Video-task acquisition in rhesus monkeys (Macaca mulatta) and chimpanzees (Pan troglodytes): A comparative analysis

This study describes video-task acquisition in two nonhuman primate species. The subjects were seven rhesus monkeys (Macaca mulatta) and seven chimpanzees (Pan troglodytes). All subjects were trained to manipulate a joystick which controlled a cursor displayed on a computer monitor. Two criterion levels were used: one based on conceptual knowledge of the task and one based on motor performance. Chimpanzees and rhesus monkeys attained criterion in a comparable number of trials using a conceptually based criterion. However, using a criterion based on motor performance, chimpanzees reached criterion significantly faster than rhesus monkeys. Analysis of error patterns and latency indicated that the rhesus monkeys had a larger asymmetry in response bias and were significantly slower in responding than the chimpanzees. The results are discussed in terms of the relation between object manipulation skills and video-task acquisition.     

The cerebral artery in cynomolgus monkeys (Macaca fascicularis)

Cerebral artery structure has not been extensively studied in primates. The aim of this study was to examine the cerebrovascular anatomy of cynomolgus monkeys (Macaca fascicularis), which are one of the most commonly used primates in medical research on human diseases, such as cerebral infarction and subarachnoid hemorrhage. In this study, we investigated the anatomy and diameter of cerebral arteries from 48 cynomolgus monkey brain specimens. We found three anatomical differences in the vascular structure of this species compared to that in humans. First, the distal anterior cerebral artery is single. Second, the pattern in which both the anterior inferior cerebellar artery and posterior inferior cerebellar artery branch from the basilar artery is the most common. Third, the basilar artery has the largest diameter among the major arteries. We expect that this anatomical information will aid in furthering research on cerebrovascular disease using cynomolgus monkeys.     

Mobility of surrogate mothers and persistent neophobia in cynomolgus monkeys (Macaca fascicularis)

In search of the relevant difference between mother rearing and surrogate rearing with respect to the emergence of neophobic behavior in macaques, we tested the hypothesis that mobility of surrogate mothers prevents the development of neophobic behavior in cynomolgus macaques. The experimental group consisted of ten surrogate-reared subjects which during their first year got rides on surrogate mothers moving through the cage. The control group consisted of nine subjects reared with immobile surrogate mothers. Between the age of 7 and 27 months the reactions to two different novel objects were tested. First exposure to one object occurred at 6 months of age and to the other object at 20 months. The kind of object and the age of first exposure made no difference. Contrary to our expectations mobility of surrogates did not affect the incidence of neophobia: most subjects in both groups persistently avoided the objects. This finding seems to support Hofer's hypothesis that the mother acts as a regulator of the infant's behavior and physiology.     

Spontaneous diabetes mellitus in cynomolgus monkeys (Macaca fascicularis)

Glucose tolerance tests were performed with fourteen cynomolgus monkeys. They were divided into two groups with regard to the serum glucose level at the time of routine health-examination. Nine of them had normal glucose level (below 123 mg/dl, the normal group) and the other five monkeys exhibited hyperglycemia (the abnormal group). Fifty per cent glucose solution was administered into the saphenous vein at a dose of 4 ml/head. Blood samples were taken just before and 5, 10, 20, 30, 60 and 120 minutes after the glucose administration. K-value (K = 0.693/t 1/2 X 100) as the decreasing rate of serum glucose during from 5 to 60 minutes after the administration was calculated. Average K-value for eight monkeys of the normal group was 3.12 +/- 0.48. Both immunoreactive insulin level (IRI) and C-peptide immunoreactivity (CPR) increased just after the glucose administration and began to decrease 5 to 30 minutes after the administration in all the eight animals. Remaining one animal (No. 009) of the normal group showed 1.03 in K-value. For the abnormal group, K-value averaged 0.75 +/- 0.25. IRI was slightly higher in this group than in the 8 monkeys of the normal group. Furthermore, the abnormal group did not show any definite change of a certain trend in IRI and CPR. In conclusion, the former 8 monkeys were judged to be normal in the function of pancreatic beta-cells, and the latter 5 monkeys and No. 009 monkey were judged to be suffering from type II (noninsulin dependent) diabetes mellitus at different stages of the disease.     

CD3 polymorphism in cynomolgus monkeys (Macaca fascicularis)

Cynomolgus monkeys were divided into two groups in terms of the reactivity of their lymphocytes with the FN18 monoclonal antibody, which is directed to the CD3 of rhesus monkeys. It was shown that 24 (12.2%) out of 196 monkeys did not have lymphocytes that reacted with the FN18, although T cells from those animals responded well to mitogenic stimulation. We have determined the nucleotide sequences of the CD3delta, CD3gamma, and CD3epsilon chains and found that two amino acids of the CD3epsilon chain of the FN18 non-reactive monkeys were different when compared with the FN18 reactive monkeys. Our results indicated that the CD3epsilon molecule of cynomolgus monkeys is polymorphic at the epitope level, which is recognized by the FN18 monoclonal antibody.     

Cryopreservation of spermatozoa from cynomolgus monkeys (Macaca fascicularis)

Three egg-yolk diluents, which have been used successfully in cryopreservation of human spermatozoa, were compared for their ability to protect macaque semen against cryodamage. TEST (Tes + Tris + egg yolk), TEST with 20% skim milk (TSM), and egg yolk-citrate (EYC), each with 3 or 5% glycerol were compared using 12 ejaculates from 6 male cynomolgus macaques. Computer-aided analysis of sperm motion was used to determine the percentage motility (%M), curvilinear velocity (VCL), and linearity (LIN) of spermatozoa after thawing. The supravital stain Hoechst 33258 and a fluoresceinated pea lectin were used to determine the % of viable spermatozoa with intact acrosomes. TSM and TEST were superior to EYC in terms of % M and of % viable, acrosome-intact spermatozoa. TSM and TEST produced equivalent VCL and LIN values, while EYC had clearly reduced VCL and LIN. There were no interactions between diluent and glycerol level. The 3% glycerol level gave superior results to 5% glycerol for %M. EYC, which is widely used for cryopreservation of human spermatozoa, was not suitable for cynomolgus monkey semen. Artificial insemination with semen cryopreserved in TSM resulted in a healthy, full-term infant.     

Enzootic hepatitis A infection in cynomolgus monkeys (Macaca fascicularis)

During a toxicology study in cynomolgus (long-tailed or crab-eating) monkeys (Macaca fascicularis), a randomly distributed incidence of significantly increased hepatic enzyme activity was observed. Premedication hepatic enzyme activity in all monkeys of this study was normal, but increased alanine aminotransferase (ALT) activity was found in 4 of the 24 animals 2 weeks after initiation of the study and in 10 of 24 at 4 weeks. A drug-related effect was considered unlikely initially because the increases were not doserelated, and a 3-year review of 655 cynomolgus monkeys revealed a 15–20% incidence of increased hepatic enzyme activity. Good correlation was subsequently established between increased hepatic enzyme activity, active hepatitis A virus (HAV) infection, and histomorphologic confirmation of hepatitis (chronic periportal inflammation). Follow-up viral serodiagnostic screening of resident macaques revealed an overall incidence of anti-HAV IgG in 80% (155/193) of cynomolgus and in 70% (14/20) of rhesus monkeys. Serial screening demonstrated that several initially negative monkeys became seropositive for anti-HAV IgG, and a few acquired active infection (anti-HAV IgM). Among newly acquired cynomolgus monkeys, 2.5% (2/80) had an acute HAV infection, and 35% (28/80) eventually tested positive for anti-HAV IgG while quarantined in the primate facility. The characterization of an enzootic HAV infection in incoming monkeys posed a significant risk for the primate colony and handlers. Rigorous sanitation, isolation, and quarantine procedures, including personnel training and additional protective clothing for personnel working in the primate colony, reduced tho potential for transmission and arrested the outbreak. Experimenters should be cautious in ascribing toxicity to a test article based solely on increased hepatic enzyme activity associated with chronic periportal inflammation.     

Modeling depression in adult female cynomolgus monkeys (Macaca fascicularis)

Depressive disorders are prevalent, costly, and poorly understood. Male rodents in stress paradigms are most commonly used as animal models, despite the two-fold increased prevalence of depression in women and sex differences in response to stress. Although these models have provided valuable insights, new models are needed to move the field forward. Social stress-associated behavioral depression in adult female cynomolgus macaques closely resembles human depression in physiological, neurobiological, and behavioral characteristics, including reduced body mass, hypothalamic-pituitary-adrenal axis perturbations, autonomic dysfunction, increased cardiovascular disease risk, reduced hippocampal volume, altered serotonergic function, decreased activity levels, and increased mortality. In addition, behaviorally depressed monkeys also have low ovarian steroid concentrations, even though they continue to have menstrual cycles. Although this type of ovarian dysfunction has not been reported in depressed women and is difficult to identify, it may be the key to understanding the high prevalence of depression in women. Depressive behavior in female cynomolgus monkeys is naturally occurring and not induced by experimental manipulation. Different social environmental challenges, including isolation vs. subordination, may elicit the depression-like response in some animals and not others. Similarly, social subordination is stressful and depressive behavior is more common in socially subordinate monkeys. Yet, not all subordinates exhibit behavioral depression, suggesting individual differences in sensitivity to specific environmental stressors and enhanced risk of behavioral depression in some individuals. The behavior and neurobiology of subordinates is distinctly different than that of behaviorally depressed monkeys, which affords the opportunity to differentiate between stressed and depressed states. Thus, behaviorally depressed monkeys exhibit numerous physiological, neurobiological, and behavioral characteristics same as those of depressed human beings. The nonhuman primate model represents a new animal model of depression with great promise for furthering our understanding of this prevalent and debilitating disease and identifying novel therapeutic targets.     

Adoption success under single-cage conditions by cynomolgus macaque mothers (Macaca fascicularis)

Retrospective data were studied to determine the success of experimental adoption by 122 cynomolgus macaques kept in individual cages at the Tsukuba Primate Center. The four types of adoption procedures included (1) singletons adopted after weaning (SAW)—21 cases; (2) singletons adopted after stillbirth (SAS)—20 cases; (3) singletons adopted after forced separation of the biological infant during the nursing period (SAF)—4 cases; and (4) adoption of a second “twin” while still nursing a biological infant (TA)—77 cases. Adoption was defined as successful if the mother nursed the foster infants for at least 7 days. Success rates (percent) were 47.6 for SAW, 75 for SAS, 100 for SAF, and 74 for TA. Success was affected by the postbirth stage of foster mothers at adoption but not by foster infant age or sex.     

Yersiniosis in a breeding unit of Macaca fascicularis (cynomolgus monkeys)

2 outbreaks of acute fatal enteric disease involving 20 animals in a breeding unit of approximately 200 cynomolgus monkeys were diagnosed as yersiniosis; Yersinia pseudotuberculosis was isolated from 50% of the clinically affected animals. Post-mortem findings included enlarged mesenteric lymph nodes with some enterocolitis and necrotic foci in liver and spleen. Approximately 7% of clinically healthy monkeys were found to be excreting Y. pseudotuberculosis and a further 5% Y. enterocolitica. Rectal swabs, though less convenient, were better than faecal samples for the detection of Yersinia spp. in 'healthy' monkeys. Efficiency of the cold saline technique and direct plating for isolating Yersinia spp. were compared. It is thought likely that the infection was introduced into the unit by asymptomatic infected monkeys.     

Microsatellite variation in two subspecies of cynomolgus monkeys (Macaca fascicularis)

To estimate the genetic variability of two subspecies of cynomolgus monkeys (Macaca fascicularis fascicularis and M. f. aurea) using microsatellite markers, 26 microsatellite markers were selected from previous reports. Seventeen markers showed high polymorphism in a subset of monkeys and were used for the assessment of genetic diversity in the larger sample. The effective number of alleles, the polymorphism information content (PIC) and the expected heterozygosity of M. f. aurea monkeys were all statistically significantly higher than those of M. f. fascicularis monkeys (P < 0.05), suggesting the M. f. aurea monkeys had a higher degree of genetic variation than the M. f. fascicularis monkeys. Substantial differences in allele distribution were also detected between the two subspecies of cynomolgus monkeys. Private alleles restricted to the M. f. fascicularis or the M. f. aurea monkeys were found throughout the selected 17 loci. These private alleles may allow the discrimination of the two subspecies of cynomolgus monkeys. The selected markers could also be used to estimate the genetic variation for other subspecies of cynomolgus monkeys. Further work using additional animals obtained from native or independent sources will be important for a more complete understanding of the genetic differences between these two subgroups.     

Familial early onset macular degeneration in cynomolgus monkeys (Macaca fascicularis)

The mode of inheritance of macular degeneration was determined with 45 cynomolgus monkeys (18 females and 27 males) who were the offspring of one breeding male with typical macular degeneration. In the first generation, 27 offspring (10 females and 17 males) were born from mating between the macular degeneration-affected founder male and 5 normal female breeders. Among them, 18 monkeys (9 females and 9 males) were judged as having macular degeneration (affected). Next, the distribution of affected offspring was examined with 18 offspring who were born from 3 different mating pairs, normal vs normal, affected vs normal and affected vs affected, when they became 2 years old. All of the 9 monkeys (4 females and 5 males) obtained from the 2 pairs of normal vs normal were normal. On the other hand, 6 affected monkeys (3 females and 3 males) were detected in 8 offspring from the mating pair of affected vs normal, and the single offspring produced by the mating pair of affected vs affected was affected. These results showed that this degeneration must be early onset familial macular degeneration controlled by autosomal dominant gene(s).     

Pregnancy-induced sclerosis in the myometrial vessels of cynomolgus monkeys (Macaca fascicularis)

Sclerotic changes were found histologically in the myometrial vessels of 27 out of 33 cynomolgus monkeys (Macaca fascicularis). The sclerosis was composed of fibrous proliferations and intimal thickening. These changes were not observed in nulliparous cases, but were found only in multiparous ones. The findings suggest that the sclerotic changes in the myometrial vessels of cynomolgus monkeys are a pregnancy-induced phenomenon.     

Age assessment in infant crab-eating monkeys (Macaca fascicularis) based on tooth development

Tooth development was studied in 13 Macaca fascicularis monkeys with known dates of birth. Regular intra-oral examination was carried out and standardized lateral radiographs were collected from 27 until 150 weeks of age under general anaesthesia.
Three stages of tooth development were determined radiographically: onset of crypt formation, onset of mineralization, and crown completion. A fourth stage, the emergence, was determined clinically. Developmental stages were recorded for six mandibular and five maxillary teeth.
The ages of emergence of the permanent teeth and the developmental stages of the third molars showed the largest variation. A significant sex difference with earlier maturation in males was found for the start of crypt formation of the maxillary permanent canines and the maxillary second premolars, and for the start of mineralization of the maxillary permanent canines.
The data provide a tool by which chronological age can be assessed of Macaca fascicularis monkeys between 30 and 80 weeks of age. Owing to an interphase of about one year without significant developmental features in the dentition, age assessment based on tooth development cannot be performed from about 80 to 130 weeks of age. Age assessments are possible for the period between 130 and 150 weeks of age. However, in this period the reliability of the data is lower due to larger time intervals and standard deviations.     

The serodiagnosis of Campylobacter infection in infant cynomolgus monkeys (Macaca fascicularis) 2 to 18 weeks old by enzyme-linked immunosorbent assay

We established the enzyme-linked immunosorbent assay (ELISA) for detecting antibodies to Campylobacter and applied it in defining the period of the primary infection of Campylobacter in infant cynomolgus monkeys (Macaca fascicularis). The antibody to Campylobacter spp. could be detected with only 0.25 mul of serum by using commercially available antigens and anti-cynomolgus monkey IgG antibody conjugated with alkaline phosphatase. The inhibition experiments using extracts of C. jejuni, C. fetus and Yersinia enterocolitica demonstrated that the established ELISA system could detect species-specific anti-C. jejuni and anti-C. fetus antibodies. The levels of antibodies to both C. jejuni and C. fetus were high in 2 weeks old infant cynomolgus monkeys, rapidly decreasing until 6 to 14 weeks of age. This result indicates that the antibodies detected in 2 week old infants were IgG antibodies of maternal origin transferred through placenta. The C. jejuni was isolated from infants when the level of maternal antibody became the lowest. Infant cynomolgus monkeys obviously developed IgG antibodies to C. jejuni within 4 weeks after infection. On the other hand, no antibody response to C. jejuni was found in two infants from which it could not be isolated throughout the observation period. As regards C. fetus infection, infants showed a poor antibody response although it was more frequently isolated than C. jejuni. In conclusion, the ELISA system established in the present study is useful for the serological diagnosis of C. jejuni infection during infancy in the cynomolgus monkey.     

Active immunization of cynomolgus monkeys (Macaca fascicularis) with porcine zonae pellucidae

Cynomolgus monkeys (Macaca fascicularis) were immunized with porcine zonae pellucidae to assess the possible antifertility effects of the zona antibodies. Serum antibody titers were evaluated utilizing a rapid solid-phase radioimmunoassay. Six of twelve monkeys conceived 6 to 10 wk after vaccination. All monkeys reached maximal antiserum titers by the time of conception, although the six animals that did not conceive had considerably lower antibody titers. Further pregnancies did not occur until antibody level had declined markedly, 8 mo after last immunization. The menses of all but one of the remaining six monkeys were interrupted intermittently. Also, the usual midcycle elevated estradiol levels were absent for several cycles. Both menses and midcycle estradiol peaks were reestablished in all but one monkey 3 to 5 mo after the last booster was given. Two monkeys conceived when serum antibody levels dropped to one fourth of maximal, but both had a still birth. Histological observations showed accumulation of luteal tissue and massive atresia of small follicles at the end of the study (18 mo). We conclude that through heteroimmunization with porcine zona pellucida monkeys can become infertile and that this condition is reversible. Because the zona preparation used in this study appeared to contain traces of nonzona material, it was not possible to determine whether the menstrual irregularities and oocyte atresia that we observed were owing to immunological effects on the zona itself or to the production of antibodies against other ovarian components.     

Cryopreservation of epididymal spermatozoa collected by needle biopsy from cynomolgus monkeys (Macaca fascicularis)

We have examined the motility, morphology, and cryopreservation of epididymal spermatozoa collected by needle biopsy from cynomolgus monkeys (Macaca fascicularis). At collection, epididymal sperm (23 x 10(6) +/- 4 x 10(6) sperm/sample; 611 x 10(6) +/- 116 x 10(6) sperm/ ml; n = 18) were alive (79 +/- 2%), motile (67 +/- 2%), and exhibited intact membranes (65 +/- 2%). Sperm maintained at room temperature in handling medium exhibited decreased motility over time, but head-to-head agglutination was limited. Tris egg-yolk extender containing 6% glycerol and dimethylsulfoxide (DMSO) did not significantly affect functional morphology, whereas extender containing propanediol significantly reduced motility, survival, and membrane integrity. Cryostorage reduced all measures of functional morphology independent of cryoprotectant. Post-thaw motility was superior for glycerol and DMSO compared to propanediol. Variation in glycerol concentration (4, 6, and 8%) produced equivocal effects on sperm functional morphology post-thaw. Needle biopsy may be a useful technique for laboratory and field-based collection of spermatozoa from nonhuman primates.