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At least 865 records · Page 48Linked to original sources
PubMed2001

Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism in man and non-human primates. Monoamine-oxidase B (MAO-B) has been reported to be implicated in both MPTP-induced parkinsonism and Parkinson's disease, since selegiline (L-deprenyl), an irreversible MAO-B inhibitor, prevents MPTP-induced neurotoxicity in numerous species including mice, goldfish and drosophyla. However, one disadvantage of this substance relates to its metabolism to (-)-methamphetamine and (-)-amphetamine. Rasagiline (R-(+)-N-propyl-1-aminoindane) is a novel irrevesible MAO-B-inhibitor, which is not metabolized to metamphetamine and/or amphetamine. The present study compared the effects of high doses of selegiline and rasagiline (10 mg/kg body weight s.c.) on MPTP-induced dopaminergic neurotoxicity in a non-human primate (Callithrix jacchus) model of PD. Groups of four monkeys were assigned to the following six experimental groups: Group I: Saline, Group II: Selegiline/Saline, Group III: Rasagiline/Saline, Group IV: MPTP/Saline, Group V: Rasagiline/MPTP, Group VI: Selegiline/MPTP. Daily treatment with MAO-B-inhibitors (either rasagiline or selegiline, 10 mg/kg body weight s.c.) was initiated four days prior to MPTP-exposure (MPTP-HCl, 2 mg/kg body weight subcutaneously, separated by an interval of 24 hours for a total of four days) and was continued until the end of the experiment, i.e. 7 days after the cessation of the MPTP-injections, when animals were sacrificed. MPTP-treatment caused distinct behavioural, histological, and biochemical alterations: 1. significant reduction of motor activity assessed by clinical rating and by computerized locomotor activity measurements; 2. substantial loss (approx. 40%) of dopaminergic (tyrosine-hydroxylase-positive) cells in the substantia nigra, pars compacta; and 3. putaminal dopamine depletion of 98% and its metabolites DOPAC (88%) and HVA (96%). Treatment with either rasagiline or selegiline markedly attenuated the neurotoxic effects of MPTP at the behavioural, histological, and at the biochemical levels. There were no significant differences between rasagiline/MPTP and selegiline/MPTP-treated animals in respect to signs of motor impairment, the number of dopaminergic cells in the substantia nigra, and striatal dopamine levels. As expected, both inhibitors decreased the metabolism of dopamine, leading to reduced levels of HVA and DOPAC (by >95% and 45% respectively). In conclusion, rasagiline and selegiline at the dosages employed equally protect against MPTP-toxicity in the common marmoset, suggesting that selegiline-derived metabolites are not important for the neuroprotective effects of high dose selegiline in the non-human MPTP-primate model in the experimental design employed. However, unexpectedly, high dose treatment with both MAO-inhibitors caused a decrease of the cell sizes of nigral tyrosine hydroxylase positive neurons. It remains to be determined, if this histological observation represents potential adverse effects of high dose treatment with monoamine oxidase inhibitors.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2004

Biochemical bone turnover markers are useful tools to assess changes in bone metabolism in marmosets.

This study was designed to investigate whether biochemical markers of bone resorption and formation could be determined in the serum and urine of marmosets (Callithrix jacchus), using standard laboratory chemistry methods and commercially available human kits. Consequently, the findings from this study will indicate whether the techniques and kits could serve as appropriate tools for assessing changes in bone turnover in this species. Two groups of animals (n = 12/group), consisting of a comparable number of young and old male and female marmosets, were given either isotonic saline or a single dose of the bisphosphonate ibandronate (0.1 mg/kg) s.c. in order to suppress bone turnover. Blood and urine were collected at baseline and 5 days after administration. Samples were analyzed for urinary (u) and serum (s) markers of bone formation (serum osteocalcin [sOC], serum N-terminal crosslinks of human pro-collagen type I [sP1NP]) and bone resorption (urinary pyridinoline [uPYD], urinary deoxypyridinoline [uDPD], serum C-terminal crosslinks of human collagen type I (C-telopeptide) [sCTX]), intact serum parathyroid hormone (iPTH) and urinary calcium and creatinine. Levels of all the markers of bone resorption and formation decreased during the study period. As expected, the bone formation markers decreased slightly less relative to the resorption markers. The most sensitive markers were sCTX (-33%; P < or =0.001) for bone resorption, and sP1NP (-3%; P < or =0.05) for bone formation. Serum PTH levels increased by 8% ( P < or =0.05), demonstrating a physiological reaction to prevent changes in serum calcium. Although not all variables reached statistical significance within the tested interval, the applied methods and kits were considered suitable for evaluating bone turnover changes in marmosets. Thus, these methods and kits can be utilized not only during the course of pharmacological investigations but also as additional tools to assess the overall bone health of this species.

Animals↗
PubMed2006

A new mark test for mirror self-recognition in non-human primates.

For 30 years Gallup's (Science 167:86-87, 1970) mark test, which consists of confronting a mirror-experienced test animal with its own previously altered mirror image, usually a color mark on forehead, eyebrow or ear, has delivered valuable results about the distribution of visual self-recognition in non-human primates. Chimpanzees, bonobos, orangutans and, less frequently, gorillas can learn to correctly understand the reflection of their body in a mirror. However, the standard version of the mark test is good only for positively proving the existence of self-recognition. Conclusive statements about the lack of self-recognition are more difficult because of the methodological constraints of the test. This situation has led to a persistent controversy about the power of Gallup's original technique. We devised a new variant of the test which permits more unequivocal decisions about both the presence and absence of self-recognition. This new procedure was tested with marmoset monkeys (Callithrix jacchus), following extensive training with mirror-related tasks to facilitate performance in the standard mark test. The results show that a slightly altered mark test with a new marking substance (chocolate cream) can help to reliably discriminate between true negative results, indicating a real lack of ability to recognize oneself in a mirror, from false negative results that are due to methodological particularities of the standard test. Finally, an evolutionary hypothesis is put forward as to why many primates can use a mirror instrumentally - i.e. know how to use it for grasping at hidden objects - while failing in the decisive mark test.

Animals↗
PubMed1992

Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey.

Programmed electrical stimulation was used to examine the ability of long-term dietary lipid modulation to influence myocardial vulnerability to the induction of ventricular fibrillation in adult marmoset monkeys (Callithrix jacchus). Marmosets fed diets supplemented (to a total of 28.5% of the energy as fat) with polyunsaturated fatty acid (PUFA)-rich tuna fish oil or sunflower seed oil had significantly elevated mean ventricular fibrillation threshold compared with those fed a saturated animal fat supplemented diet or a reference diet not supplemented with fat (11.2% of the energy as fat). Fibrillation threshold was reduced during acute myocardial ischemia induced by coronary artery occlusion but still remained higher in the PUFA-fed animals than either the control or the ischemic threshold in reference or saturated fat supplemented animals. Dietary tuna fish oil was associated with a low incidence of sustained fibrillation episodes and no fatalities. These results indicate that myocardial substrate vulnerability to arrhythmic stimuli is increased during ischemia in a nonhuman primate model but dietary PUFA can reduce vulnerability under both normal and ischemic conditions. Reduced dietary fat intake alone was without effect.

Animals↗
PubMed1981

Demonstration of ocular dominance columns in a New World primate by means of monocular deprivation.

We investigated the pattern transneuronally transported [3H]proline to the visual cortex of normal and deprived marmosets (Callithrix jacchus). In the normal marmoset a continuous band of label was evident within layer IV of striate cortex. Following injection of the closed eye of deprived marmosets, distinct fluctuations of label were apparent over the base of layer IV in both hemispheres. These results support the hypothesis that the presence of ocular separation of geniculo-striate afferents is a feature common to all primates.

Animals↗
PubMed1996

Dopamine D3 receptors in the basal ganglia of the common marmoset and following MPTP and L-DOPA treatment.

The distribution of the dopamine D3 receptor was studied by receptor autoradiography using [3H]7-OH-DPAT in striatal and extrastriatal brain regions of the common marmoset (Callithrix jacchus). Saturation studies demonstrated that [3H]7-OH-DPAT bound with similar affinity to different regions of marmoset brain. In normal marmosets, specific [3H]7-OH-DPAT binding was found in both striatal and extrastriatal regions. Very high levels of specific [3H]7-OH-DPAT binding were detected in the islands of Calleja and nucleus accumbens but in addition high levels of binding were detected in rostral caudate nucleus and putamen. In common marmosets treated with the selective nigral neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the levels of specific [3H]7-OH-DPAT binding in striatal and extrastriatal regions were not different to those in normal animals. Chronic treatment of MPTP-treated marmosets with L-DOPA/ carbidopa did not alter the levels of specific [3H]7-OH-DPAT binding in any brain region. These results demonstrate that in common marmosets D3 receptors are located in both striatal and limbic regions. The receptor density is not altered by dopaminergic denervation or by chronic L-DOPA administration. The D3 receptor may, therefore, be important in both the therapeutic and adverse effects of drugs used to treat Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Binding of human lymphocyte-specific monoclonal antibodies to common marmoset lymphoid cells.

Commercially available monoclonal antibodies which bind to human lymphocyte subsets were screened for their ability to bind to lymphoid cells from the common marmoset Callithrix jacchus. Anti-Leu-5 and T11 were the only pan T-cell antibodies which reacted strongly. None of the antibodies which bind human lymphocytes of the helper/inducer subpopulation reacted with C. jacchus cells and only one antibody, T8, specific for the cytotoxic/suppressor subset, bound to the marmoset cells. The two antibodies tested which bind human B cells, B1 and anti-HLA-DR, were also reactive with marmoset cells. The cellular specificity of the T11, T8, and B1 antibodies was determined by dual binding studies on the fluorescence-activated cell sorter. The B1 antibody bound only Ig+ cells and all Ig+ cells were B1+. The T11 and T8 antibodies bound only to Ig- marmoset lymphoid cells and, as in the human, all T8+ marmoset cells were also T11+. Thus, using these monoclonal antibodies in the common marmoset one can identify three populations of lymphoid cells: (1) T11+, T8+ cells; (2) T11+, T8- cells; (3) B1+ cells.

Animals↗
PubMed1984

The myoglobin of primates: the Night Monkey, Aotes trivirgatus (Cebidae, Platyrrhini, Anthropoidea).

The amino acid sequence of the myoglobin of the South American Night Monkey, Aotes trivirgatus, is identical to that of the marmoset (Callithrix jacchus [1]) except for residue 21 which is isoleucine in the marmoset, like in all other anthropoids, but valine in Aotes. Analysis of a possible pathway of the evolution of Aotes myoglobin using 18 known primate myoglobin sequences [2-5] supports the classification of the Night Monkey within Anthropoidea and Platyrrhini but it indicates that this species might be more closely related to the marmoset (family Callitrichidae) than to the family Cebidae as a member of which it is commonly classified.

Amino Acid Sequence↗
PubMed1995

Thalidomide and the immune system. 4. Down-regulation of the CD26 receptor, probably involved in the binding of HIV components to T cells in primates.

Thalidomide (Thd) is capable of down-regulating the CD26 receptor on CD4+ lymphocytes after treatment of healthy volunteers. Similar effects are observed when marmosets (Callithrix jacchus) are treated with Thd. The Ta1 epitope of the CD26 receptor has recently been shown to bind the HIV-1 Tat trans-activating protein, and CD26 has also been suggested to be a coreceptor for the binding of the V3 loop of the gp120 HIV envelope protein. This might provide a hint for possible therapeutic interventions.

Animals↗
PubMed1995

Proliferative capacity of marmoset lymphocytes after tetanus vaccination and lack of 2,3,7,8-tetrachlorodibenzo-p-dioxin to reduce a booster effect.

Marmosets (Callithrix jacchus) were vaccinated with tetanus toxoid and boostered 3 months and 1 year following the initial immunization. During this period, the proliferative response of lymphocytes (3H-thymidine incorporation) to the recall antigen was measured in vitro in blood samples 7 times. The experimental procedure proved to be suitable to monitor a defined but complex function of the immune system, and to assess possible substance-induced alterations with minimal stress or discomfort for the non-human primates. As a first example, a possible interference by a single very small dose (100 ng/kg body weight) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) given at the time of the second booster was evaluated. No reduction in the in vitro response of the lymphocytes to recall antigen was observed under the experimental conditions used, and the extent of the 3H-thymidine incorporation was not significantly different in the groups. When the ratio of the responses between the first and the second booster was taken as a measure, there was a slight but statistically significant increase in this ratio for the lymphocytes of the TCDD-treated marmosets over that of reference animals. The limitations of these attempts to develop a test system and evaluate a substance-induced effect, and possible improvements of the test, e.g. with multivaccination, are discussed. It is suggested to use this approach also after routine multivaccination in children to assess possible substance-induced effects on immunological variables. This would allow an excellent comparison of experimental and clinical data obtained in primates with an identical technology.

Animals↗
PubMed1996

Down-regulation of adhesion receptors on cells of primate embryos as a probable mechanism of the teratogenic action of thalidomide.

In spite of ongoing speculation, there has been no evidence that adhesion receptors are expressed on the cells of mammalian embryos. In this report, we provide the first proof that a variety of such receptor (beta 1-, beta 2-, and beta 3-integrins and selectin) are indeed expressed on cells of essentially all primordia of marmoset embryos at early organogenesis (developmental stages 11 to 13, or even earlier). Treatment with low doses (20 or as little as 1 mg/kg body weight) of a highly teratogenic derivative (EM12) of thalidomide, the most notorious human teratogen, triggers a dramatic and statistically highly significant down-regulation of several surface adhesion receptors (e.g. CD11a/CD18, CD49d/CD29, CD61, etc.) on early limb bud cells and on cells of some other primordia during early organogenesis of embryos of a primate (marmoset, Callithrix jacchus). Some of these receptors almost disappear, or they are expressed at a lower epitope density in the exposed embryos. These down-regulations of surface adhesion receptors may be expected to alter cell-cell- and cell-extracellular matrix interactions, and they are suggested to be a long-sought primary mechanism of the teratogenic action of thalidomide-type substances.

Animals↗
PubMed1996

Thalidomide derivatives and the immune system. 6. Effects of two derivatives with no obvious teratogenic potency on the pattern of integrins and other surface receptors on blood cells of marmosets.

The two thalidomide (Thd) derivatives beta-EM12 and phthalimidophthalimide (Phtpht), which exhibit no obvious teratogenicity, were tested for their ability to induce changes in the pattern of lymphocyte subpopulations, and especially changes in integrin receptors, in marmosets (Callithrix jacchus). Previously, Thd and its highly teratogenic derivative alpha-EM12 had been found to alter the expression of adhesion molecules, such as CD2 (LFA-2) or CD11a/CD18 (LFA-1). None of these typical effects on adhesion receptors were observed following administration of the relatively high daily doses of 50 mg/kg body wt beta-EM12 and Phtpht. Nevertheless, there were some minor effects, such as alterations in the receptor density on peripheral blood mononuclear cells, which were often contrary to the effects induced by Thd. Mainly affected were: CD8 cells, B cells bearing the CD54 receptor and CD4 cells bearing the CD56 (NCAM) surface marker. We observed an increase in the receptor density of CD11c (p150,95) on monocytes with Phtpht but not with beta-EM12. The inability of the two substances with no obvious teratogenic potential to typically modify beta 2-integrin receptors on white blood cells at comparatively high doses is consistent with our hypothesis, that the teratogenicity of Thd may also be linked to alterations in the expression of adhesion molecules.

Animals↗
PubMed1994

Social and reproductive influences on plasma cortisol in female marmoset monkeys.

Subordinate female common marmosets (Callithrix jacchus) undergo ovulation suppression and exhibit low plasma cortisol levels compared to the dominant, breeding female. To determine whether this cortisol difference is mediated by the differential reproductive consequences of social status, we monitored plasma progesterone and cortisol in 32 adult female marmosets while they were housed in heterosexual pairs, during the first 3 days of heterosexual group formation, and while animals were housed in established social groups. Cortisol levels prior to group formation were significantly higher in females exhibiting cyclic ovulatory activity than in anovulatory females but were not predictive of social status. Subsequently, when animals were housed in established social groups, dominant (cyclic) females had significantly higher cortisol levels than did subordinate (anovulatory) females. Cortisol levels differed between the pre and postgroup formation conditions only in animals that underwent a corresponding onset or termination of ovulatory cyclicity. Cortisol differences between dominant and subordinate female marmosets therefore appear to be associated with differences in reproductive function rather than with social status per se.

Animals↗
PubMed1985

Immunization of marmosets with Trypanosoma cruzi cell surface glycoprotein (GP90).

Marmosets (Callithrix jacchus) have been immunized with a vaccine comprising a Trypanosoma cruzi 90K cell surface glycoprotein and the adjuvant saponin; a combination previously shown to be protective in mice. Immunization was by two s.c. injections one month apart and non-lethal challenge of homologous Y strain T. cruzi was given one month after the booster immunization. No anti-T. cruzi antibodies were detected after the first immunization but high levels developed after boosting. Immunization caused a significant decrease in the levels of acute phase blood parasitaemia, however, both immunized and control animals remained xenodiagnosis positive 60 weeks after infection. No ECG aberrations, histopathological lesions or anti-tissue antibodies were detected in infected marmosets.

Adjuvants, Immunologic↗
PubMed1996

Distribution of hippocampal mineralocorticoid and glucocorticoid receptor mRNA in a glucocorticoid resistant nonhuman primate.

Glucocorticoids regulate the activity of the hypothalamic-pituitary-adrenal axis through both mineralocorticoid (MR) and glucocorticoid (GR) receptors in the hippocampus. In addition, glucocorticoids down-regulate hippocampal expression of MR and GR mRNA and protein, presumably decreasing their own effect. Marmosets are a New World primate characterized by extraordinarily high levels of circulating ACTH and cortisol. The relative glucocorticoid insensitivity of these animals to their massive levels of glucocorticoids was attributed to a decreased affinity of their GR for glucocorticoids, as well as a compromised ability of this receptor to transactivate glucocorticoid-responsive genes. The lack of mineralocorticoid excess, on the other hand, was attributed to a renal MR which responded poorly to cortisol, but normally to aldosterone. The purpose of this study was to examine MR and GR mRNA expression in the marmoset (Callithrix jacchus jacchus) hippocampus. Overall, steady state levels of both MR and GR mRNA were elevated in all of the hippocampal subfields of the marmoset, and this was obvious in rough comparisons with those of a typical glucocorticoid-sensitive Old World primate, the rhesus monkey (Macaca mulata). Notable were the extremely high levels of GR mRNA in the dentate gyrus and field CA3 of the marmoset. The GR mRNA density distribution of the marmoset also appeared to differ from that in the rhesus and from those previously reported in rats and humans. These findings suggest that there is a compensatory elevation of MR and GR mRNAs in the marmoset hippocampus, which appears to be the result of target tissue resistance to glucocorticoids and inappropriate down-regulation by the elevated, but ineffective, circulating cortisol.

Animals↗
PubMed1993

Structure and evolution of the polymorphic photopigment gene of the marmoset.

The marmoset Callithrix jacchus jacchus, is typical of a New World monkey in exhibiting a polymorphism of photopigments in the middlewave to longwave (535-565 nm) region of the spectrum. The single X-linked opsin gene that encodes the protein component of these pigments is present in three allelic forms producing, in marmosets, pigments with maximum sensitivities at about 543, 556 and 563 nm. All male monkeys are dichromats, whereas females may be either dichromats or trichromats. A cDNA sequence corresponding to the 563 form of this gene is reported, together with partial genomic DNA sequences of exons 2, 3, 4 and 5 of all three alleles. The origin of these sequences and their divergence from the middlewave- and longwave-sensitive pigments of man is discussed from both a functional and an evolutionary standpoint.

Amino Acid Sequence↗
PubMed1994

A simple automated test to measure exploratory and motor activity of marmosets.

An automated device is described to test the exploratory and motor activity of common marmosets (Callithrix jacchus). The device consists of four boxes interconnected by PVC tubes. The presence of an animal in a box is detected by a photocell. Calibration takes place with an electric model train. Movements of the animal from one box to another are detected by disappearance from one and appearance in another box. The apparatus is linked to a PC. The effects of two doses of methamphetamine and of pentobarbital are shown.

Animals↗
PubMedDate not supplied

Effects of low doses of cholinesterase inhibitors on behavioral performance of robot-tested marmosets.

To investigate at which dose levels undesirable effects started, behavioural performance and several physiological parameters were measured in marmosets (Callithrix jacchus) after soman (1.75 and 3.5 micrograms/kg), sarin (3 and 6 micrograms/kg), physostigmine (10 and 20 micrograms/kg), and pyridostigmine (200 and 400 micrograms/kg). Effects on performance were investigated with a discrete-trial, two-choice visual discrimination task and a hand-eye coordination task. The former test appeared more sensitive to disruption than the hand-eye coordination task. "Motor speed" was not disrupted by any of the four compounds. However, "choice time" as well as "no attempts" increased and were clearly more disturbed by soman and physostigmine than by sarin and pyridostigmine. All effects had disappeared after 24 h. Except for a small effect of sarin on heart rate and blood pressure, none of the cholinesterase (ChE) inhibitors affected a number of physiological parameters at behavioural effective does that caused a profound ChE inhibition in blood. Take together, these results strongly suggest that both soman and physostigmine may interfere with higher CNS functions at low dose levels. These effects may go undetected because physical signs are absent.

Animals↗