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PubMed2005

Mossy cells and different subpopulations of pyramidal neurons are immunoreactive for cocaine- and amphetamine-regulated transcript peptide in the hippocampal formation of non-human primates and tree shrew (Tupaia belangeri).

Cocaine- and amphetamine-regulated transcript peptide mRNA was discovered in the rat striatum following cocaine and amphetamine administration. Since both psychostimulants elicit memory-related effects, localization of cocaine- and amphetamine-regulated transcript peptide in the hippocampal formation may have functional importance. Previous studies demonstrated different cellular localizations of cocaine- and amphetamine-regulated transcript peptide in humans and in rodents. Mossy cells were cocaine- and amphetamine-regulated transcript-positive in the human dentate gyrus, whereas granule cells contained this peptide in the rat. In the present study, the localization of cocaine- and amphetamine-regulated transcript peptide was examined using immunohistochemistry in the hippocampal formation of the rhesus monkey (Macaca mulatta), the common marmoset monkey (Callithrix jacchus) and in the tree shrew (Tupaia belangeri). In these species principal neurons of the hippocampal formation were cocaine- and amphetamine-regulated transcript-immunoreactive. In both monkeys and tree shrews, mossy cells of the hilus were cocaine- and amphetamine-regulated transcript-positive whereas granule cells of the dentate gyrus were cocaine- and amphetamine-regulated transcript-negative. The dense cocaine- and amphetamine-regulated transcript-immunoreactive axonal plexus of the associational pathway outlined the inner one-third of the dentate molecular layer. In the hippocampus of the tree shrew and marmoset monkey, a subset of CA3 pyramidal cells were cocaine- and amphetamine-regulated transcript-immunoreactive. In the marmoset monkey, cocaine- and amphetamine-regulated transcript labeling was found only in layer V pyramidal cells of the entorhinal cortex, while in the rhesus monkey, pyramidal cells of layers II and III were cocaine- and amphetamine-regulated transcript-immunopositive. Our results show that cocaine- and amphetamine-regulated transcript positive neurons in the dentate gyrus of non-human primates are similar to that of the human. Furthermore, in the hippocampal formation of the tree shrew similar cocaine- and amphetamine-regulated transcript-immunoreactive cell-types were observed as in monkeys, supporting their evolutionary relationship with primates. Mossy cells and granule cells are members of a mutual excitatory intrahippocampal circuitry, therefore cocaine- and amphetamine-regulated transcript-immunoreactivity of these neurons in primates and rodents suggests that psychostimulants cocaine and amphetamine may induce memory-related effects at different points of the same excitatory circuitry in the hippocampal formation.

Animals↗
PubMed2004

Intensity of aggressive interactions modulates testosterone in male marmosets.

Androgen is associated with the expression of male-typical behavior, including aggressive behavior, but high levels of androgen may be incompatible with other behavioral systems, such as paternal care. In a variety of species of birds that display paternal care, testosterone (T) levels in males are maintained at low levels, and these levels rise only in response to direct agonistic challenges. This idea has not been thoroughly studied in mammals with biparental care, and we exposed male marmosets (Callithrix kuhlii), a monogamous and biparental primate to aggressive interactions with unfamiliar intruders. Urinary levels of T and cortisol (CORT) were monitored prior to and following these interactions. Baseline T was not correlated with variation in aggression in either residents or intruders, and CORT was not affected by the encounters. However, males responded to an encounter with male intruders with changes in T that correlated with the level of aggression displayed by the resident male during the trial. Encounters with male intruders that elicited high frequencies of aggressive displays by the male resident were associated with increased T 2-6 h and 24 h following the encounter, and encounters that had few aggressive displays resulted in no change or a decrease in T concentrations. Intruders did not demonstrate a significant relationship between T and aggression. Thus, the magnitude of the hormonal response is dependent on the intensity of aggression during a male-male encounter, suggesting that elevated androgens are likely to be a consequence, rather than a cause, of aggressive interactions in marmosets.

Age Factors↗
PubMed2005

Flow cytometric sorting of non-human primate sperm nuclei.

Pre-determination of the sex of offspring has implications for management and conservation of captive wildlife species, particularly those with single sex-dominated social structures. Our goal is to adapt flow cytometry technology to sort spermatozoa of non-human primate species for use with assisted reproductive technologies. The objectives of this study were to: (i) determine the difference in DNA content between X- and Y-bearing spermatozoa (ii) sort sperm nuclei into X- and Y-enriched samples; and (iii) assess the accuracy of sorting. Spermatozoa were collected from two common marmosets (Callithrix jacchus), seven hamadryas baboons (Papio hamadryas) and two common chimpanzees (Pan troglodytes). Human spermatozoa from one male were used as a control. Sperm nuclei were stained (Hoechst 33342), incubated and analyzed using a high-speed cell sorter. Flow cytometric reanalysis of sorted samples (sort reanalysis, 10,000 events/sample) and fluorescence in situ hybridization (FISH; 500 sperm nuclei/sample) were used to evaluate accuracy of sorting. Based on fluorescence intensity of X- and Y-bearing sperm nuclei, the difference in DNA content between X and Y populations was 4.09 +/- 0.03, 4.20 +/- 0.03, 3.30 +/- 0.01, and 2.97 +/- 0.05%, for marmoset, baboon, chimpanzee and human, respectively. Sort reanalysis and FISH results were similar; combined data revealed high levels of purity for X- and Y-enriched samples (94 +/- 0.9 and 93 +/- 0.8%, 94 +/- 0.7 and 94 +/- 0.5%, 91 +/- 0.9 and 97 +/- 0.6%, 94 +/- 0.6 and 94 +/- 0.9%, for marmoset, baboon, chimpanzee and human, respectively). These data indicate the potential for high-purity sorting of spermatozoa from non-human primates.

Animals↗
PubMed2005

Differential signatures of protein expression in marmoset liver and thymus induced by single-dose TCDD treatment.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an ubiquitously distributed environmental pollutant. Health effects have been studied intensively, but low-dose effects are quite complex and not yet fully understood. In many studies, the immune system was identified as the most sensitive target. Here, we demonstrate changes of protein expression in liver and thymus of male marmosets (Callithrix jacchus) which were subjected to a single dose of a subcutaneous injection of 100 ng/kg body weight TCDD. Histopathological examination revealed myocardial fibrosis, but there were no significant findings in pathology and histopathology of liver and thymus. In order to detect more subtle treatment-related changes, we performed a comparative proteomic investigation of liver and thymus using a 2-D gel electrophoresis based proteomics approach. Fluorescence labeling and automated image analysis was used to enhance sensitivity and reproducibility. In both organs, distinct changes of protein expression were detected which were more pronounced in thymus, where the pattern of deregulated proteins could be clearly related to immune responses. In the thymus of treated animals, several toxicologically relevant factors were increased, including chaperones, glycerol-3-phosphate dehydrogenase, and adseverin. Among others, vimentin, Ca-dependent protease and protein disulfide isomerase were downregulated. In the liver, transferrins, lamin A and HSP70 were upregulated, whereas thymidine phosphorylase (synonyms: endothelial cell growth factor, PD-ECGF, gliostatin) was significantly reduced. Comparative analysis of deregulated proteins in both organs revealed a pattern of related functions, which fits well into the existing knowledge of the toxic processes and mechanisms underlying TCDD-mediated toxicity.

Animals↗
PubMed2005

Acute GB virus B infection of marmosets is accompanied by mutations in the NS5A protein.

GBV-B, a member of the Flaviviridae family of viruses, is the virus most closely related to HCV, and GBV-B infection in tamarin monkeys might represent a valuable surrogate animal model of HCV infection. In the current study, GBV-B was successfully transmitted to two marmosets (Callithrix jaccus). The infection resulted in viremia of 14- and 17-week duration, respectively, and was accompanied by elevation of isocitrate dehydrogenase activity. These data confirm that marmosets might represent an attractive model for GBV-B infection. The sequence of GBV-B NS5A, which was previously reported to have one of the highest mutation rates during infection in tamarins, was determined for viruses recovered from the inoculum and from marmoset blood samples obtained at weeks 1, 8, and 14 post inoculation in one marmoset and at weeks 2, 8, and 17 post inoculation in the other marmoset. In both animals, we detected four substitutions (R1945K, K2052G, F2196L, and G2268E), in the virus recovered immediately before viral clearance. Interestingly, two of these mutations (F2196L and G2268E) were described recently for viruses recovered from persistently infected tamarins. Appearance of these mutations presumably reflects a mechanism of immune escape rather than adaptation of the virus to a new host.

Acute Disease↗
PubMed2006

Social suppression of cortisol in female marmosets: role of luteinizing hormone/chorionic gonadotropin.

Behaviorally subordinate female common marmosets (Callithrix jacchus) undergo suppression of ovulation and chronic reductions in basal plasma cortisol concentrations. Indirect evidence suggests that hypophyseal chorionic gonadotropin (CG; the major pituitary luteinizing gonadotropin in marmosets) may elevate cortisol concentrations in female marmosets, and therefore that social suppression of CG may contribute to diminution of cortisol in subordinates. To test this hypothesis, we determined whether pharmacological inhibition of pituitary CG release decreases basal and adrenocorticotropin (ACTH)-stimulated cortisol secretion. We characterized cortisol and reproductive hormone concentrations in six ovary-intact and six ovariectomized marmosets during long-term treatment with leuprolide acetate, a gonadotropin-releasing hormone (GnRH) agonist, and vehicle. Leuprolide suppressed basal plasma CG concentrations, abolished the CG response to exogenous GnRH, and, in intact animals, blocked ovarian cyclicity. During treatment with vehicle, plasma cortisol concentrations were elevated during the periovulatory phase in intact females, compared to the follicular phase, the luteal phase, and ovariectomized females. Leuprolide suppressed basal cortisol concentrations of intact females as compared to the periovulatory phase, but did not affect basal cortisol in ovariectomized animals and did not alter responses to exogenous ACTH. These findings suggest that elevations in circulating CG concentrations are associated with elevated cortisol concentrations in female marmosets, and that this relationship requires simultaneous increases in ovarian hormones that occur only during the periovulatory period. Thus, suppression of CG release in anovulatory subordinate females may not play an important role in socially induced diminution of cortisol.

Adrenocorticotropic Hormone↗
PubMed2005

Elevated urinary testosterone excretion and decreased maternal caregiving effort in marmosets when conception occurs during the period of infant dependence.

The proximate mechanisms that regulate transitions in mammalian female reproductive effort have not been widely studied. However, variation in circulating levels of the androgenic steroid hormone testosterone (T) appears to mediate a trade-off between investment in current and future offspring in males [Ketterson, E.D., Nolan, V., Jr., 1992. Hormones and life histories: an integrative approach. Am. Nat. 140, S33-S62; Ketterson, E.D., Nolan, V., Jr., 1994. Hormones and life histories: an integrative approach. In: L.A. Real (Ed.), Behavioral Mechanisms in Evolutionary Ecology, University of Chicago Press, Chicago, pp. 327-353; Ketterson, E. D., Nolan, V., Jr., 1999. Adaptation, exaptation, and constraint: A hormonal perspective. Am. Nat. 154S, S4-S25]. The purpose of this study was to investigate the possibility that T is also associated with transitions in the reproductive effort of females, by examining the relationship between urinary T excretion, maternal caregiving behavior, and the timing of the postpartum conception in female Wied's black tufted-ear marmosets (Callithrix kuhlii). We examined the maternal carrying effort and peripartum T profiles of six females across two conditions: (1) when they conceived during the period of infant dependence (DPID), such that gestation was coupled with lactation; and (2) when the same females conceived after the period of infant dependence (APID). We also assessed the relationship between postpartum T levels and caregiving effort. When female marmosets conceived DPID, they dramatically reduced their caregiving effort, and had higher levels of urinary T, relative to when they conceived APID. Further, the litter-to-litter changes in maternal caregiving effort that we observed were related to variation in urinary T excretion; as weekly levels of urinary T excretion increased, concurrent caregiving effort declined. Our results suggest that variation in T secretion may regulate transitions in female reproductive behavior, and that the regulation of male and female parental behavior may be mediated by homologous neuroendocrine mechanisms.

Animals↗
PubMed2004

Diminished maternal responsiveness during pregnancy in multiparous female common marmosets.

Common marmoset monkeys (Callithrix jacchus) live in small groups in which, usually, only a single female breeds and all group members provide infant care. When two females breed concurrently, however, they may commonly kill one another's infants, especially during the peripartum period. To investigate the mechanisms underlying infanticide by breeding females, we characterized responses of multiparous females to infants and determined circulating hormone levels in adult females during early pregnancy, late pregnancy, and the early postpartum period. Additionally, we compared the responses of postpartum females to their own infants and infants of other females (unfamiliar infants). Postpartum females were highly maternal toward both their own and unfamiliar infants, and showed no differences in their behavioral or hormonal responses to the two. During both early and late pregnancy, however, these females exhibited longer latencies to initially approach unfamiliar infants and spent less time carrying unfamiliar infants. Moreover, females spent less time carrying unfamiliar infants during late pregnancy than early pregnancy. Most late pregnant females never carried infants, and those that did rejected them quickly. Prolactin concentrations were higher and progesterone concentrations lower postpartum than in early or late pregnancy, while estradiol concentrations, the estradiol-to-progesterone ratio, and cortisol levels were higher during late pregnancy. Within reproductive conditions, however, maternal behaviors were not correlated with hormone levels. These results suggest that maternal responsiveness in marmosets may be attenuated during pregnancy, especially late pregnancy, and this may contribute to infanticide by breeding females.

Aggression↗
PubMed2005

Mobbing vocalizations as a coping response in the common marmoset.

Using a non-invasive method of sampling saliva followed by assay for cortisol levels, we found that common marmosets (Callithrix jacchus) show a decrease in cortisol levels after seeing a snake-model stimulus that reliably elicits mobbing (tsik) calls. In fact, there was a significant positive correlation between the number of tsik vocalizations made and the magnitude of the decrease in the cortisol concentrations. Furthermore, marmosets with higher levels of cortisol prior to being exposed to the stimulus produce more tsik calls than those with lower levels of cortisol. Subsequent experiments showed that, in response to 15 min of isolation with no visual or auditory contact with conspecifics (a traditional stressor), cortisol levels increased significantly. However, playback of the mobbing calls of a familiar conspecific to individual isolated marmosets not only prevented the rise in cortisol, but also actually caused a decrease in the levels of this hormone. This suggests that the mobbing calls serve to calm the marmoset after experiencing a stressful situation. This finding results in a greater understanding as to the role of physiological responses during communication in this species and could have implications for the welfare of marmosets in captivity.

Adaptation, Psychological↗
PubMed2001

Visual discrimination learning impairments produced by combined transections of the anterior temporal stem, amygdala and fornix in marmoset monkeys.

Marmoset monkeys (Callithrix jacchus) with bilateral transections of the anterior temporal stem, amygdala and fornix were unable to relearn a 2-choice object discrimination first learnt prior to surgery, and were very severely impaired at relearning a concurrent object discrimination task which they had learnt and relearnt prior to surgery, indicating that they had a dense retrograde amnesia. They also had difficulty learning new visual object discriminations but were only mildly impaired on spatial learning. When tested on new learning of concurrent discriminations 8 to 10 weeks after surgery, three operated monkeys were unable to reach criterion in 400 trials while the remaining two operated monkeys performed within the normal range. The operated monkeys were subsequently shown to be impaired on acquisition of shape discriminations using black objects. These anterograde effects suggest that the impairment runs mainly in the domain of visual analysis. The monkeys also exhibited many of the features of the Klüver-Bucy syndrome. Histological analysis indicated that in addition to cutting some of the subcortical temporal lobe efferent pathways, the surgical procedures had cut the cholinergic afferents to the temporal neocortex, entorhinal cortex, and hippocampus. In a second experiment we found that treatment with the cholinergic agonist pilocarpine, which is effective in monkeys with specific cholinergic lesions, was unable to remediate the lesion-induced impairments. This suggests that transection of the non-cholinergic afferents, or the temporal lobe subcortical efferents, contributed to the behavioural syndrome and the learning and retention deficits seen in these monkeys.

Acetylcholinesterase↗
PubMed2002

Acute and repeated treatment with L-DOPA increase c-jun expression in the 6-hydroxydopamine-lesioned forebrain of rats and common marmosets.

L-DOPA was acutely or repeatedly administered to rats and common marmosets (Callithrix jacchus) with unilateral 6-hydroxydopamine (6-OHDA) denervation of the dopamine inputs to the forebrain. Using in situ hybridization it was found that L-DOPA-treated animals exhibited a pronounced induction in the gene expression of both c-jun and c-fos in striatum and cerebral cortex restricted to the dopamine-depleted hemisphere. In contrast, acute treatment with cocaine induced c-fos mRNA, but not c-jun mRNA, in the striatum of normal animals. These data suggest that dopamine denervation leads to neurochemical adaptations which enables L-DOPA to induce a sustained gene expression of c-jun. Such aberrant gene regulation may underlie the development of L-DOPA-induced movement disorders which are commonly found in patients with Parkinson's disease.

Animals↗
PubMed1986

Postnatal development of quantitative morphological parameters in the lateral geniculate nucleus of the marmoset monkey.

Quantitative morphological parameters were studied in the lateral geniculate nucleus (LGN) of the marmoset monkey (Callithrix jacchus) during development, using a series of 14 animals, at ages from birth to adulthood. They include the volume of the LGN and of its layers and interlaminar zones, their neuronal content expressed as numerical density and total number, and the density and number of glial cells in the nucleus as a whole. The volume of the LGN increases rapidly after birth, reaches a maximum at 6 months of age, and then decreases to its adult value of about 11 mm3. Neuronal density follows a reciprocal curve, reaching an adult value of about 41,000 neurons/mm3, so that the total number of about 440,000 neurons per LGN remains constant throughout life although large interindividual variations, especially in juveniles, do not allow unequivocal statements about total neuronal number to be made. Parvocellular layers occupy most of the geniculate volume, and contain about 74% of its neurons in the adult. We found no difference in their development pattern compared with the magnocellular component. The 'superficial' layers and interlaminar zones contain more than 15% of the geniculate neurons, and they could therefore play an important functional role in the primary visual pathway of New World primates. The number of glial cells nearly triples during the first 6 weeks and stabilizes around 800,000 in the LGN of one hemisphere. As the same brains were used as in a previous study on the area 17 of the marmoset (Dev. Brain Res., 29 (1986) 173-188) direct comparisons of the development of cortex and thalamus can be made. Their development is parallel in time, and in both cases the adult values for volume, neuronal density and glial numbers are reached several months postnatally.

Animals↗
PubMed1996

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in non-human primates is antagonized by pretreatment with nimodipine at the nigral, but not at the striatal level.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism in man and non-human primates. Hypotheses concerning the mechanism of action of MPTP have been related to the pathogenesis of nigral cell death in Parkinson's disease. For instance, alterations of calcium influxes have been reported to be implicated in both MPTP-induced parkinsonism and Parkinson's disease. Recently, we reported that nimodipine, a blocker of L-type calcium channels, prevents dopaminergic MPTP-induced neurotoxicity in C57B1/6 black mice. The present study extended these rodent findings to the non-human primate model of Parkinson's disease and assessed the effects of nimodipine, continuously applied by pellet for 18 days, on behavioural, biochemical and histological parameters, following systemic application of MPTP in common marmosets (Callithrix jacchus). The experimental design involved five groups of common marmosets and a total of 24 animals. Monkeys assigned to group I (n = 4) received subcutaneously implanted vehicle pellets 7 days prior to subcutaneous saline injections (control). Monkeys of group II (n = 4) were treated with nimodipine pellets (80 mg) and saline injections. Marmosets in group III (n = 8) were treated with vehicle pellets and received 4 times MPTP (MPTP-HCl, 2 mg/kg body weight subcutaneously, separated by an interval of 24 h for a total of 4 days). Monkeys in group IV (n = 4) and V (n = 4) were treated as group-III animals except for the implantation of nimodipine pellets (80 mg and 120 mg, respectively) 7 days prior to toxin exposure. In common marmosets MPTP induced severe parkinsonian symptoms, a pronounced dopamine depletion in the caudate-putamen (more than 99% of control) and a loss of tyrosine hydroxylase immunoreactive cells in the substantia nigra (50% percent of control) 7 days after MPTP-administration. Pretreatment with nimodipine (120 mg pellets) did neither attenuate the behavioural impairments in MPTP-treated animals nor antagonize the striatal neurotoxin-induced dopamine depletion, but almost completely prevented (in a dose-dependent manner) the MPTP-induced decrease of nigral tyrosine hydroxylase immunoreactive cells. These data suggest that application of nimodipine, during the observation period of 7 days, protects against MPTP-induced neurotoxicity in common marmosets at the cellular nigral level, but not at the synaptic striatal level, implicating differential mechanisms of actions of MPTP-induced neurotoxicity at the nigral versus the striatal level.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Is there a geniculohypothalamic tract in primates? A comparative immunohistochemical study in the circadian system of strepsirhine and haplorhine species.

In rodents, the circadian rhythm generated by the hypothalamic suprachiasmatic nucleus (SCN) is modulated by two types of phenomena: photic phase-shifts, mediated by the retinohypothalamic pathway and non-photic phase-shifts mediated by the projection of the intergeniculate leaflet (IGL) to the SCN which contains the neuropeptide Y (NPY). In primates, the retinohypothalamic pathway has been well-demonstrated but very little is known about the geniculohypothalamic tract. This prompted us to study NPY immunoreactivity in both the SCN and the IGL in species representative of the three main primate lineages: prosimians (Microcebus), New World monkeys (Callithrix) and Old World monkeys (Macacca). In species studied, we found a region in the pregeniculate nucleus containing both NPY immunopositive cells and substance P immunopositive fibres that we identified as the IGL. During evolution, this structure has moved from a ventral to a dorsomedial position relative to the adjacent dorsal lateral geniculate nucleus. By contrast, NPY-IP fibres in the SCN are dense in prosimians, but are sparse or absent in other primate species. We suggest that either the geniculohypothalamic projection is absent in higher primates as is the case in humans, or is absent in diurnal mammals, or contains a different peptide, or that NPY immunoreactivity varies according to other parameters.

Animals↗
PubMed2000

Motor effects of (-)-OSU6162 in primates with unilateral 6-hydroxydopamine lesions.

The effects of the novel compound, (-)-OSU6162 ((S)-(-)-3-methylsulfonylphenyl-1-propylpiperidine), on rotational behavior induced by dopamine receptor agonists was investigated in common marmosets (Callithrix jacchus) with unilateral 6-hydroxydopamine lesions. (-)-OSU6162 per se displayed no effect on the animals' behavior. On the other hand, pretreatment with (-)-OSU6162 attenuated rotational behavior induced by apomorphine (apomorphini hydrochloridum), L-DOPA (3,4-dihydroxyphenylalanine), and the dopamine D2 receptor agonist, quinpirole (trans-(-)-4aR-4,4a, 5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolol[3,4-g]quinoline hydrochloride), without inducing motor impairment such as akinesia or dystonia. In addition, treatment with (-)-OSU6162 for 5 consecutive days almost completely abolished the rotational behavior provoked by apomorphine and produced a transient subsensitization of such apomorphine-induced effects after it was discontinued. Moreover, pretreatment with (-)-OSU6162 in two monkeys augmented the rotational behavior elicited by the dopamine D1 receptor agonists, SKF-81297 (R(+)-6-chloro-7,8,dihydroxy-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine hydrobromide) and A-77636 ((-)-(1R, 3S)-3-adamantyl-1-(aminomethyl)-3,4-dihydro-5, 6-dihydroxy-1H-2-benzopyran hydrochloride). The findings indicate that (-)-OSU6162 can exert indirect state-dependent effects that differentially affect dopamine D1 and dopamine D2 receptor agonist-induced behavior.

Adamantane↗
PubMed2003

Sensorimotor deficits in a unilateral intrastriatal 6-OHDA partial lesion model of Parkinson's disease in marmoset monkeys.

Animal studies investigating the efficacy of neurotrophic factors as treatments for Parkinson's disease (PD) ideally require partial dopamine (DA) lesion models. The intrastriatal 6-hydroxydopamine (6-OHDA) lesion model may be suitable for this purpose. Although this model has been well characterized in rodents, it has not previously been used in monkeys. The goal of the present study was to characterize the behavioral effects of unilateral injections of 6-OHDA in the basal ganglia of common marmoset monkeys (Callithrix jacchus). Cell counts from tyrosine hydroxylase immunochemistry 5 months postlesion revealed DA cell loss in the substantia nigra on the lesioned side to approximately 46% of relative to the unlesioned side. 6-OHDA lesioned monkeys showed a variety of behavioral deficits. Apomorphine induced rotation and simple sensorimotor measures (head position bias and PD disability rating score) were most affected by the lesion. The largest deficits were seen at 1 or 2 weeks postsurgery but had recovered by week 10. 6-OHDA lesioned monkeys took longer to complete a more complex sensorimotor staircase task. At 3.5 months postlesion, 6-OHDA monkeys also showed deficits on an object retrieval task designed to measure sensorimotor planning and skilled hand use. alpha-Methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, reinstated those deficits which had undergone recovery in the lesioned animals and also exacerbated the deficits on the staircase task. This model has potential in assessing treatments for PD aimed at curtailing disease progression such as continuous delivery of neurotrophic factors.

Animals↗
PubMed1985

Colonic mucin composition in primates. Selective alterations associated with spontaneous colitis in the cotton-top tamarin.

Heterogeneity of colonic mucin glycoprotein was examined in rectal mucosal biopsy specimens from a variety of primate species (Saguinus oedipus, n = 18; Macaca mulatta, n = 2; Macaca fascicularis, n = 2; Aotus trivirgatus, n = 2; Saimiri sciureus, n = 2; and Callithrix jacchus, n = 2). After initial separation of radiolabeled mucin and nonmucin glycoproteins solubilized from mucosal biopsy specimens, at least five labeled mucin components were found in monkey rectal mucosa in contrast to the six mucin fractions observed in the human colon. Although primates consistently lacked the earliest eluting component present in human colonic mucin, other mucin components cochromatographed with comparable fractions previously identified in human colonic biopsy specimens. The relative proportions of each fraction were consistent throughout all species except the cotton-top tamarin (S. oedipus), an animal that develops a chronic colitis. The cotton-top tamarin was found to have a markedly reduced amount of one mucin component (IV) in a manner analogous to the reduction in a human mucin fraction previously noted in patients with ulcerative colitis. Sequential evaluation of mucin profiles in cotton-top tamarins (n = 12) treated with sulfasalazine (50 mg/kg X day) or placebo in a 10-wk double-blind crossover study demonstrated the persistence of the selective reduction in tamarin species IV unrelated to disease activity. In contrast, the relative amount of tamarin mucin III was greater in association with increased disease activity than that observed in association with reduced disease activity (46% +/- 11% total mucin vs. 19% +/- 7% total mucin posttreatment).

Animals↗
PubMed2002

Characterization of urinary and fecal metabolites of testosterone and their measurement for assessing gonadal endocrine function in male nonhuman primates.

The aims of the present study were (i) to provide basic comparative data on the time course, route, and characteristics of excreted [14C]testosterone (T) metabolites in three nonhuman primates: the common marmoset (Callithrix jacchus), the long-tailed macaque (Macaca fascicularis) and the chimpanzee (Pan troglodytes) and (ii) to use this information to help validate the measurement of urinary and fecal testosterone metabolites for assessing androgen status in Anthropoid primates. Radiolabeled 14C-T (10-30 microCi) was injected intravenously into one adult male of each species and the excreta collected over the next 5 days. Peak radioactivity in urine was detected within 2h and accounted for 67% (Mf), 80% (Cj) and 91% (Pt) of the total radioactivity recovered. The time course of excretion of radioactivity in feces showed a higher variation between species (4-26 h to peak values). In all three species, the majority (>90%) of urinary metabolites were excreted as conjugates whereas the proportion of conjugated metabolites in feces was substantially lower and more variable. High pressure liquid chromatography (HPLC) analysis of urinary and fecal extracts revealed multiple peaks of radioactivity in all three individuals, but each with a distinctive pattern. Native T was excreted in only small amounts into the urine, whereas it was virtually absent in the feces of all three individuals. Three C17 group-specific enzymeimmunoassays using antisera against testosterone, 5alpha-androstane-17alpha-ol-3-one and androsterone were evaluated for their ability to discriminate immunoreactive androgen levels between intact males, castrated males and females based on measurements in urine and feces. In the marmoset, all assays (except for T in feces) clearly discriminated between test groups; in the chimpanzee significantly higher levels of androgen immunoreactivity in intact versus castrated males were measured in urine, but not feces. In the macaque, only the 5alpha-androstanolone measurement in feces discriminated between groups. Data on the results of a radiometabolism study using 3H-DHEA (a weak adrenal androgen) in a long-tailed macaque suggested that co-measurement of metabolites derived from T and DHEA in the assays tested might explain the difficulties in discriminating gonadal status in the two Old World primate species. Collectively, the data show that T metabolism in primates is highly complex and that no single method for noninvasive assessment of androgen status can be used for application across species. The importance of a proper validation of the methodology for each species is emphasised.

Androgens↗