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Tyrosine hydroxylase-immunoreactive neurons in the nucleus basalis of the common marmoset (Callithrix jacchus).

In the course of characterizing the distribution of putative catecholaminergic neurons in the brain of the common marmoset, we encountered a population of such cells in the basal forebrain. Tyrosine hydroxylase-immunoreactive neurons are abundant within the nucleus basalis magnocellularis throughout its entire rostrocaudal extent, but not in other cholinergic basal forebrain nuclei. Most tyrosine hydroxylase-immunoreactive cells are large and multipolar. Double staining with antibodies to choline acetyltransferase or nerve growth factor receptor confirmed that these tyrosine hydroxylase-immunoreactive neurons are cholinergic, and compose at least 40% of the nucleus basalis cholinergic cells. The presence of a catecholamine-synthesizing enzyme in the neurons that provide the major cholinergic input to the neocortex may have important consequences for cortical function, and may be relevant to the vulnerability of the nucleus basalis in certain neurodegenerative disorders.

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

Projections of the lateral terminal accessory optic nucleus of the common marmoset (Callithrix jacchus).

The connections of the lateral terminal nucleus (LTN) of the accessory optic system (AOS) of the marmoset monkey were studied with anterograde 3H-amino acid light autoradiography and horseradish peroxidase retrograde labeling techniques. Results show a first and largest LTN projection to the pretectal and AOS nuclei including the ipsilateral nucleus of the optic tract, dorsal terminal nucleus, and interstitial nucleus of the superior fasciculus (posterior fibers); smaller contralateral projections are to the olivary pretectal nucleus, dorsal terminal nucleus, and LTN. A second, major bundle produces moderate-to-heavy labeling in all ipsilateral, accessory oculomotor nuclei (nucleus of posterior commissure, interstitial nucleus of Cajal, nucleus of Darkschewitsch) and nucleus of Bechterew; some of the fibers are distributed above the caudal oculomotor complex within the supraoculomotor periaqueductal gray. A third projection is ipsilateral to the pontine and mesencephalic reticular formations, nucleus reticularis tegmenti pontis and basilar pontine complex (dorsolateral nucleus only), dorsal parts of the medial terminal accessory optic nucleus, ventral tegmental area of Tsai, and rostral interstitial nucleus of the medial longitudinal fasciculus. Lastly, there are two long descending bundles: (1) one travels within the medial longitudinal fasciculus to terminate in the dorsal cap (ipsilateral >> contralateral) and medial accessory olive (ipsilateral only) of the inferior olivary complex. (2) The second soon splits, sending axons within the ipsilateral and contralateral brachium conjunctivum and is distributed to the superior and medial vestibular nuclei. The present findings are in general agreement with the documented connections of LTN with brainstem oculomotor centers in other species. In addition, there are unique connections in marmoset monkey that may have developed to serve the more complex oculomotor behavior of nonhuman primates.

Animals↗

Correlations among measures of playfulness and skillfulness in captive common marmosets (Callithrix jacchus jacchus).

Infant sensorimotor and social skills, playfulness, and nonplayful behaviors were measured in common marmosets from 6 to 22 weeks old. Different measures of skill showed a low concordance, implying that skill is a multiple rather than unitary attribute. Significant correlations were found between the amount of social play infants performed from 11 to 13 weeks of age and their performance at 14 weeks in (1) competitive food tests with their mothers, and in (2) their ability to negotiate an obstacle for a food reward. Significant correlations were also found between these skills and nonplayful behaviors, however. Comparable analyses at other ages revealed few significant correlations, suggesting that the association between social play and skills is restricted to the age when infants are rapidly becoming independent of their caregivers both for locomotion and food. Age-specific correlations occurred between changes in levels of skills and both playful and nonplay behaviors. Our results are consistent with the hypothesis that social play promotes the development of skills, but alternative explanations are possible.

Animals↗

Effects on the behavior of infant common marmosets (Callithrix jacchus) of separation from caregivers and of drug-induced reduction in caregiver responsiveness.

The effects of separating 4-week-old twin marmosets for 8 days from their families are compared with the effects of leaving 4-week-old infants with their families, but reducing the responsiveness of their caregivers for 8 days by administration of the tranquilizer fluphenazine decanoate. Both treatments reduce infant mobility, abolish play, and increase the time that infants spend with each other. During the period after the termination of the treatment, both treatment groups continue to play and move less than controls, and try to climb onto the mothers more frequently. These results are consistent with the hypothesis that the principal factor precipitating disturbed behaviors in infant monkeys subjected to long-term separation is disruption of the infant-caregiver relationship rather than the separation itself. Some post-treatment differences occur between separated and tranquilized groups. Notably, reunion after separation appears to involve a marked readjustment of the behavior of all family members to the return of the infants, whereas withdrawal of the tranquilizer does not.

Animals↗

The diagnostic usefulness of isocitrate dehydrogenase (ICDH) in the marmoset (Callithrix jacchus).

Marmosets were given either a hepatotoxin, carbon tetrachloride, orally or an i.m. injection of a mytoxin, chlorpromazine. Although muscle damage alone caused small increases in the plasma levels of lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase and isocitrate dehydrogenase (ICDH), only the isoenzyme analysis of ICDH can differentiate definitely between liver and muscle damage. Only very severe muscle damage can increase the plasma concentration of this enzyme but, in this case, the elevation of plasma creatinine kinase levels helps differentiation. It is recommended that the elevation of ICDH is the most specific indicator of hepatic damage in the marmoset.

Alanine Transaminase↗

Antiparkinsonian activity and dyskinesia risk of ropinirole and L-DOPA combination therapy in drug naïve MPTP-lesioned common marmosets (Callithrix jacchus).

De novo administration of long-acting dopamine agonists, such as ropinirole, to patients with Parkinson's disease or to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated subhuman primates produces a lower incidence of dyskinesia than occurs with L-DOPA. This study compares the intensity of dyskinesia produced by combinations of L-DOPA and ropinirole and by these drugs alone, using the MPTP-treated common marmoset model of Parkinson's disease. The objective is to determine the optimum therapeutic strategy for the long-term control of Parkinson's disease with a minimal risk of dyskinesia. MPTP-treated marmosets received either L-DOPA alone, ropinirole alone, or one of two combinations of these drugs (either L-DOPA dominant or ropinirole dominant) daily for 28 days in doses titrated to produce a similar improvement in disability and increase in locomotion. In the group receiving L-DOPA alone, there was a trend for peak dose locomotor activity to increase and the duration of drug effect to decline over the period of the study. L-DOPA alone induced marked dyskinesia over the period of treatment, in contrast to ropinirole which produced a low intensity of involuntary movements. The L-DOPA dominant combination initially produced little dyskinesia, but this became increasingly intense as the study progressed. In contrast, the ropinirole dominant combination produced no greater intensity of dyskinesia than was produced by ropinirole alone. These data suggest that in early Parkinson's disease, the use of ropinirole alone or in combination with a low-dose L-DOPA might delay the induction of dyskinesias while improving motor performance.

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

The neuropathology of trimethyltin in the marmoset (Callithrix jacchus) hippocampal formation.

The effects of single and repeated doses of trimethyltin (TMT) treatment on the central nervous system (CNS) of the marmoset were investigated. For the acute-dose experiment adult animals were administered 3 mg/kg of TMT chloride (ip) and were then observed for changes in behavior. Within 24 hr postinjection all animals developed tremors, ataxia, and unresponsiveness. Half of the animals had severe clinical deterioration and died at 2 to 3 days following treatment. Surviving marmosets were sacrificed and the brain was subsequently perfusion-fixed for light microscopic examination. Neuronal degeneration was observed in many cells of the Ammon's horn and fascia dentata of the hippocampus. For the chronic-dose experiment, adult marmosets received (ip) weekly doses of 0.75 mg/kg of TMT chloride for 24 weeks. No evident clinical signs or behavioral changes were observed in any of the treated animals. Histological examination revealed neuropathological changes comparatively similar but less severe than those observed in the acute-treated animals. The differences in toxicity effects between acute and chronic TMT administration are compared and discussed.

Animals↗

Effects of testosterone propionate upon the sexual and aggressive behavior of adult male marmosets (Callithrix jacchus) castrated as neonates.

In New World monkeys of the family Callitrichidae (marmosets and tamarins), females frequently give birth to dizygotic twins. Twins share a placental circulation throughout fetal development and are hemopoietic chimeras. Despite this, there is no masculinization (freemartinism) in females which develop next to a male co-twin. It has been suggested that the organizing effects of testicular androgen upon sexual differentiation of the brain occur mainly during early postnatal development in male callitrichids, rather than in utero. However, this report demonstrates activation of masculine copulatory behavior by testosterone propionate (TP) administered to adult male marmosets (N = 8) which were castrated in infancy (between Days 1-7). Effects of neonatal castration upon aggressive behavior during pair tests with females (high frequencies of aggression) and intact adult males (low frequencies of aggression) were also reversed by TP treatment in adulthood. While early postnatal androgen secretion plays an important role in behavioral development in marmosets, it appears that a substantial degree of neural sexual differentiation occurs in utero in males of this callitrichid species.

Aggression↗

Quantitative receptor autoradiography of eight different transmitter-binding sites in the hippocampus of the common marmoset, Callithrix jacchus.

The regional and laminar distributions of eight different transmitter-binding sites were measured in the marmoset hippocampus by means of quantitative in vitro receptor autoradiography. Receptors for 5-HT1, L-glutamate, N-methyl-D-aspartate (NMDA) and GABAA were similarly distributed. The highest concentrations of these receptors were found in the pyramidal layer of CA1 and the molecular layer of the dentate gyrus. The 5-HT2 receptors showed the highest concentrations in the oriens layer of CA2. The highest concentrations of muscarinic M1 receptors were seen in the pyramidal layer of CA1. Muscarinic M2 receptors were most densely concentrated in the pyramidal layers of CA1, CA2 and CA3. The noradrenergic alpha 1 receptors were most densely packed in the radiatum-lacunosum-molecular layer of CA2 and the molecular layer of the dentate gyrus. Statistically significant co-distributions of serotoninergic, glutamatergic and GABAergic receptors point to possible interactions between these receptor systems in the same hippocampal regions and layers. Comparisons of marmoset distribution patterns for GABAA, NMDA, L-glutamate and 5-HT1 receptors with those in human hippocampi and those of other primates showed similarities between them. Clear differences in the patterns of alpha 1, M1, M2 and 5-HT2 receptors could be seen between marmoset and human hippocampi, indicating a high degree of species specificity in a presumably "conservative" brain region. More similarities, however, could be found between marmoset and human hippocampi than between those of rat and human brains, especially in relation to 5-HT1 and GABAA receptors and L-glutamate-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intercellular communication between cultured granulosa cells of the marmoset (Callithrix jacchus).

The influence of follicle-stimulating hormone, forskolin, insulin-like growth factor type I, epidermal growth factor, and 12-tetradecanoyl-phorbol-13-acetate on marmoset granulosa cell communication via gap junctions was investigated by morphological means and microinjection of carboxyfluorescein. Gap junctions between neighbouring granulosa cells were present in all groups. The number, but not length, of gap junctions between marmoset granulosa cells increased when the cells had been treated with follicle-stimulating hormone, insulin-like growth factor type I, and follicle-stimulating hormone plus insulin-like growth factor type I. No effect on gap junctions was seen, after exposure of the cells to the other three substances. Carboxyfluorescein and counting of the surrounding labelled cells showed that supplementation with follicle-stimulating hormone, forskolin, insulin-like growth factor type I and epidermal growth factor from the beginning of cultivation led to an increase in stained cells after 48 h. When treatment was started in 48 h cultures the substances reached their maximal activity within 30 min (forskolin and epidermal growth factor) or 3 h (follicle-stimulating hormone and insulin-like growth factor type I). Spreading of the fluorescent dye was inhibited when the medium was supplemented with 12-tetradecanoyl-phorbol-13-acetate. This effect was maximal after 30 min. Additive effects regarding the coupling of the cells were seen by combining of epidermal growth factor with follicle-stimulating hormone, but not with insulin-like growth factor type I or forskolin plus follicle-stimulating hormone.

Animals↗

A conveyor belt task for assessing visuo-motor coordination in the marmoset (Callithrix jacchus): effects of diazepam, chlorpromazine, pentobarbital and d-amphetamine.

A conveyor belt task for assessing visuo-motor coordination in the marmoset is described. Animals are motivated by apple, a preferred food, under a state of minimal food deprivation. The apparatus used was designed to test animals within their home cages and not restrained in any way, thus avoiding possible confounding factors associated with restraint stress. Stable baseline levels of performance were reached by all animals in a median of 24 sessions. Performance was shown to be differentially sensitive to the effects of four psychoactive drugs. Moderate doses of diazepam, chlorpromazine and pentobarbital disrupted visuo-motor coordination in a dose-related manner. The possibility that disruption of performance observed at higher doses may have resulted from non-specific actions of these drugs such as decreases in feeding motivation were not supported by results from ancillary experiments. Changes in performance characteristic of high dose effects were similar in nature to changes observed when the degree of task difficulty was increased. Doses of d-amphetamine up to and including those reported to produce signs of stereotypy failed to influence performance. The potential of the conveyor belt task for measuring visuo-motor coordination in both primate and rodent species is discussed.

Animals↗

Investigations into the induction of chronic experimental arthritis in the common marmoset (Callithrix jacchus).

In an attempt to produce a superior model of rheumatoid arthritis, experiments have been performed to investigate the ease of induction of experimental arthritis in marmosets by immunological means. Marmosets were sensitised with the following combinations of antigen and adjuvant: ovalbumin in Freund's complete adjuvant (FCA), ovalbumin in FCA + Bordetella pertussis, methylated-BSA in FCA + B. pertussis or human fibrin in FCA + B. pertussis, and subsequently injected with the corresponding antigen in saline into one knee joint. Animals receiving ovalbumin, with or without B. pertussis, produced only a weak transient monoarticular synovitis. Animals receiving Met-BSA + B. pertussis produced a chronic synovitis but only mild erosive changes were apparent even 21 weeks after intraarticular injection. Animals receiving human fibrin produced a transient monoarticular synovitis of moderate intensity. These results indicate that the marmoset offers no obvious advantages over the rabbit for the induction of experimental rheumatoid arthritis.

Animals↗

The expression of sf-1/Ad4BP is related to the process of luteinization in the marmoset (Callithrix jacchus) ovary.

Expression of the nuclear receptor, steroidogenic factor-1 (SF-1/Ad4BP), was studied in a primate (marmoset) ovary using immunohistochemical, RT-PCR, and immunoblot techniques. The periovulatory phase was compared with the luteal phase. With PCR we found a marmoset homolog of SF-1/Ad4BP to be expressed in ovarian and other steroidogenic tissues. Characteristically, the periovulatory ovaries consisted of growing (non-luteinized) small follicles together with large luteinizing follicles and many corpora lutea accessoria (Clas), which had developed from atretic large follicles. During the luteal phase, true corpora lutea (Cls) were additionally found. In general, we found that small follicles were devoid of any immunoreactivity of SF-1/Ad4BP. In large follicles, the luteinizing theca and granulosa cells express SF-1/Ad4BP. All luteal cells of Clas showed a nuclear staining in both ovary types. In Cls, only a few luteal cells were positive. Large follicles of different sizes showed no differences in expression level, as evidenced by immunoblot analysis. Our results indicate that SF-1/ Ad4BP participates in the activation of genc transcription during the onset of luteinization and that Clas are essential for ovarian luteal function.

Animals↗

Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus).

RATIONALE: There is a requirement to ensure that UK armed forces are provided with the best possible medical countermeasures to prevent or mitigate the effects of exposure to nerve agents. When pretreatments are under consideration, it is of particular importance to ensure that they do not in themselves give rise to adverse effects and do not exacerbate the effects of agent exposure. OBJECTIVES: The present study was designed to address these considerations for a combination of physostigmine and scopolamine as a potential pretreatment regimen. METHODS: Common marmosets were trained to perform a two-choice discrimination serial reversal task, and baseline data were collected. Subjects received a dose of either soman or sarin after 2 weeks of pretreatment with either saline or physostigmine and scopolamine via miniosmotic pump. RESULTS: No effects of physostigmine and scopolamine were seen on task accuracy or response rates. Neither accuracy of reversal performance nor number of responses made were significantly changed by administration of either soman or sarin subsequent to pretreatment with physostigmine/scopolamine. In the groups pretreated with saline, performance of the behavioural task, in terms of responses made, was virtually abolished on the day the OP was administered, but a significant increase in accuracy of performance was seen over the 2- to 14-day period following administration. CONCLUSIONS: A combination of physostigmine and scopolamine, which is known to protect against nerve-agent lethality, offers protection against the effects of soman and sarin on behavioural performance, as measured by a discrimination reversal task. The improved performance observed following nerve agent requires further investigation.

Animals↗

Neurofilament protein expression in the geniculostriate pathway of a New World monkey ( Callithrix jacchus).

We examined the expression profile of non-phosphorylated neurofilament protein in the dorsal lateral geniculate nucleus (LGN) and striate cortex (V1) of a New World simian, the marmoset monkey, using the monoclonal antibody SMI-32. The overall distribution of neurofilament protein in the marmoset resembled that previously described in Old World monkeys. While immunostained neurones were observed throughout the LGN, there were clear laminar differences in terms of both cellular and neuropil labelling. Neurones in the magnocellular layer cells stained more densely than those in the parvocellular layers. The marmoset's well-defined koniocellular layers showed an overall light stain of both neurones and neuropil. In V1, densely stained pyramidal cells and heavy neuropil label were observed in the two sublayers that send projections to the middle temporal area (MT): a supragranular band located in layer 3C (Brodmann's layer 4B) and an infragranular band located near the top of layer 6. More lightly stained, small pyramidal cells were also found in layer 3Balpha. Accordingly, in both New World and Old World monkeys the expression of neurofilament protein is correlated with specific functional subdivisions of the geniculocortical pathway. In particular, projection neurones associated with fast-conducting pathways to the extrastriate 'dorsal stream' appear to contain higher levels of this protein.

Animals↗

Midbrain connections of the olivary pretectal nucleus in the marmoset (Callithrix jacchus): implications for the pupil light reflex pathway.

Midbrain projections of the pretectal olivary nucleus (PON) were studied in the marmoset, a New World primate. The fluorescent retrograde tracers Fluoro-Gold (FG) and Fast Blue (FB) were injected into the Edinger-Westphal (EW) nucleus and the lateral terminal nucleus (LTN), respectively. EW nucleus injections resulted in retrograde labeling of significant numbers of FG-positive neurons of the PON as well as a small number of cells in the LTN. LTN injections led to labeling of a population of singly-labeled cells seen dispersed through the larger population of FG-labeled somata within the contralateral PON. The ipsilateral PON was devoid of FB-labeled somata, whereas the adjacent nucleus of the optic tract (NOT) contained FB-labeled cells. These findings show that a large number of PON neurons project directly to the oculomotor complex. Additionally, the study shows the presence of a separate population of PON neurons projecting to the contralateral LTN. This, combined with our earlier observation that LTN neurons project to the EW nucleus in the marmoset (see main text for reference), lends support to the presence of separate direct and indirect pupillary light reflex pathways from the PON to the nucleus of EW.

Animals↗

Naturally occurring and experimentally induced beta-amyloid deposits in the brains of marmosets (Callithrix jacchus).

Cerebral beta-amyloid occurs in elderly animals of some species and in Alzheimer's disease. Previously, we injected 3 young marmosets intracerebrally with brain tissue from a patient with Alzheimer's disease. Six years later, when the monkeys were middle aged, we found moderate numbers of intracerebral plaques and cerebrovascular deposits containing beta-amyloid. We have re-examined these brains and those of 10 other marmosets injected with brain homogenate containing beta-amyloid, and have found some beta-amyloid in animals injected more than 4 years previously. We have found beta-amyloid in 4 of 26 elderly control marmosets, but not in 9 young to middle-aged control marmosets. The beta-amyloid found in middle aged marmosets injected with Alzheimer brain tissue was, therefore, not a consequence of their age. Deposits in large cerebral vessels in elderly marmosets, and in marmosets previously injected with brain tissue containing beta-amyloid, reacted with antibodies to Abeta and Abeta1-40; plaques and microvessel deposits reacted with antibodies to Abeta and Abeta1-42.

Age Factors↗