The embryology of the common marmoset (Callithrix jacchus)

Earlier studies have noted the unusual placental anatomy of marmosets and the high frequency of biovular, synchorial twinning. The maintenance of a captive colony of Callithrix jacchus has enabled further studies to be made of embryonic development in this species. Thirty-six embryos from seventeen pregnancies were examined in detail and assigned to horizons on the basis of Streeter's classification of external form and internal structure. The specimens represented tha major part of the embryonic period and, with few exceptions, the structural development of the marmoset closely resembled that of the other primates that have been described. Marmoset embryos of a given horizon were consistently shorter than those of man. The timing of morphogenesis in C. jacchus was different from that observed in man and other primates. There was a considerable delay in early embryogenesis in the marmoset, although subsequent to stage XI, development proceeded at approximately the same rate as other primates. The available evidence suggested that this anomaly was not due to delayed implantation or embryonic diapause but to a generally slower rate of early development. The evolution of synchorial twinning is considered as a possible reason for this mode of development.     

Vasopressin in the forebrain of common marmosets (Callithrix jacchus): studies with in situ hybridization, immunocytochemistry and receptor autoradiography

The distribution of vasopressin (AVP) producing cells, their projections and AVP receptors was examined in the brain of common marmosets (Callithrix jacchus) using in situ hybridization, immunocytochemistry and receptor autoradiography. Clusters of cells labeled for AVP mRNA or stained for AVP immunoreactivity (AVP-ir) were found in the paraventricular (PVN), supraoptic (SON) and suprachiasmatic nuclei (SCN) of the hypothalamus. Scattered AVP producing cells were also found in the lateral hypothalamus and the bed nucleus of the stria terminalis (BST). Neither AVP mRNA-labeled nor AVP-ir cells were detected in the amygdala. Although AVP-ir fibers were evident outside of the hypothalamic-neurohypophyseal tract, a plexus of fibers in the lateral septum, as observed in the rat brain, was not detected. Receptor autoradiography using 125I-linear-AVP revealed specific binding for AVP receptors in the nucleus accumbens, diagonal band, lateral septum, the BST, SCN, PVN, amygdala, anterodorsal and ventromedial nucleus of the hypothalamus, indicating sites for central AVP action in the marmoset brain. Together, these data provide a comprehensive picture of AVP pathways in the marmoset brain, demonstrating differences from rodents in the distribution of cell bodies, fibers and receptors.     

The common marmoset (Callithrix jacchus) as a model for neuroleptic-induced acute dystonia

To examine whether acute dystonia is induced by neuroleptic treatment, common marmosets were treated with haloperidol orally twice a week over 25 weeks until dystonic behavior was elicited. Movement disorders such as acute dystonia were observed 6 weeks after the initial treatment, and had appeared in all treated animals by 25 weeks. Once these movement disorders were induced, they consistently reappeared after further treatment with haloperidol, and once haloperidol dosing was discontinued, the episodes vanished. Then, various neuroleptic drugs (bromperidol, chlorpromazine, risperidone thioridazine, sulpiride, tiapride, and clozapine) or a nonneuroleptic drug (diazepam) were administered orally instead of haloperidol in the above animals. All the neuroleptic drugs except for clozapine elicited similar abnormal behavior, while diazepam failed to induce any dystonia. An anticholinergic drug, trihexyphenidyl, which is known to reduce acute dystonia in patients, was also given orally to the above haloperidol-sensitized animals, followed by further treatment with haloperidol 30 min later. This clearly suppressed the induction of dystonia by haloperidol. The similarity between these findings for haloperidol-pretreated common marmosets and clinical findings suggests that the present model is useful for predicting the potential of antipsychotics to induce acute dystonia in humans.     

Unusual case of metabolic bone disease in a common marmoset (Callithrix jacchus)

Metabolic bone disease was diagnosed in an 11-month-old female common marmoset (Callithrix jacchus). It was depressed, reluctant to move, and was cachectic and small for its age. Laboratory findings included anaemia, azotaemia and an inverse calcium to phosphorus ratio. The radiological findings showed simultaneous signs of osteomalacia and soft-tissue calcification. There was decreased bone density with lytic areas in the pelvis and femur, and severe bilateral nephrocalcinosis. Postmortem examination revealed marked focal dystrophic calcification of the epi- and myocardium. Calcium and vitamin D3 deficiency (nutritional secondary hyperparathyroidism) was the most likely cause of the osteomalacia.     

Hand preference during behavioral tests and spontaneous activity in two species of common marmoset (Callithrix jacchus and Callithrix penicillata)

Hand preference in two adult C. jacchus (one male and one female) and five C. penicillata (three adult females and two 70-day-old male and female infants) was examined in this study. Animals were housed in large wire mesh cages and daily tested twice during 40 consecutive days in 15-minute experimental sessions. Tests were carried out with dog food pellets and were as follows: 1) food taking from a glass cylinder (12 cm long x 5 cm diameter), 2) food taking from an opaque plastic flask (11 cm long x 9.5 cm diameter) behind wire mesh, 3) food taking under the cage floor and 4) spontaneous activity (food manipulation, self-grooming and scratching behavior, and grasping wire mesh). It was observed that 1) subjects exhibit a high manual ability in all testing conditions, 2) hand biases occurred, but the subjects either reversed hand preference or the preference was ambiguous as the performances are examined in a longitudinal perspective, 3) hand biases were clearly more visible in test 1, which may be due to the complexity of this task itself, 4) hand biases were not similar in all testing conditions--i.e., subjects were left--in one test and right-handed in another-, and 5) the main results were very similar in both C. jacchus and C. penicillata and seem to be not dependent on either sex or age.     

Effects of recombinant human interleukin 6 (rhIL-6) in marmosets (Callithrix jacchus). 1. General toxicity and hematological changes

The physiological and toxicological properties of recombinant human interleukin 6 (rhIL-6) were assessed in marmoset monkeys (Callithrix jacchus). Two experimental series were performed with daily subcutaneous administration: (a) 5 or 1000 micrograms rhIL-6/kg per day for three weeks and (b) 25, 100 or 500 micrograms rhIL-6/kg per day for 3 months. RhIL-6 was well tolerated and did not induce fever or any other non-specific signs of toxicity. The main findings were: (1) A two- to threefold increase in platelet counts at 2-4 weeks, which decreased following further continuous rhIL-6 administration; (2) increase in total white blood cells between 1 and 4 weeks of administration, including an absolute increase in granulocytes (including band forms) and basophils. A change in the number of monocytes was not detected; (3) an increase in total red blood cells, which peaked at 4 weeks, sustained elevation of red cell distribution width and a slight decrease in hemoglobin between week 1 and 4, concurrent with a distinct decrease in mean corpuscular hemoglobin at 4 weeks. This effect persisted for 9 weeks in the 100 micrograms/kg and 500 micrograms/kg groups; (4) decrease in plasma AST activity and increase in plasma protein concentration after 2 weeks of treatment; (5) no clinical or biochemical signs of renal glomerular dysfunction; (6) RhIL-6 after s.c. administration was detectable in the plasma, peak levels (mean values +/- SD) of 9.4 +/- 6.3 and 72.4 +/- 7.7 ng/ml were measured after a single dose of 100 or 1000 micrograms/kg; (7) antibodies against rhIL-6 developed within 2 weeks, increased during administration and neutralized the biological effect of rhIL-6 progressively from 4 to 9 weeks. In conclusion, aside from a mild anemia, rhIL-6 was well tolerated in marmosets and had a profound and sustained effect on thrombopoiesis. Due to the formation of neutralizing antibodies, the chronic biological effect of rhIL-6 is lost in marmosets and studies beyond 4 weeks are rendered less meaningful. The analyses of antibody formation, induction of acute phase proteins, histological changes and alterations on lymphocyte receptors will be reported in two following publications.     

The distribution of p75 neurotrophin receptor-immunoreactive cells in the forebrain of the common marmoset (Callithrix jacchus)

Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of prostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In spite of long-standing speculation, definitive roles of PGs in various events of early pregnancy remain elusive. We demonstrate herein that the targeted disruption of COX-2, but not COX-1, in mice produces multiple failures in female reproductive processes that include ovulation, fertilization, implantation, and decidualization. Using multiple approaches, we conclude that these defects are the direct result of target organ-specific COX-2 deficiency but are not the result of deficiency of pituitary gonadotropins or ovarian steroid hormones, or reduced responsiveness of the target organs to their respective hormones.     

The biobehavioral consequences of psychogenic stress in a small, social primate (Callithrix jacchus jacchus)

The biobehavioral consequences of psychogenic stress were examined using neuroendocrine and ethological methods in a captive colony of common marmosets (Callithrix jacchus jacchus). Specifically, hypothalamic-pituitary-adrenal (HPA) axis reactivity was evaluated as a function of gender and social status in four consecutive social environments [(1) stable heterosexual pairs; (2) isolation; (3) unstable peer groups; and (4) stable peer groups], by measuring both basal plasma cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin concentrations and responsiveness of these hormones to dexamethasone, ovine corticotropin-releasing hormone (oCRH), and ACTH1-24. Socially stressful conditions, such as isolation and peer group formation, were associated with increased HPA axis function and behavioral arousal, and individual profiles were related to gender and social status. Hormonal levels prior to group formation predicted subsequent status in peer groups. Basal morning concentrations of plasma cortisol, as well as cortisol responsiveness to dexamethasone suppression, were sensitive indices of HPA axis arousal during periods of social stress. The context-dependent development of hormonal and behavioral profiles, reminiscent of depression and/or anorexia nervosa, suggests that the common marmoset may be a useful model of psychiatric hypercortisolism.     

Expression of integrins in marmoset (Callithrix jacchus) ovary during folliculogenesis

The model of 25 children with mild Class II, Division 1 malocclusions who had their upper buccal segments moved distally with an en masse appliance were measured at the beginning of treatment and at the completion of buccal segment retraction. A reflex microscope, interfaced to a personal computer, was adapted for this purpose. A custom-made jig and linear stepping motor permitted the recording of both buccal and incisal measurements of the teeth in occlusion, as well as individual arch parameters. Software was designed to record and calculate the required measurements. The method error associated with this approach ranged from 0.01 to 0.5 mm. Results indicated that mean distal movement of the buccal segments approximated 6 mm, equivalent to a full cusp of buccal segment retraction. A small spontaneous reduction in overjet was seen. The upper arch showed spontaneous alignment and increases in width, length, and perimeter. In the lower jaw, transverse expansion was accompanied by a small increase in arch perimeter. Arch length, however, was slightly reduced. It was concluded that the system was an acceptable method of recording occlusal changes during orthodontic treatment, supplementing routine cephalometry. Furthermore, a full unit of buccal segment retraction could be expected, by using a removable appliance/headgear technique.     

Effects of click intensity and frequency on the brain-stem auditory evoked potentials in the common marmoset (Callithrix jacchus)

Brain-stem auditory evoked potentials (BAEPs) were recorded in 20 common marmosets (Callithrix jacchus) to investigate the effects of click frequency up to 99 kHz, in consideration of the higher hearing range of the marmoset, and intensity on wave forms and peak latencies. According to the results of BAEP recordings at frequencies of 4, 32, and 99 kHz, the number of components recorded was affected by the stimulus intensity and the clicks at an intensity of 80 dB peak equivalent sound pressure level (pe SPL) had the maximum number of clear components. Therefore, it was indicated that click stimulations at an intensity of 80 dB pe SPL over a broad range of frequencies appears to be useful for recording the maximum number of components in marmosets and may increase the information obtainable from BAEPs. BAEP latencies were prolonged as the stimulus intensity decreased from 100 to 50 dB pe SPL. The effects of stimulus frequency on the wave latencies and amplitudes in response to 80 dB pe SPL at frequencies between 0.5 and 99 kHz revealed various changes: the amplitude of wave I increased at 16 and 32 kHz, but that of waves III and V increased at 4-8 and 64-99 kHz. These increases in amplitudes of the waves may correlate with higher synchronous activity of the peripheral or central auditory pathways.     

Histopathological characterization of magnetic resonance imaging-detectable brain white matter lesions in a primate model of multiple sclerosis: a correlative study in the experimental autoimmune encephalomyelitis model in common marmosets (Callithrix jacchus)

N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated manipulations of the cortical cholinergic input arising from the basal forebrain differentially affect cognitive function. We used [14C]-2-deoxyglucose autoradiography in conscious rats to map the effects of excitatory amino acid agonist infusions into the nucleus basalis magnocellularis (NBM) on cerebral functional activity, as reflected by local rates of glucose utilization. Acute stimulation of NBM neurones by local infusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), 15 min before glucose use measurement, resulted in glucose use reductions in nine cortical regions innervated by NBM efferents including prefrontal, frontal, sensorimotor and cingulate cortices. NMDA infusions altered glucose use in two cortical areas. Both AMPA and NMDA markedly increased glucose use in the striatum and globus pallidus, with concomitant perturbations in striato-pallidal projection targets including the substantia nigra, entopeduncular nucleus, subthalamic nucleus and lateral habenular nucleus. In contrast, the GABAA agonist muscimol did not affect glucose use in the NBM or neocortical regions, but induced glucose use increases in several subcortical nuclei including the substantia nigra and entopeduncular nucleus. The delayed effects of excitotoxic lesions were assessed 3 weeks after basal forebrain infusions of AMPA, NMDA, ibotenate or quisqualate. Statistically significant glucose use changes only occurred in the hypothalamus after NMDA, and the NBM after ibotenate infusions, although reduced cortical metabolism was apparent following AMPA-induced lesions of the NBM. Results support a dissociation between the functional sequelae of NMDA and non-NMDA receptor-mediated events in the basal forebrain, and long-term compensatory functional adaptation following cortical denervation.     

Ubiquitin and apoptosis in the corpus luteum of the marmoset monkey (Callithrix jacchus)

The thiazolidinedione analogue troglitazone is an antidiabetic agent that improves insulin resistance in rodents and humans. Although coronary artery disease is common in patients with the insulin resistance syndrome, the effects of troglitazone on smooth muscle cells (SMC) have not been fully elucidated. We therefore examined the effects of troglitazone on cell growth and glucose uptake in human aortic SMC. Mitogen-activated protein (MAP) kinase activity and glucose transporter (Glut) 1 mRNA levels were also studied. In the absence of troglitazone, insulin (10(-7) M) caused a 2-fold increase of DNA synthesis in SMC and troglitazone suppressed the increase of DNA synthesis in a dose-dependent manner. This growth suppression was accompanied by inhibition of MAP kinase activity. On the other hand, troglitazone significantly increased Glut 1 mRNA and enhanced glucose uptake in SMC. These results suggest that troglitazone affects the insulin signaling pathways in SMC and suppresses growth while promoting glucose uptake. Our findings support the application of troglitazone as an inhibitor of SMC proliferation in patients with insulin resistance.     

Social and reproductive conditions modulate urinary cortisol excretion in black tufted-ear marmosets (Callithrix kuhli)

The endogenous metabolite, 2-methoxyestradiol (2ME), is an inhibitor of tubulin polymerization and is therefore toxic to dividing fast-growing tumor cells. Transformed cells are not equally susceptible to the effects of 2ME. In this study the effects of 1-2 microM doses of 2ME on cell cycle progression, apoptosis induction and on p53 levels were evaluated using flow cytometry in cells with different p53 status. No effect of 2ME was seen in normal human skin fibroblast strain HSF43 with wild-type (wt) p53. However, in SV40 T antigen transformed HSF43 cells (line E8T4), 2ME caused a prominent G2/M arrest, with subsequent micronuclei formation followed by apoptosis. Increased p53 levels were present in the G2/M cells. Our results suggest that 2ME, being a microtubule poison, may release the bound p53 from T antigen, and that this p53 may enhance the apoptotic effects. Two lymphoblast cell lines derived from the same donor, TK6, expressing low levels of wt p53, and WTK1, expressing high levels of mutant p53, showed similar moderate responses to 2ME at 37 degrees C. The effects included enhanced apoptosis and a modest G2/M block. No increase in p53 levels was seen. However, at the permissive temperature of 30 degrees C marked increases in apoptosis and a prominent G2/M-phase block, similar to that seen in the E8T4 cells, were present in the WTK1 cells, indicating that the high levels of mutant p53 have now become functional, enhancing the apoptotic effects initiated by 2ME.     

Parental care in marmosets (Callithrix jacchus jacchus): Development and effect of anogenital licking on exploration.

Anogenital licking of 15 infant marmosets (Callithrix jacchus jacchus) was scored from 1 to 60 days of age over four 30-min intervals per day. Mothers performed threefold the anogenital licking that fathers or siblings did. The frequency of anogenital licking was low in the first 15 days after birth, high from Days 16 to 45, and low again from Days 46 to 60. There were no significant effects of parents or sex on the amount or pattern of anogenital licking received by the offspring. The potential role of developmental changes in levels of sex hormones is discussed. Later in life, the responses of the marmosets to a fear-inducing stimulus were compared. There was a significant positive correlation between the amount of anogenital licking received and exploration of the novel stimulus. Age differences at the time of testing had no effect on exploration, nor did sex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of frontal cortex in social odor discrimination and scent-marking in female golden hamsters (Mesocricetus auratus).

Orbital/agranular insular (ORB/AI) cortex has been implicated in traditional olfactory learning tasks and social behavior but its precise role in discriminating-learning social odors is not known. Female golden hamsters received aspiration lesions of ORB/AI or dorsomedial (DM) frontal cortex and were tested for their ability to (a) discriminate between odors of individual males in a habituation-discrimination task, (b) show preferences for male over female odors, and (c) scent-mark in response to male odors. Lesioned females readily discriminated between scents of individual males. Neither lesion altered female preferences for male odors. Females with DM lesions showed increased levels of scent marking to male odors, but those with ORB/AI cortex lesions did not differ from controls. Thus, ORB/AI cortex does not appear to be critical for discrimination of odors of individuals or sex or for scent-marking responses based on these discriminations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences in social and vocal behavior between left- and right-handed common marmosets (Callithrix jacchus).

Common marmosets (Callithrix jacchus) show either a left- or right-hand preference for reaching to pick up food and they retain the same preference throughout adult life. We compared the behavior of 10 right-handed and 10 left-handed marmosets, matched for age and sex. They were presented with live crickets both when alone and when in their social group. The marmosets captured more crickets and the latency to capture the first cricket was shorter when they were in a group than when they were alone. This effect of social facilitation was significantly greater for right- than left-handed individuals. The number of vocalizations (tsik, crackle, very brief whistle, cough, and phee) produced by the left- and right-handed marmosets differed significantly: right-handed marmosets produced an increased number of all of these calls when the crickets were presented, whereas left-handed marmosets did not show a change from pretesting levels. The right-handed marmosets also produced more tsik (mobbing) calls than left-handed marmosets when they were presented with a fear-inducing stimulus and performed more head cocking and parallax movements than the left-handed marmosets. Hence, hand preference is associated with differences in exploratory and social behavior, the latter including vocal communication. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the hippocampal system in social odor discrimination and scent-marking in female golden hamsters (Mesocricetus auratus).

Female golden hamsters (Mesocricetus auratus) received aspiration lesions of the parahippocampal region (PARA) or electrolytic lesions of the fimbria-fornix (FNX) and were tested for their (a) discrimination between odors of individual males in a habituation-discrimination task, (b) preference for male over female odors, and (c) scent-marking in response to conspecific odors. Both lesion groups habituated to repeated presentations of a male's odor. However, only FNX females discriminated between scents of individual males, whereas PARA females did not. Neither lesion eliminated female preferences for male odors. Females with FNX lesions showed decreased levels of scent marking, but those with PARA lesions had more subtle deficits. Thus, the PARA, but not the subcortical connections of the hippocampus, is critical for discrimination of the odors of individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)