Biologic data of Macaca mulatta, Macaca fascicularis, and Saimiri sciureus used for research at the Fiocruz primate center

Physiological parameters of laboratory animals used for biomedical research is crucial for following several experimental procedures. With the intent to establish baseline biologic parameters for non-human primates held in closed colonies, hematological and morphometric data of captive monkeys were determined. Data of clinically healthy rhesus macaques (Macaca mulatta), cynomolgus monkeys (Macaca fascicularis), and squirrel monkeys (Saimiri sciureus) were collected over a period of five years. Animals were separated according to sex and divided into five age groups. Hematological data were compared with those in the literature by Student's t test. Discrepancies with significance levels of 0.1, 1 or 5% were found in the hematological studies. Growth curves showed that the sexual dimorphism of rhesus monkeys appeared at an age of four years. In earlier ages, the differences between sexes could not be distinguished (p < 0.05). Sexual dimorphism in both squirrel monkeys and cynomolgus monkeys occurred at an age of about 32 months. Data presented in this paper could be useful for comparative studies using primates under similar conditions.     

Leishmania donovani: cellular and humoral immune responses after primary and challenge infections in squirrel monkeys, Saimiri sciureus

Cellular and humoral immune responses were studied in squirrel monkeys after primary and challenge infection with a Khartoum strain (WR 378) of Leishmania donovani. Each of 7 squirrel monkeys, Saimiri sciureus, was inoculated intravenously with 5 X 10(7) amastigotes/kg body weight, and one other monkey (control) was inoculated with uninfected hamster spleen homogenate. Five infected monkeys recovered from visceral leishmaniasis and two infected monkeys died. Three of the five squirrel monkeys which recovered from the primary infection demonstrated acquired resistance when challenged with an intravenous inoculation of 1.0 X 10(8) amastigotes of L. donovani/kg of body weight. Each of these same three monkeys, the two remaining monkeys which recovered from the primary infection and an uninfected control monkey, were challenged subsequently with an intradermal injection of 2.2 X 10(7) promastigotes of L. braziliensis panamensis (WR539) and developed cutaneous lesions. The reactivity of peripheral blood leukocytes from infected squirrel monkeys to phytohemagglutinin was depressed 2 to 10 weeks after infection, and the reactivity to concanavalin A was not affected. Data on responses to pokeweed mitogen were inconclusive. Reactivity to leishmanial antigens was detected at 12 weeks after infection, which coincided with a marked decrease or disappearance of parasites in liver imprints. Two of five surviving squirrel monkeys developed weak delayed skin test responses to leishmanin antigens after 23 weeks; the three remaining monkeys were anergic during the primary infection but developed strong delayed skin test responses to leishmanin antigens at 7 weeks after a challenge with L. donovani. All squirrel monkeys inoculated with L. donovani developed a hyperproteinemia, hypergammaglobulinemia, hypoalbuminemia, and a reversal of the albumin/globulin ratio between 4 to 18 weeks after infection. Plasma IgM and IgG levels were increased between 2 to 18 weeks after infection; much of this increase was due to IgG. Class-specific antileishmanial antibodies, with generally low IgM and high IgG titers, reached a maximum after 14 and 16 weeks, respectively. A correlation was observed between concentration of gamma-globulins and plasma IgM and IgG levels, but not gamma-globulin concentrations and maximum titers of class-specific antileishmanial antibodies. Squirrel monkeys challenged with L. donovani again developed hyperproteinemia, hypergammaglobulinemia, and increased concentrations of plasma IgM and IgG which correlated with high titers of IgG class-specific antileishmanial antibody 4 weeks after reinoculation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Laterality in spontaneous motor activity of chimpanzees and squirrel monkeys

Varieties of nonmanipulative motor responses were observed in chimpanzees and squirrel monkeys. Chimpanzees displayed a right hand preference for touching their inanimate environments but used their right and left hands equally for touching their faces and their bodies. The latter result was not consistent with previous reports of a left hand preference for face touching in apes. The right hand preference for environmental touching was stronger in male than in female chimpanzees. Squirrel monkeys had a right preference for combined hand and foot responses directed to their bodies, but expressed no handedness for environmentally directed touching. These limb preferences in chimpanzees and squirrel monkeys indicate that neither precise, complex manipulation nor postural instability are necessary conditions for population level hand preferences. Factor analysis of the chimpanzee manual responses showed distinct self and environmentally directed factors. Analysis of the squirrel monkey data also showed self and environmental factors, except that body scratching had a negative loading on the environmental factor. This latter result suggests that self-scratching by squirrel monkeys is a displacement activity that suppresses manual exploration of the environment. © 1992 Wiley-Liss, Inc.     

Androgen resistance in squirrel monkeys (Saimiri spp.)

The goal of this study was to understand the basis for high androgen levels in squirrel monkeys (Saimiri spp.). Mass spectrometry was used to analyze serum testosterone, androstenedione, and dihydrotestosterone of male squirrel monkeys during the nonbreeding (n = 7) and breeding (n = 10) seasons. All hormone levels were elevated compared with those of humans, even during the nonbreeding season; the highest levels occurred during the breeding season. The ratio of testosterone to dihydrotestosterone in squirrel monkeys is high during the breeding season compared to man. Squirrel monkeys may have high testosterone to compensate for inefficient metabolism to dihydrotestosterone. We also investigated whether squirrel monkeys have high androgens to compensate for low-activity androgen receptors (AR). The response to dihydrotestosterone in squirrel monkey cells transfected with AR and AR-responsive reporter plasmids was 4-fold, compared with 28-fold in human cells. This result was not due to overexpression of cellular FKBP51, which causes glucocorticoid and progestin resistance in squirrel monkeys, because overexpression of FKBP51 had no effect on dihydrotestosterone-stimulated reporter activity in a human fibroblast cell line. To test whether the inherently low levels of FKBP52 in squirrel monkeys contribute to androgen insensitivity, squirrel monkey cells were transfected with an AR expression plasmid, an AR-responsive reporter plasmid, and a plasmid expressing FKBP52. Expression of FKBP52 decreased the EC50 or increased the maximal response to dihydrotestosterone. Therefore, the high androgen levels in squirrel monkeys likely compensate for their relatively low 5 alpha-reductase activity during the breeding season and AR insensitivity resulting from low cellular levels of FKBP52.     

Squirrel monkeys support replication of BK virus more efficiently than simian virus 40: an animal model for human BK virus infection

We performed experiments to test the suitability of squirrel monkeys (Saimiri sciureus) as an experimental model for BK virus (BKV) and simian virus 40 (SV40) infection. Four squirrel monkeys received intravenous inoculation with BKV Gardner strain, and six squirrel monkeys received intravenous inoculation with SV40 777 strain. Eight of 10 monkeys received immunosuppression therapy, namely, cyclophosphamide subcutaneously either before or both before and after viral inoculation. The presence of viral infection was assessed by quantitative real-time PCR amplification of viral DNA from blood, urine, and 10 tissues. We found that squirrel monkeys were susceptible to infection with BKV, with high viral copy number detected in blood and viral genome detected in all tissues examined. BKV genome was detected in urine from only one monkey, while three monkeys manifested focal interstitial nephritis. BKV T antigen was expressed in renal peritubular capillary endothelial cells. By contrast, SV40 was detected at very low copy numbers in only a few tissues and was not detected in blood. We conclude that the squirrel monkey is a suitable animal for studies of experimental BKV infection and may facilitate studies of viral entry, pathogenesis, and therapy.     

Experimental American leishmaniasis in the Brazilian squirrel monkey (Saimiri sciureus): lesions, hematology, cellular, and humoral immune responses

Unulcerated cutaneous lesions appeared and persisted in squirrel monkeys experimentally infected with Leishmania braziliensis braziliensis or L. b. panamensis. Peripheral blood mononuclear cell (PBMC) numbers increased following infection, and cultured PBMCs from infected monkeys proliferated in response to parasite antigens. The responses of PBMCs to mitogens were not suppressed in infected monkeys. Elevated levels of leishmania-specific immunoglobulins M and G were also observed. Thus, the squirrel monkey is susceptible to American leishmaniasis and is capable of responding to the infection with measurable cellular and humoral immunity.     

Pattern of maternal circulating CRH in laboratory‐housed squirrel and owl monkeys

The anthropoid primate placenta appears to be unique in producing corticotropin‐releasing hormone (CRH). Placental CRH is involved in an endocrine circuit key to the production of estrogens during pregnancy. CRH induces cortisol production by the maternal and fetal adrenal glands, leading to further placental CRH production. CRH also stimulates the fetal adrenal glands to produce dehydroepiandrostendione sulfate (DHEAS), which the placenta converts into estrogens. There are at least two patterns of maternal circulating CRH across gestation among anthropoids. Monkeys examined to date (Papio and Callithrix) have an early‐to‐mid gestational peak of circulating CRH, followed by a steady decline to a plateau level, with a possible rise near parturition. In contrast, humans and great apes have an exponential rise in circulating CRH peaking at parturition. To further document and compare patterns of maternal circulating CRH in anthropoid primates, we collected monthly blood samples from 14 squirrel monkeys (Saimiri boliviensis) and ten owl monkeys (Aotus nancymaae) during pregnancy. CRH immunoreactivity was measured from extracted plasma by using solid‐phase radioimmunoassay. Both squirrel and owl monkeys displayed a mid‐gestational peak in circulating CRH: days 45–65 of the 152‐day gestation for squirrel monkeys (mean±SEM CRH=2,694±276 pg/ml) and days 60–80 of the 133‐day gestation for owl monkeys (9,871±974 pg/ml). In squirrel monkeys, circulating CRH declined to 36% of mean peak value by 2 weeks before parturition and then appeared to increase; the best model for circulating CRH over gestation in squirrel monkeys was a cubic function, similar to previous results for baboons and marmosets. In owl monkeys, circulating CRH appeared to reach plateau with no subsequent significant decline approaching parturition, although a cubic function was the best fit. This study provides additional evidence for a mid‐gestational peak of maternal circulating CRH in ancestral anthropoids that has been lost in the hominoid lineage. Am. J. Primatol. 72:1004–1012, 2010. © 2010 Wiley‐Liss, Inc.     

Streptozotocin-induced diabetes mellitus in cynomolgus monkeys: changes in carbohydrate metabolism, skin glycation, and pancreatic islets

Chronic hyperglycemia has been implicated in a number of diabetes mellitus-related conditions in the human population, including retinopathy, neuropathy, nephropathy, and vasculopathy. However, it has been difficult to evaluate the effect of long-term hyperglycemia in a research setting because of the disease's slow progression. In this study, we used streptozotocin (30 mg/kg of body weight, intravenously) to induce a state of chronic hyperglycemia in eight cynomolgus monkeys, and compared these monkeys with a matched control group (n = 8). Seven of eight monkeys with streptozotocin-induced diabetes required insulin therapy to avoid ketosis. After disease induction, all diabetic monkeys had significantly higher preprandial plasma glucose and glycated hemoglobin values, compared with their baseline values or values for control monkeys. Diabetic monkeys also had abnormal responses to an intravenous glucose tolerance test. Consistent with the chronic hyperglycemic state and formation of advanced glycation end products, diabetic monkeys had a significant increase in skin fluorescence over the course of the 6-month study. Plasma triglyceride and cholesterol concentrations increased, but not significantly so, in the diabetic monkeys after disease induction and were not significantly different from concentrations in control monkeys. Six months after disease induction, monkeys were necropsied, and immunohistochemical staining for insulin in the pancreatic islets indicated that diabetic monkeys had a significantly decreased amount of staining for the hormone. The percentage of islet insulin staining was significantly correlated with physiologic responses to the postinduction intravenous glucose tolerance test in all monkeys. Because cynomolgus monkeys are well-characterized models of atherosclerosis, this model may be useful for determining mechanisms whereby diabetes mellitus increases cardiovascular disease.     

Determinants of problem-solving success inSaimiri andCallicebus

The problem-solving behavior of titis and squirrel monkeys was compared on four tasks. Each task was presented at three levels of complexity, based on the number of responses required to obtain a food reward. At all levels, however, food could be obtained by performing a few relatively simple and generalized responses, such as grasping, lifting, or pulling, that were within the repertoire of each species. The principal measures of problem-solving efficiency were the number of trials on which the reward was obtained, and the time required to achieve it. On both measures squirrel monkeys were superior to titis. These differences were not attributable to appetite for food, availability of the requisite instrumental responses, or cognitive ability. The most important factor contributing to the superior achievement of squirrel monkeys was problem-solving “style,” as reflected in latency to approach the problem, tempo of activity, and vigor and variety of responses emitted. On problems where the relevance of these traits was minimal, the level of successful performance was similar in the two species. The importance of taking style into account in comparative assessments of primate problem-solving ability is emphasized by these results.     

Age-related hormonal differences in cycling squirrel monkeys (Saimiri boliviensis boliviensis)

This study was planned to evaluate the poor reproductive performance of aged squirrel monkeys in a self-sustaining breeding colony. Two groups of monkeys aged 6–8 years (Group 1), and >12 years (Group 2) were evaluated. During the midbreeding season, daily blood samples were obtained for a period of 35 days from 10 animals in each group. Blood samples were assayed for serum estradiol (E), progesterone (P), and bioassayable luteinizing hormone (bio-LH) concentrations and the data were analyzed by ANOVA (analysis of variance). Bio-LH surges were less frequent in the aged breeders (Group 2). Total P output during periovulatory period (day ?;3 to day + 3) and the total P output during the luteal phases of the estrus cycles were significantly lower in aged squirrel monkeys (Group 2, P < 0.003). Although E peaks occurred less frequently in Group 2, they had higher concentrations as compared to Group 1 (P < 0.003). Cumulative periovulatory and luteal phase E levels did not differ between the two groups. The reduction in P output in aged squirrel monkeys may interfere with proper implantation, thus contributing to the lower pregnancy rate observed in this age group. The decreased frequency of bio-LH surges indicated less frequent ovulations in the aged animals which may further impair reproduction with aging. © 1994 Wiley-Liss, Inc.     

Effects of 17-hydroxyprogesterone caproate (17-OHPC) administration to pregnant squirrel monkeys (Saimiri boliviensis boliviensis)

Poor reproductive performance of the squirrel monkey (Saimiri boliviensis boliviensis) in captivity and a relative progesterone (P) deficiency in pregnancy have been reported. Since premature births may contribute to pregnancy wastage, we attempted to measure the effectiveness of 17-hydroxyprogesterone caproate (17-OHPC) treatment of pregnant squirrel monkeys to prevent early deliveries. Based on clearance studies of nonpregnant animals, 25 mg of 17-OHPC was administered at 6-day intervals to a test group of 31 pregnant monkeys while the control group of 29 received saline. Venous blood was obtained at 6- to 12-day intervals for measurement of 17-hydroxyprogesterone (17-OHP), P, 17-B estradiol (E), and androstenedione (A), and dihydroepiandrosterone (DHEA) levels by radioimmunoassays. The treated group had a significant increase in serum 17-OHP (P < 0.001), P (P < 0.01), and DHEA (P < 0.05) levels compared to controls. The numbers of live births, stillbirths, or neonatal deaths did not differ significantly between groups. Although 17-OHPC administration appeared to increase P and 17-OHP levels, this did not alter the duration of pregnancy nor delay the onset of labor. A significant fall in 17-OHP, P, and E levels was observed 6–12 days before delivery.     

Predation by squirrel monkeys and double-toothed kites on tent-making bats

Central American squirrel monkeys (Saimiri oerstedi) appear to recognize the modified leaves that phyllostomid bats utilize for diurnal roost sites. The monkeys visually and manually search these bat tents for both bats and insects. Adult males are the most successful at capturing bats. Nonvolant juvenile bats are more vulnerable to monkey predation than are adults. Bats that escape monkey predation frequently are captured by doubletoothed kites (Harpagus bidentatus) that tend foraging troops of monkeys. Predation by squirrel monkeys, coupled with that of double-toothed kites, may be a significant source of mortality for tent-making bats.     

Haptic discrimination of size and texture in squirrel monkeys (Saimiri sciureus)

The present study analyzed haptic abilities of four squirrel monkeys. Using a two-alternative forced-choice procedure, stimuli were presented in a visually opaque box, allowing unrestrained test subjects to grab through a small opening and touch the discriminanda. Difference thresholds were determined by a modified method of limits. In the first experiment we determined size difference thresholds for the discrimination of circular cylinders using standard stimuli differing in diameter from 10 mm to 35 mm. In the second experiment a texture difference threshold was obtained for the discrimination of grooved surfaces (groove width 2-7 mm). The squirrel monkeys achieved a mean size difference threshold of 8% stimulus difference. The linear increase of absolute thresholds as a function of the starting stimulus size showed that haptic size discriminations in squirrel monkeys correspond to Weber's law. Three of the animals achieved a texture difference of 10% stimulus difference, while one monkey showed a distinctively lower haptic acuity. An analysis of the exploratory behavior points to a subject-related difference in the significance of cutaneous and kinesthetic information during size discriminations. Whereas differences in the animals' exploratory behavior did not correlate with the size difference threshold a subject achieved, different thresholds for texture discrimination can be explained by the different exploratory procedures the monkeys used to touch grooved surfaces. The low difference thresholds determined for the squirrel monkeys in the present study point to the significance of unrestrained test conditions for the assessment of the haptic capacity of a species.     

Validated liquid chromatographic-electrospray ionization mass spectrometric assay for simultaneous determination of 3,4-methylenedioxymethamphetamine and its metabolites 3,4-methylenedioxyamphetamine, 3,4-dihydroxymethamphetamine, and 4-hydroxy-3-methoxymethamphetamine in squirrel monkey plasma

3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug with neurotoxic potential. Pharmacokinetic data of MDMA and its metabolites may shed light on the mechanism of MDMA neurotoxicity. An LC-MS assay with electrospray ionization (ESI) is presented for quantifying MDMA and its metabolites 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymethamphetamine (HHMA), and 4-hydroxy-3-methoxymethamphetamine (HMMA) in squirrel monkey plasma. The method involved enzymatic conjugate cleavage and protein precipitation. Separation was achieved within 14min. The method was validated according to international guidelines with respect to selectivity, linearity, accuracy, precision, recovery, and matrix effect. The present method should prove useful for acquiring pharmacokinetic and toxicokinetic data in squirrel monkeys.     

Haptic discrimination of size and texture in squirrel monkeys ( Saimiri sciureus )

The present study analyzed haptic abilities of four squirrel monkeys. Using a two-alternative forced-choice procedure, stimuli were presented in a visually opaque box, allowing unrestrained test subjects to grab through a small opening and touch the discriminanda. Difference thresholds were determined by a modified method of limits. In the first experiment we determined size difference thresholds for the discrimination of circular cylinders using standard stimuli differing in diameter from 10 mm to 35 mm. In the second experiment a texture difference threshold was obtained for the discrimination of grooved surfaces (groove width 2-7 mm).The squirrel monkeys achieved a mean size difference threshold of 8% stimulus difference. The linear increase of absolute thresholds as a function of the starting stimulus size showed that haptic size discriminations in squirrel monkeys correspond to Weber's law. Three of the animals achieved a texture difference of 10% stimulus difference, while one monkey showed a distinctively lower haptic acuity. An analysis of the exploratory behavior points to a subject-related difference in the significance of cutaneous and kinesthetic information during size discriminations. Whereas differences in the animals' exploratory behavior did not correlate with the size difference threshold a subject achieved, different thresholds for texture discrimination can be explained by the different exploratory procedures the monkeys used to touch grooved surfaces. The low difference thresholds determined for the squirrel monkeys in the present study point to the significance of unrestrained test conditions for the assessment of the haptic capacity of a species.     

Sleep quantitation in common marmoset, cotton top tamarin and squirrel monkey by non-invasive actigraphy

Sleep quantitation data on the Neotropical primate species, apart from the squirrel monkey, are still sparse. As such, we have quantitated sleep in the common marmosets (Callithrix jacchus), cotton top tamarins (Saguinus oedipus) and squirrel monkeys (Saimiri sciureus) reared in one primate facility simultaneously, by non-invasive actigraphy. The range in total sleep time/24h measured for male adult common marmosets, cotton top tamarins and squirrel monkeys were 713-793 min (n=4), 707-889 min (n=4) and 459-475 min (n=2) respectively. The range in sleep episode length /12h dark phase for marmosets, tamarins and squirrel monkeys were 21-52 min (n=3), 10-28 min (n=4) and 9-15 min (n=2) respectively. Since vigilance is a critical evolutionary adaptive feature of predator avoidance among Callitrichid monkeys and squirrel monkeys, the shorter ranges in sleep episode length recorded, even under captivity, in this study could be interpreted as probable indicators of such vigilance behavior during the rest phase. We hypothesize that the vigilance behavior when it exists during a primate's active phase should also prevail when it is at rest (sleep). This hypothesis deserves additional testing in female Callitrichid monkeys.     

An immunoradiometric assay for squirrel monkey prolactin.

Determination of immunoreactive prolactin in squirrel monkeys has been hampered by the lack of specific antibodies. We investigated the adaptability of a commercially available immunoradiometric assay for human prolactin, which employs two separate monoclonal antibodies (MAb I and II) to human prolactin, to determine the presence of squirrel monkey prolactin. We found that immunoreactivity curves for prolactin in squirrel monkey pituitary homogenates and serum were parallel to human prolactin standards, suggesting that the epitopes recognized by these antibodies were common to both human and squirrel monkey prolactin. Both nonglycosylated (23 kD) and glycosylated (26 kD) forms of squirrel monkey prolactin were detected in squirrel monkey pituitary homogenates by Western blot analysis using [125I]-MAb II. Neither sheep nor rat prolactin was recognized by Western blot analysis, indicating that the assay may be specific for primate prolactins. We examined the effect of ketamine HCl, an anesthetic that has been shown to elevate serum prolactin levels in other primates, on prolactin secretion in squirrel monkeys. Serum prolactin levels increased greater than fourfold after the administration of ketamine HCl (30 mg/kg b.w., i.m.) compared with control levels. Serum prolactin levels were unaffected by anesthesia with pentobarbital sodium (15 mg/kg b.w., i.v.). This assay provides a reliable and sensitive method for determining immunoreactive squirrel monkey prolactin.     

Squirrel monkeys' response to inequitable outcomes indicates a behavioural convergence within the primates

Although several primates respond negatively to inequity, it is unknown whether this results from homology or convergent processes. Behaviours shared within a taxonomic group are often assumed to be homologous, yet this distinction is important for a better understanding of the function of the behaviour. Previous hypotheses have linked cooperation and inequity responses. Supporting this, all species in which inequity responses have been documented are cooperative. In this study, we tested this hypothesis by investigating the response to inequity in squirrel monkeys, which share a phylogenetic family with capuchin monkeys, but do not cooperate extensively. Subjects exchanged tokens to receive food rewards in conditions in which the level of effort required and reward received varied. Squirrel monkeys did not respond negatively to inequity. However, the monkeys were sensitive to the variation present in the task; male subjects showed a contrast effect and, as in previous studies, subjects were more sensitive to differences in reward in the context of a task than when rewards were given for free. Taken with other results, these results support the hypothesis that a negative response to inequity evolved convergently in primates, probably as a mechanism for evaluating outcomes relative to one's partners in cooperative species.     

Insect-catching behavior in socially inexperienced infant squirrel monkeys

Insects are an essential component of squirrel monkey natural food. Eight of ten socially inexperienced infant squirrel monkeys, during their 2nd and 3rd month of age, directed their attention to living insects or film presentations of moving insects. They attempted to catch them with gradually improving success, and on at least two occasions consumed them. For comparison, group-living squirrel monkeys begin to eat solid food around their 2nd month of age, continuing with some nursing until about 11 or 13 months, and were only at this age seen to successfully catch and eat insects. Thus, as infant squirrel monkeys proved to be able to catch and eat insects before their first experience with conspecifics, an innate basis for this behavior can be assumed.