 1.1.1.153)(0.130 mumol) and measurable activity of dihydrofolate reductase (EC 1.5.1.3)(0.039 mumol), (in amount of substrate reduced/hr/mg protein at 37 degrees C) were found in the crude extract from the liver. 3. Sepiapterin reductase was observed, in blood, only in the erythrocytes while dihydrofolate reductase was observed both in erythrocytes and leucocytes. 4. Activity of pteridine cofactor of phenylalanine hydroxylase was detected in the extract of the liver. 5. Sepiapterin reductase was partially purified from the liver, and was studied in the mol. wt, coenzyme-requirement, pH optimum, KmS and inhibitors.

Alcohol Oxidoreductases↗
PubMed2006

Comparative phylogenetics offer new insights into the biogeographic history of Macaca fascicularis and the origin of the Mauritian macaques.

We employ a comparative phylogenetic analysis to gain insight into the recent evolutionary history of Macaca fascicularis, the long-tailed macaque. Mitochondrial and Y-chromosomal topologies both show that, in general, the deepest intraspecific bifurcations separate Indochinese and Sundaic forms of this species. Sumatran populations, however, are an exception: they carry one Y-chromosomal lineage that clusters with continental populations, and another that clusters with insular stocks. This discovery provides insight into two events in the history of M. fascicularis. First, the presence of the 'continental' Y-lineage on Sumatra is one of the strongest lines of evidence to date for recent (Late Pleistocene) gene flow between Indochinese and Sundaic populations. Second, since Sumatra is the only region known to carry 'continental' YDNA and 'insular' mtDNA, it is considered the most likely source of the Mauritian macaques-an important biomedical research stock that appears to carry this mtDNA/YDNA combination exclusively.

Animals↗
PubMed1979

Testicular steroidogenesis in the rhesus monkey (Macaca mulatta.

Studies were undertaken to investigate testicular steroidogenesis in the Rhesus monkey Macaca mulatta. Testicular fragments (50 mg) were incubated for 3 hr with pregnenolone-7-3H or with progesterone-7-3H. The major metabolite of pregnenolone was progesterone (70.1%), with a lesser conversion to 17-hydroxyprogesterone (1.6%), androstenedione (3.3%), and testosterone (7.2%). The delta-5 intermediates 17-hydroxypregnenolone (4.6%) and dehydroepiandrosterone (8.6%) were also identified in the pregnenolone incubates. A majority of the progesterone substrate was not metabolized by the testicular fragments (80.1%), while some conversion to 17-hydroxyprogesterone (3.4%), androstenedione (4.8%), and testosterone (11.7%) occurred in the incubates. These results suggest that testicular fragments from the Rhesus monkey may convert pregnenolone to testosterone through both the delta-4 and the delta-5 pathways.

Androstenedione↗
PubMed1981

[Observation of a photosensitive syndrome in Macaca nemestrina (author's transl)].

Out of a group of 12 M. nemestrina (originating from Malaysia), 9 adults had shown clinical signs induced by ILS at 25 c/sec. Six of them (3 males, 3 females) were very photosensitive; however, only 2 presented eyelid and/or head jerks after the end of ILS (level 4), but never a generalized seizure. Tactile periorbital stimuli favoured myoclonus. In all but the two of level 4, the intensity of clinical signs varied from one day to the next. In all implanted adult macaques, spontaneous paroxysmal EEG activities were seen during slow sleep in mostly anterior areas, but also during waking and REM sleep in some of them; however, their occurrence depended upon the individual and were not in all cases related to their level of photosensitivity. During ILS, paroxysmal discharges (spikes and waves and/or polyspikes and waves), isolated or in bursts at 3-4/sec were bilateral and symmetrical. They started in fronto-rolandic regions, then became generalized. This observation constitutes a new fact since the discovery, in 1966, of the photomyoclonic syndrome of Papio papio, Macaca nemestrina being another species of subhuman primates with a marked predisposition to photosensitive epilepsy.

Aging↗
PubMed1987

Homologues of the human C and A apolipoproteins in the Macaca fascicularis (cynomolgus) monkey.

We used antisera to human A and C apolipoproteins to identify homologues of these proteins among the high-density lipoprotein apoproteins of Macaca fascicularis (cynomolgus) monkeys, and NH2-terminal analysis was used to verify the homology. The NH2-terminal sequence of the M. fascicularis apoA-I is identical with that of another Old World species, Erythrocebus patas, and differs from human apoA-I at only 4 of the first 24 residues. M. fascicularis apoA-II contains a serine for cysteine replacement at position 6 and is therefore monomeric like the apoA-II from all species below apes. Human and monkey apoA-II are not otherwise different through their first 25 residues. About 20% of M. fascicularis apoC-I aligns with human apoC-I through residue 22, and 80% lacks an NH2-terminal dipeptide. Otherwise, the monkey apoC-I differs from the human protein at only 2 of 25 positions. Two forms of M. fascicularis apoC-II were identified. ApoC-II1 is highly homologous with human apoC-II, whereas an NH2-terminal hexapeptide is absent from apoC-II2. ApoC-II2 was the predominant species, and apoC-II1 appears to represent a propeptide from which a hexapeptide prosegment is cleaved at a Gln-Asp bond. Both forms of monkey apoC-II are potent activators of lipoprotein lipase. There are two polymorphic forms of M. fascicularis apoC-III, and their electrophoretic mobilities become identical after treatment with neuraminidase. Except for a glycine for serine substitution at position 10, the first 15 NH2-terminal residues of M. fascicularis and human apoC-III are the same.

Amino Acid Sequence↗