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The relationship between cone pigments and behavioural sensitivity in a New World monkey (Callithrix jacchus jacchus).

Microspectrophotometric measurements of visual pigments and behavioural measurements of spectral sensitivity are reported for individual marmosets from 3 family groups. The sex differences and polymorphism that characterise the long-wave cone pigments in this species are well reflected by variations in the behavioural sensitivities. With one exception, the pattern of inheritance is compatible with a genetic model in which the long-wave pigment is specified by a single polymorphic locus on the X-chromosome. Measurements are also reported for the spectral absorbance of the marmoset lens, and these are used to reconstruct short-wave behavioural sensitivity from the microspectrophotometric measurements of the short-wave cones.

Animals↗

Termination of pregnancy in common marmosets (Callithrix jacchus) following administration of antiserum to chicken riboflavin carrier protein.

The presence of protein(s) which is immunologically and functionally similar to the well characterised avian riboflavin carrier protein has been demonstrated in female common marmosets during pregnancy. The protein(s) that interacts with [14C]riboflavin has an immunological homology to chicken riboflavin carrier protein. The termination of pregnancy in four out of six marmosets following administration of antiserum to chicken riboflavin carrier protein supports the hypothesis that vitamin carrier protein ensures an uninterrupted supply of the vitamin to the growing embryo and that immunoneutralization of maternal riboflavin carrier protein leads to fetal death and termination of pregnancy.

Animals↗

The distribution of glial fibrillary acidic protein and vimentin in postnatal marmoset (Callithrix jacchus) brain.

Antisera to glial fibrillary acidic protein (GFAP) and vimentin were used to elucidate the distribution of these intermediate filament proteins in postnatal marmoset brains of various ages. The ependyma of the lateral ventricles was unique in being equally immunoreactive for both GFAP and vimentin at all ages. Vimentin alone was consistently demonstrated in endothelial and leptomeningeal cells at all ages. In neonates, vimentin immunoreactivity greatly exceeded that of GFAP and was located primarily in radial glia in the subependymal plate of the anterior cerebrum. Their vimentin-positive processes formed thick fascicles in the corpus callosum but separated into fine fibres on entering the cortex. GFAP immunoreactivity in these cells and processes was very limited. With age, GFAP-positive cells increased in number and displayed the typical stellate appearance of astroglia. The vimentin-positive radial glial population decreased considerably during this period and by 6 months had virtually disappeared. The GFAP reaction in adult brain was even more widespread, largely due to the increased number of positive astrocytes in the white matter. Vimentin immunoreactivity in the adult was greatly diminished and positive radial glia were not detectable. A major change in intermediate filament protein expression, therefore, occurs in the early postnatal period and probably reflects phases in the differentiation of radial glial precursors into astrocytes.

Animals↗

Cell proliferation in the subependymal layer of the postnatal marmoset, Callithrix jacchus.

Cells of the subependymal layer (SEL) have been shown to be capable of continued postnatal cell division throughout life in rodents. To determine if the primate brain behaves similarly, proliferative activity in the SEL of the marmoset has been investigated by tritiated thymidine autoradiography and bromodeoxyuridine immunocytochemistry. Both methods revealed the presence of DNA-synthesizing cells at all postnatal ages studied. The labelling index (LI), low at birth, reached a peak of almost 4% at one month but decreased gradually thereafter. In animals older than two years the LI was extremely low and labelled cells were rarely seen anywhere in the brain. The cell density of the SEL, in contrast to the low LI, was highest in neonates and decreased linearly with increasing age. Bromodeoxyuridine immunoreactivity revealed the distribution of proliferating cells in the SEL and neighbouring regions. Such cells were most abundant around the anterior lateral ventricle where the SEL was most evident. Proliferating cells were numerous in neonates, though not adjacent to the ependyma where counts for the LI were made, and were mainly located dorsally and ventrally at the junctions of the corpus callosum and caudate nucleus.

Aging↗

Effects of variable linoleate intake on aortic PGI2-like activity and fatty acid composition: difference between rat and marmoset (Callithrix jacchus).

Two animal species, the laboratory rat and a non-human primate (the common marmoset) were compared with respect to the influence of dietary lipid supplementation on both fatty acid composition and prostanoid synthetic capacity of aorta. Standard chow (REF. diet) was supplemented (12% w/w) with either sheep fat (SF) or sunflower seed oil (SSO). Differences were apparent in the aortic phospholipid fatty acids from both animal models, as a result of the diet, although the type and the extent of changes displayed a considerable species variation. For example, after the SSO diet, the proportion of linoleic acid in rat aorta displayed only a modest increase whilst in marmosets it was doubled. No change was apparent in the proportion of arachidonic acid in rats, whereas the marmosets showed a reduction (P less than 0.05) with both lipid supplements. Rats fed the SF diet showed a considerable increase in aortic PGI2-like activity compared to REF. And SSO supplemented groups. In contrast, no dietary induced changes were observed in the aorta from marmosets despite compositional changes. The results indicate no direct association between the synthesis of PGI2-like activity and membrane lipids and demonstrate the need for careful selection of the proper animal model, particularly in nutritionally orientated experiments.

Animals↗

Dietary lipids and adipose tissue fatty acids in the marmoset monkey (Callithrix jacchus).

The fatty acid composition of marmoset monkey perirenal fat was examined after long-term feeding of different lipid supplemented diets. Saturated fatty acid supplementation significantly reduced linoleic acid; n-6 polyunsaturated fatty acid (PUFA) supplementation decreased oleic acid but did not reduce the saturated fatty acid content of perirenal fat. Dietary supplementation with fish oil also reduced the level of linoleic acid but increased the level of palmitic acid as well as that of the long-chain n-3 PUFAs. Perirenal fat levels of linoleic acid and docosahexaenoic acid are reliable measures of n-6 and n-3 PUFA intake respectively, but the levels of saturated fatty acids palmitic and stearic do not accurately reflect the marmosets dietary intake.

Adipose Tissue↗

A novel population of tyrosine hydroxylase immunoreactive neurones in the basal forebrain of the common marmoset (Callithrix jacchus).

We have observed in the basal forebrain of the common marmoset a group of neurones which display tyrosine hydroxylase immunoreactivity (THir) with three different polyclonal antibodies and one monoclonal antibody, and which express TH mRNA as shown by in situ hybridization histochemistry. The population of cells is composed of large multipolar neurones and is located predominantly in the substantia innominata and at the ventral, medial and lateral margins of the external segment of the globus pallidus. The cell morphology and the distribution of THir cells corresponds closely to the caudal portion of the nucleus basalis of Meynert. Adjacent sections demonstrate both THir and choline acetyltransferase immunoreactivity in the cells in this group, as well as strong acetylcholinesterase activity but not dopamine immunoreactivity. These observations indicate that many cholinergic neurones in the posterior nucleus basalis of Meynert of the marmoset contain tyrosine hydroxylase, and suggest that both acetylcholine and catecholamine may be synthesised as co-localised neurotransmitters within the same magnocellular neurones. We observe no THir cells in similar areas of the basal forebrain of either rhesus or talapoin monkeys.

Animals↗

Purification and properties of cytochrome P-450 from liver microsomes of phenobarbital-treated marmoset monkeys (Callithrix jacchus).

One form of cytochrome P-450 from phenobarbital-induced marmoset liver was purified to apparent electrophoretic homogeneity and compared with the major inducible form isolated from rat liver. Whereas spectral properties and molecular weights, as well as catalytic activities towards aminopyrine and ethylmorphine N-demethylation are quite similar, rates of O-dealkylation with enzymes from the two species are considerably different. While ethoxycoumarin deethylation for the marmoset cytochrome is about one-fortieth of that for the rat, ethoxyresorufin and even pentoxyresorufin dealkylations for the marmoset form are not detectable. By contrast, aldrin epoxidation as catalyzed by this cytochrome is about three times as high as that obtained from the rat.

Aldrin↗

Calcium-binding proteins in the spiral ganglion of the monkey, Callithrix jacchus.

Calcium-binding proteins can act as intermediaries between changing levels of free intracellular calcium ions and the physiological response of neurons. Some of these proteins, among them calbindin (CB), calretinin (CR) and parvalbumin (PV), can act as calcium buffers. A survey of previous studies in rodents and human fetuses leads to the impression that many spiral ganglion cells co-express CB, CR, and PV. The findings of the present study suggest that, in the adult marmoset, the expression of CB is restricted to a small number of cells, most likely type II ganglion cells, and that at least some of the numerous type I ganglion cells co-express CR and PV. In the neonate marmoset, large numbers of putative type I ganglion cells from the apical cochlear turn transiently expressed a light and granular labeling for CB-like immunoreactivity, in addition to the cells we believe to be type II ganglion cells exhibiting a strong and solid CB-like staining. The spiral ganglion cells in all developmental stages co-expressed the mitochondrial enzyme cytochrome oxidase. Furthermore, a small population of CB-LI axons of unknown origin was found to terminate near the CB-immunoreactive ganglion cells.

Animals↗

New hyperprolactinemia and anovulation model in common marmoset (Callithrix jacchus) and effect of cabergoline.

We aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in common marmosets. The serum prolactin level gradually increased during the twice-daily administration of sulpiride and reached a plateau after 4 days. Sulpiride produced as big a response at 10 mg kg(-1) as at 50 mg kg(-1). In this study, the length of the ovarian cycle was approximately 30 days in normal common marmosets. Serum progesterone and estradiol levels showed no consistent change during the first 2 months of treatment with sulpiride. When treatment with sulpiride had been continued for more than 2 months, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle and absence of ovulation was recognized by laparoscopy. A single oral administration of cabergoline (at doses between 0.01 and 0.1 mg kg(-1)) dose dependently reduced the elevated serum prolactin level. Bromocriptine (at an oral dose of 10 mg kg(-1)) also reduced the serum prolactin level at 4 and 8 h after its administration. With bromocriptine, the prolactin level had recovered at 24 h, but with cabergoline at doses of 0.05 mg kg(-1) or more, it had still not recovered at 48 h. In anovulatory common marmosets, oral administration of cabergoline at a daily dose of 0.05 mg kg(-1) restored ovarian function and resulted in ovulation in 100% of the group (following a reduction in the serum prolactin level). Bromocriptine at a daily oral dose of 10 mg kg(-1) resulted in ovulation in 67% of the group, but this dose was about 200 times higher than the dose of cabergoline. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. It is suggested that, in this anovulatory model in common marmosets, cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist, and thus could be a useful drug for the treatment of galactorrhea and hyperprolactinemic amenorrhea and/or anovulation.

Animals↗

Controlled ovulation in the marmoset monkey (Callithrix jacchus) with human chorionic gonadotropin following prostaglandin-induced luteal regression.

Controlled induction of ovulation in the marmoset monkey was attempted with a single injection of human chorionic gonadotropin (hCG; 50 IU) given on day 7 after prostaglandin-induced luteal regression. Animals given hCG (n = 12) ovulated within a 2-day period (days 9 and 10 after prostaglandin) compared with a 4-day period (days 9 to 12) in the control group (n = 12). The mean interval to ovulation was similar in both groups. There was no difference in the timing of the preovulatory estradiol (E2) peak between groups, although E2 levels on the day of hCG injection were lower than in controls on the day of the onset of the luteinizing hormone surge. All animals given hCG ovulated and 11 of 12 became pregnant. Ten of 11 embryos recovered surgically from six of these animals were normal blastocysts; 5 of the remaining 6 animals carried pregnancies to term. The results are of practical importance for experiments involving follicular and oocyte maturation and the collection and transfer of embryos.

Animals↗

Births following the transfer of cultured embryos obtained by in vitro and in vivo fertilization in the marmoset monkey (Callithrix jacchus).

The aim of this study was to determine whether marmoset monkeys are a suitable primate model for in vitro fertilization (IVF), embryo culture, and transplantation studies. A prostaglandin analogue given in early pregnancy and human chorionic gonadotropin given near the end of the ensuing follicular phase were used for controlling the reproductive cycle, timing oocyte collection, and synchronizing the cycles of oocyte donors and embryo recipients. Five embryos obtained by IVF were transferred at early stages to the uterus of three recipients, and two gave birth to live infants. Some of the embryos were cultured to advanced blastocyst stages. In vivo fertilized oocytes were also cultured and transferred to two recipients, and one gave birth. We concluded that the marmoset is one of the best primates for such investigations.

Animals↗

Increased ACTH and cortisol secretion after interleukin-alpha injection in the common marmoset (Callithrix jacchus jacchus).

We have studied the effect of intravenous injection of interleukin-1 (dose range: from 0.25 to 4.5 microg/kg of body weight) on plasma ACTH and cortisol levels in the marmoset, a primate paradygm of peripheral glucocorticoid resistance. Blood sampling were collected and body temperature recorded 0, 15, 30, 60, 120, 180, 240 and 300 min after injection. Interleukin-1 stimulated secretion of ACTH in a dose-dependent fashion. Maximal secretion occurred 120 min after injection, and lasted up to 240 min. Plasma ACTH levels returned to baseline 300 min after interleukin-1 injection. Plasma cortisol levels were related to ACTH levels. Body temperature elevation, which occurred 10-15 min after injection was dose-dependent, and lasted 3 h. Results suggest that the pyrogenic effect of interleukin is associated, in the marmoset, with integrated activation of the hypothalamic-pituitary-adrenal axis. In light of the proneness of marmosets to hyperimmune disorders, our data are consistent with the hypothesized central biological role of IL-1, as well as the pathophysiological relevance of the neuro-endocrine-immune cross-talk during the acute phase response.

Adrenocorticotropic Hormone↗

Psychosocial stress and urinary cortisol excretion in marmoset monkeys (Callithrix kuhli).

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the hallmarks of the physiological responses to psychosocial stressors. The most common method of assessing HPA function is via the measurement of plasma cortisol levels. However, venipuncture involves capture and restraint, which can modify HPA function. We validated a noninvasive procedure for monitoring HPA responses to stressors by measuring excretion of free urinary cortisol. Samples collected throughout the day displayed marked circadian variation, with low cortisol values in first-void samples, followed by a mid-morning peak in cortisol excretion. Concentrations of excreted cortisol declined throughout the day. Exposing marmosets to mild and moderate stressors (11 h isolation in a small cage and manual restraint) increased excreted cortisol concentrations in a dose-dependent fashion: isolation in a small cage led to elevated cortisol in afternoon samples, while manual restraint and isolation produced elevated cortisol in both morning and afternoon samples. The marmoset HPA is differentially sensitive to rather subtle variations in stressors, and these results show that urinary cortisol excretion is a valid and sensitive index of the HPA response to these stressors.

Animals↗

Relationship between expression of integrins and granulosa cell apoptosis in ovarian follicles of the marmoset (Callithrix jacchus).

DNA fragmentation (apoptosis) was studied during the follicular, periovulatory and luteal phase in the marmoset monkey ovary by means of terminal transferase mediated in situ nick end labeling, and correlated with immunohistochemical localization of integrins (beta 1, alpha 2 and alpha 6 subunits). For this purpose a double-labeling technique was developed. During all phases, apoptosis of granulosa cells was exclusively restricted to tertiary follicles displaying advanced stages of atresia (as morphologically determined). During early stages of atresia in tertiary follicles, indicated by widened intercellular spaces, no apoptosis was seen. Staining intensities for integrins beta 1 and alpha 6 were strong in intact primordial/primary, secondary and tertiary follicles. Integrin expression of granulosa cells was weak in atretic tertiary follicles but not in atretic primary or secondary follicles. Double labeling revealed that DNA fragmentation was solely found in granulosa cells of tertiary follicles displaying faint or absent staining for both integrin subunits. During the periovulatory and the luteal phase, granulosa cells of atretic tertiary follicles bordering on the basal membrane, which were referred to as luteinizing cells, expressed the beta 1 subunit as well as the alpha 2-integrin subunit whereas granulosa cells neighboring to the antrum were apoptotic and negative for integrin immunoreactivity. In summary, early atresia of tertiary follicles is first characterized by morphological alterations as wide intercellular gaps, without any signs of granulosa cell apoptosis. Advanced stages of atresia, in tertiary follicles however, are accompanied by apoptosis of granulosa cells and a faint or absent staining for integrin subunits beta 1 and alpha 6. According to recent in vitro findings, our results point to a possible relation between granulosa cell apoptosis of tertiary follicles and integrin expression in ovarian marmoset follicles.

Animals↗

The effects of spectacle wear in infancy on eye growth and refractive error in the marmoset (Callithrix jacchus).

We made a comprehensive study, involving observations on 45 marmosets, of the effects on ocular growth and refraction of wearing spectacles from the ages of 4-8 weeks. This period was within the period early in life when the eye grows rapidly and refraction changes from hyperopia to its adult value of modest myopia. In one series of experiments we studied the effect of lenses of powers -8, -4, +4 and +8D fitted monocularly. In another series of experiments we studied the effect of lenses of equal and opposite powers fitted binocularly, with the two eyes alternately occluded, so as to give an incentive to use both eyes, and in particular to accommodate, for at least part of each day, through the negative lens. The vitreous chamber of eyes that wore negative lenses of -4D or -8D, combined with alternate occlusion, elongated more rapidly than that of the fellow eye (negative lens eye-positive lens eye, 0.21 +/- 0.03 mm (S.E.M.), P < 0.01 and 0.25 +/- 0.06 mm, P < 0.05, respectively) and became relatively more myopic (2.8 +/- 0.26D, P < 0.01 and 2.4 +/- 0.61D, P < 0.05 respectively). Eyes that wore -4D lenses monocularly elongated more rapidly and became myopic than fellow eyes. Eyes that wore +4D or +8D lenses were less strongly affected: animals that wore +8D lenses monocularly (without alternate occlusion) developed a slight relative hyperopia (0.99 +/- 0.21D, P < 0.01), with the more hyperopic eyes also slightly shorter (0.09 +/- 0.05 mm) than their fellow eyes, but eyes wearing +4D lenses were not significantly different from their fellow eyes. Animals that wore -8D lenses monocularly (without alternate occlusion) developed a slight relative hyperopia after three weeks of lens-wear (0.85 +/- 0.26D, P < 0.05). These were the only eyes that responded in a non-compensatory direction to the optical challenge of spectacle wear, and we interpret this effect as one due to visual deprivation. After the removal of lenses, the degree of anisometropia slowly diminished in those groups of animals in which it had been induced, but in the three groups in which the largest effects had been produced by lens-wear the overall mean anisometropia (0.68 +/- 0.24D, P < 0.01) and vitreous chamber depth (VCD) discrepancy (0.09 +/- 0.03 mm, P < 0.01) were still significant at the end of the experiments, when the animals were 273 days old. The reduction of anisometropia in these groups was associated with an increase in the rate of elongation of the vitreous chamber in the eyes that had previously grown normally i.e. the less myopic eyes grew more rapidly than their fellow eyes: in the seven weeks following lens-wear these eyes became more myopic and longer than normal eyes (refraction P < 0.001; VCD P < 0.001). Control experiments showed that occlusion of one eye for 50% of the day had no effect on eye growth and refraction, and therefore that alternate occlusion itself had no effect.

Age Factors↗

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

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

Acute Disease↗