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At least 1,639 records · Page 91Linked to original sources
PubMed2003

Orientation mosaic in barn owl's visual Wulst revealed by optical imaging: comparison with cat and monkey striate and extra-striate areas.

Using the technique of intrinsic signal optical imaging, orientation preference maps were obtained from the Wulst of the barn owl in the area that represents central vision, and from the visual cortices (V1 and V2) of cat and marmoset monkey. Iso-orientation domains in barn owl's visual Wulst were patch-like structures with an inter-patch distance of approximately 0.9 mm, arranged in a pinwheel-like manner around singularity points. The size of the iso-orientation domains in barn owl was larger than those found in area V1, but comparable to those found in area V2, of cat and monkey. Superficial layers of the owl visual Wulst may be equivalent to extra-striate visual areas of primates and carnivores, as already suggested by electrophysiologists discussing the much increased radial dimensions of the Wulst compared with neocortex in mammals.

Animals↗
PubMed2003

Alterations in m-RNA expression for Cu,Zn-superoxide dismutase and glutathione peroxidase in the basal ganglia of MPTP-treated marmosets and patients with Parkinson's disease.

Alterations occurring in the antioxidant enzymes, copper, zinc-dependent superoxide dismutase (Cu,Zn-SOD) and glutathione peroxidase (GPX) following nigral dopaminergic denervation are unclear. We now report on the distribution and levels of m-RNA for Cu,Zn-SOD and GPX in basal ganglia of normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets, and in normal individuals and patients with Parkinson's disease (PD) using in situ hybridization histochemistry and oligodeoxynucleotide (single-stranded DNA) probes. Cu,Zn-SOD and GPX m-RNA was present throughout basal ganglia (nucleus accumbens, caudate-putamen, globus pallidus, substantia nigra) in the common marmoset, with the highest levels being in substantia nigra (SN). Following MPTP induced nigral cell loss, Cu,Zn-SOD m-RNA levels were decreased in all areas but the SNr, and particularly in SNc (71%, P<0.001). MPTP-treatment had no effect on GPX m-RNA expression in any area of basal ganglia. Cu,Zn-SOD and GPX m-RNA was also present in the normal human SN. In PD, however, Cu,Zn-SOD m-RNA was significantly decreased (89%, P<0.005) in SNc, and there was a near-complete loss of GPX m-RNA in both SNc (100%, P<0.005) and SNr (88%, P<0.005). The loss of Cu,Zn-SOD m-RNA in SNc in MPTP-treated marmosets and patients with PD suggests that it is primarily located in dopaminergic neuronal cell bodies. The loss of GPX m-RNA in SNc in PD also suggests a localisation to dopaminergic cell bodies, but the similar change in SNr may indicate its presence in dopaminergic neurites. In contrast, the absence of change in GPX m-RNA in MPTP-treated primates appears to rule out its presence in dopaminergic cells in this species, but this may only be apparent and may reflect increased expression in glial cells following acute toxin treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

Comparison of the neuroprotective effect of clomethiazole, AR-R15896AR and NXY-059 in a primate model of stroke using histological and behavioural measures.

Three experimental neuroprotective agents (clomethiazole, AR-R15896AR and NXY-059) have recently been tested in a primate model of acute ischaemic stroke. As the experimental techniques used in all three studies were similar and the compounds were administered at clinically relevant doses, a comparative analysis of the functional benefits of these drug-treatments has now been performed. Furthermore a more detailed histological analysis of the neuroprotection afforded by the drugs has also been made. NXY-059 produced almost twice the degree of neuroprotection than that seen following clomethiazole or AR-R15896AR. Protection by NXY-059 was seen in measurements of damage to cortex and white matter. Clomethiazole and AR-R15896AR provided less protection of cortex and white matter than NXY-059. Conspicuously, AR-R15896AR was without effect in sub-cortical regions. NXY-059 was the only compound to produce a major, statistically significant improvement in the motor deficit induced by the stroke. All three drugs also reduced the degree of spatial neglect 3 weeks after pMCAO, and 10 weeks later only NXY-059 still provided significant additional functional benefit to the spontaneous improvement seen in stroked control animals not receiving treatment. The overview of the behavioural effects and these new histological findings suggest that NXY-059 was by far the most effective neuroprotective agent of the three examined.

Animals↗
PubMed2003

Purkinje-like cells in the cochlear nucleus of the Common Tree Shrew (Tupaia glis) identified by calbindin immunohistochemistry.

The dorsal cochlear nucleus (DCN) of Tree Shrews (Tupaia glis; n=2) was examined by calbindin (CB) immunohistochemistry for the presence of Purkinje-like cells (PLCs), detected previously in only four different mammals. We found up to eight CB-immunoreactive PLCs in the left and right DCN, and a few axons, likely of PLC origin, that appeared to leave the DCN. These findings suggest that PLCs may have a wider distribution through mammalian species, and may represent more than just misrouted cells.

Animals↗
PubMed1997

Increased dopamine turnover in the putamen after MPTP treatment in common marmosets.

The differences in dopamine turnover rate between the putamen and the caudate nucleus in the striatum lesioned by a neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied in the common marmoset, a small New World monkey. Systemic administration of MPTP damaged equally and dose-dependently nigrostriatal dopaminergic neurons projecting both to the caudate nucleus and the putamen. The compensatory increase of dopamine turnover, however, occurred more prominently in the putamen than in the caudate. The neural connection and function of the caudate nucleus and the putamen have been differentiated anatomically or physiologically. The compensatory increase of dopamine turnover rate is another different aspect of functions between the caudate nucleus and the putamen. Dopaminergic neurons projecting to the putamen showed more prominent cell loss than those projecting to the caudate in Parkinson's disease or related disorders. The selective augmented turnover rate of lesioned dopaminergic neurons might be, at least partly, involved with selective degeneration of nigrostriatal neurons projecting to the putamen.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

Rapid changes in brainstem maps of adult primates after peripheral injury.

Cerebral cortical maps in adult primates reorganize within minutes-hours after peripheral injuries, but subcortical versus intracortical contributions to this rapid reorganization remain controversial. The present results show that injury of nerves to the hands of adult monkeys triggers rapid (minutes-hours) changes in maps of the hand in the brainstem main cuneate nucleus. These findings suggest that peripheral injury causes an initial concurrent reorganization of brainstem and cortical substrates and that early sensory changes emerge from reorganization involving multiple central levels.

Animals↗
PubMed1999

Effect of selegiline on dopamine concentration in the striatum of a primate.

Monoamine oxidase (MAO) has two subtypes, A and B, that have different distributions between the rodent and the human. In the striatum, dopamine (DA) of the rat seems to be metabolized by MAO A, and DA of the human is largely deaminated by MAO B. MAO in the striatum of common marmosets is also type B. Using in vivo microdialysis, we investigated the pharmacological activity of selegiline, a selective irreversible inhibitor of MAO B, in the striatum of marmosets. Intraperitoneal co-administration of selegiline (1 mg kg-1, i.p.) with levodopa/carbidopa (10/2.5 mg kg-1, i.p.) did not significantly increase extracellular concentration of DA in the striatum of common marmosets compared with control animals receiving levodopa/carbidopa alone. Daily pretreatment with 0.1 mg kg-1 (i.p.) selegiline for two weeks, however, dramatically increased extracellular concentration of DA to about seven times that of control animals treated with levodopa/carbidopa alone in marmosets. Such an increase in extracellular concentrations of DA could not be observed in a similar study with Wistar rats. This study showed that chronic administration of a small dose of selegiline caused a marked increase in extracellular DA concentration in the striatum of primates, but not in the rodents.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Severe learning impairment caused by combined immunotoxic lesion of the cholinergic projections to the cortex and hippocampus in monkeys.

Monkeys with immunotoxic lesions of both the basal nucleus of Meynert and the vertical limb of the diagonal band of Broca (NBM+VDB) lost cholinergic innervation throughout the cortex and hippocampus. They were impaired at learning discriminations between objects differing in either few, or many, attributes and at learning visuospatial conditional discriminations. Monkeys with immunotoxic lesions of the NBM lost cholinergic innervation of the neocortex only. Initially, they were unable to learn a simple visual discrimination where the stimuli differed in a limited number of attributes but they were unimpaired at learning discriminations between objects that differed in more attributes. They were mildly impaired at learning a visuospatial conditional task. The impairment exhibited by monkeys with lesions of the NBM alone ameliorated with time but that following NBM+VDB lesions did not. Previous experiments have shown that monkeys with immunotoxic lesions of the VDB alone are impaired at learning visuospatial conditional discriminations but are unimpaired at learning simple visual discriminations. When monkeys with NBM lesions were given excitotoxic lesions of the CA1 field of the hippocampus the learning impairment on discriminations between objects which differed in few attributes was reinstated. Pretreatment with a cholinergic agonist improved learning ability on visual discrimination learning in all monkeys but this improvement was significantly greater in monkeys with lesions of the NBM. On conditional discrimination learning, which is particularly sensitive to hippocampal damage, pilocarpine produced a significant improvement in monkeys with NBM+VDB lesions (where the hippocampal dysfunction was cholinergic) but not in monkeys with NBM+CA1 lesions (where the hippocampal damage was structural).

Acetylcholine↗
PubMed1998

Characterisation, utilisation and clinical relevance of isolated perfused heart models of ischaemia-induced ventricular fibrillation.

The isolated perfused heart has been used increasingly during the last decade as a model for identifying actions of drugs on ventricular fibrillation (VF) induced by myocardial ischaemia. In addition, it has been used to explore the mechanisms responsible for the initiation and maintenance of VF, the concept of endogenous myocardial protection and the phenomenon of preconditioning. This article is a review of the available data (effects of drugs, sources of variation, comparison with other models and man, etc.) and an attempt to evaluate the possible clinical relevance. For several reasons, it is not possible to make a precise judgement on the absolute value of the model in terms of its ability to accurately predict the effectiveness of drugs in the prevention of sudden cardiac death, the main reason being the lack of a positive control, i.e. a drug with proven effectiveness against sudden cardiac death caused by VF in man. Nevertheless, the means by which one may reliably and reproducibly generate ischaemia-induced VF in different isolated heart preparations, and the factors (such as species, heart rate, perfusion constituents and involved zone size) that determine the incidence of VF are now well documented. Careful selection of species and experimental conditions permits the isolated heart of smaller inexpensive animals to function as a first line model for detecting anti-VF activity of probable relevance to phase 1 arrhythmogenesis (i.e., arrhythmogenesis during the first 30 min of ischaemia). In view of the absence of a clinical template from which to evaluate how well it predicts drug effectiveness in man, this model's clinical relevance, like that of all other preparations and models, can yet be neither accepted nor dismissed. Recent publication patterns suggest an increasing use of the model. Therefore, recommendations are made to facilitate its effective use.

Animals↗
PubMed1998

Growth inhibitory factor and zinc affect neural cell cultures in a tissue specific manner.

Deficiency of neuronal growth inhibitory factor (GIF) and abnormalities in zinc homeostasis have been suggested to play a role in the neuropathogenesis of Alzheimer's disease. We report here that embryonic chick cerebral cell cultures zinc and copper containing GIF in the presence of marmoset hippocampal extract reduces significantly and concentration dependently mitochondrial succinate dehydrogenase activity (MTT) and cell mass. In contrast, no indications could be found that GIF affected neural retina cell cultures. Our results suggest that the observed effects of GIF are not elicited by zinc.

Animals↗
PubMed2001

Glial cell line-derived neurotrophic factor concentration dependently improves disability and motor activity in MPTP-treated common marmosets.

Glial cell line-derived neurotrophic factor (GDNF) has previously reduced motor deficits and preserved nigral dopamine neurones in rhesus monkeys with a unilateral MPTP-induced lesion of substantia nigra. We now report on the ability of GDNF to reverse motor deficits induced by parenteral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets resulting in bilateral degeneration of the nigrostriatal pathway. Prior to GDNF administration, all MPTP-treated animals showed akinesia or bradykinesia, rigidity, postural instability and tremor. Intraventricular injection of GDNF (10, 100 or 500 microg) at 9 and 13 weeks post MPTP treatment resulted in a concentration dependent improvement in locomotor activity and motor disability which became significant after administration of 100 and 500 microg of GDNF. The most prominent improvements were in alertness, checking movements, and posture. It is concluded that intraventricular GDNF administration improves bilateral Parkinsonian motor disability following MPTP treatment and this may reflect an action of GDNF on remaining nigral dopaminergic neurones.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2002

Binding properties of the novel, non-peptide CGRP receptor antagonist radioligand, [(3)H]BIBN4096BS.

BIBN4096BS [[R-(R,(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl] pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-Piperidinecarboxamide] is a selective calcitonin gene-related peptide (CGRP) receptor antagonist with a picomolar affinity to the CGRP receptor in human neuroblastoma SK-N-MC cells. Here, we describe the characterisation of the binding properties of the tritiated radioanalogue of BIBN4096BS in SK-N-MC cells as well as in marmoset tissue. [(3)H]BIBN4096BS showed reversible and saturable binding to SK-N-MC cells with a K(D) of 0.045 nM. In competition experiments, [3(H)]BIBN4096BS is concentration-dependently displaced from SK-N-MC cell membranes by BIBN4096BS as well as by the endogenous ligand CGRP and its analogues with the rank order of affinity BIBN4096BS>human alpha-CGRP=human beta-CGRP>[Cys(Et)(2,7)]human alpha-CGRP>adrenomedullin (high affinity site)=human alpha-CGRP-(8-37)=human beta-CGRP-(8-37)>calcitonin=amylin. In the marmoset cortex, saturable [(3)H]BIBN4096BS binding was observed with a K(D) of 0.077 nM. CGRP showed biphasic competition of [(3)H]BIBN4096BS binding, whilst BIBN4096BS monophasically displaced its radioanalogue with a K(i) of 0.099 nM. These data, using [(3)H]BIBN4096BS, confirm the high affinity of this novel antagonist for the primate CGRP receptor and demonstrate furthermore that this radioligand is a useful tool to study CGRP receptor pharmacology.

Animals↗
PubMed2002

Dopamine reuptake inhibition and failure to evoke dyskinesia in MPTP-treated primates.

Nonspecific monoamine reuptake inhibitors reverse motor abnormalities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets without evoking established dyskinesia. However, it is not known whether dopamine reuptake inhibition alone explains these actions or whether noradrenaline and/or serotonin reuptake blockade also contributes. L-DOPA (12.5 mg/kg, p.o.) rapidly reversed the baseline locomotor deficits and motor disabilities, but evoked dyskinesia (especially limb chorea) in MPTP-treated common marmosets primed to exhibit involuntary movements. In contrast, the selective dopamine reuptake inhibitor 1-(2-(bis-(4-fluorophenyl)-methoxy)ethyl)-4-(3-phenylpropyl) piperazine dihydrochloride (GBR 12909) reversed motor deficits in a dose-dependent manner but, unlike L-DOPA, did not evoke established dyskinesia in these animals. Therefore, inhibition of dopamine reuptake does not evoke established dyskinesia in MPTP-treated primates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

Motor effects of a dopamine stabilizer (GMC1111) in primate models of Parkinson and hemiparkinsonism.

The effects on motor behavior of a new potential dopamine stabilizer: 2-amino-6-(N,N-di-n-propylamino)thiazolo[4,5-f]indan (GMC1111) were investigated in common marmosets with 6-hydroxydopamine lesions within the median forebrain bundle (12 unilateral, 6 bilateral). GMC1111 was administered orally or subcutaneously (s.c.) to unilaterally 6-hydroxydopamine lesioned monkeys, either alone or together with s.c. injections of apomorphine (0.2 mg/kg) and the effect on rotational behavior was examined. GMC1111 (0.03-3.0 mg/kg) alone, orally or s.c., did not induce rotational behavior. When apomorphine and GMC1111 were injected simultaneously, rotations were nearly abolished in three monkeys with a baseline apomorphine-induced rotation rate below 13/min, whereas GMC1111 did not modify the rotations in three high-rotating animals (>17/min). Oral administration of GMC1111 (1.0 and 3.0 mg/kg) abolished the apomorphine-induced rotations in another six unilaterally dopamine-denervated monkeys, indicating a good oral bioavailability. A low dose of GMC1111 (0.3 mg/kg) administered s.c. to marmosets with bilateral nigrostriatal lesions produced a reduction of Parkinson symptoms of approximately the same degree as with levodopa/benserazide (15/3.75 mg/kg), while higher doses of GMC1111 were less effective. When levodopa/benserazide was administered together with various doses of GMC1111 (0.3-3.0 mg/kg), the levodopa-induced peak-dose dyskinesias were reduced with the highest dose of GMC1111 (3 mg/kg). Taken together, GMC1111 modifies dopaminergic activity in a normalizing direction. Parkinson symptoms, as well as levodopa-induced dyskinesias are both reduced. This suggests the arrival of another member of the new dopamine stabilizer family.

Animals↗
PubMed2003

Effect of JTT-705 on cholesteryl ester transfer protein and plasma lipid levels in normolipidemic animals.

This study evaluated JTT-705, S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate, as a cholesteryl ester transfer protein (CETP) inhibitor in several animal species. In vitro, JTT-705 inhibited plasma CETP activities of humans, rabbits, hamsters, cynomolgus monkeys and marmosets with IC(50) values of 5.5, 1.0, 11.7, 2.4 and 6.3 microM, respectively. The thiol form (JTP-25203) also inhibited those activities with IC(50) values of 2.8, 0.44, 0.52, 1.3 and 1.1 microM, respectively. Following oral administration to normolipidemic animals (rabbits, hamsters and marmosets), JTT-705 reduced plasma CETP activity, increased high density lipoprotein cholesterol (HDL-cholesterol), and decreased the ratio of non-HDL-cholesterol to HDL-cholesterol (atherogenic index) in all species. In marmosets, JTT-705 increased slow alpha-migrating lipoprotein (apolipoprotein E-rich HDL) in agarose gel electrophoresis, indicating that HDL metabolism in JTT-705-treated marmosets is similar to that in CETP-deficient humans. These results indicate that JTT-705 can be expected to inhibit plasma CETP activity and improve plasma lipoprotein profiles in a wide range of animal species, including humans.

Administration, Oral↗
PubMed2000

Species selectivity of a small molecule antagonist for the CCR1 chemokine receptor.

The species specificity of a small molecule antagonist for the human CCR1 chemokine receptor, 2-2-diphenyl-5-(4-chlorophenyl)piperidin-1-yl)valeronitrile (CCR1 antagonist 1), has been examined using cloned CCR1 receptors from various species. The compound was able to bind to rabbit, marmoset, and human CCR1, and was able to block the functional activation of these receptors. However, it failed to significantly displace radiolabeled macrophage inflammatory protein-1alpha (MIP-1alpha) binding to mouse CCR1 at concentrations up to 10 microM. These data suggested that the antagonist binding site is well-conserved in rabbit, marmoset and human CCR1, but not in mouse CCR1. The functional selectivity and mechanism of action for CCR1 antagonist 1 were further characterized. CCR1 antagonist 1 blocked the increase in intracellular Ca(2+) stimulated by CCR1 agonists, but had no effect on N-formyl-Met-Leu-Phe (FMLP), monocyte chemotactic protein-1 (MCP-1) and stromal-derived factor 1alpha (SDF1alpha)-induced Ca(2+) mobilization, demonstrating functional selectivity for CCR1. Since CCR1 antagonist 1 is a functional antagonist of marmoset and rabbit CCR1 receptors, it should be possible to test its efficacy in animal models of disease.

Amino Acid Sequence↗
PubMed1991

Horse and marmoset monkey sperm bind to the zona pellucida of salt-stored human oocytes.

The present study demonstrates that horse and marmoset monkey sperm can bind to the human zona of salt-stored oocytes that failed to fertilize in vitro. Marmoset monkey sperm are also able to penetrate the salt-stored human zona. In contrast, human sperm do not bind to the zona of either horse or marmoset monkey oocytes. These results suggest that human sperm binding to the zona pellucida is more strictly species-specific than it is for horse and marmoset monkey sperm. In contrast, horse and marmoset monkey sperm contain receptors recognized by the human zona.

Animals↗
PubMed1985

Characterization of spontaneous colitis in cotton-top tamarins (Saguinus oedipus) and its response to sulfasalazine.

Chronic colitis in the cotton-top tamarin (CTT) has been characterized by obtaining distal colonic biopsy specimens, hematocrits, serum albumins, and stools for bacteriologic and parasitic examination in nondebilitated living CTTs. The species specificity of the histologic features of colitis observed in the CTT was assessed by obtaining distal colonic biopsy specimens from 10 animals of other primate species for histologic examination. Histologic evidence of active colitis was found in 50% of adult CTTs but was absent in all non-CTT species studied. Forty-two stool samples obtained from 18 CTTs yielded only one isolate (Campylobacter). In addition to active colitis, CTT rectal mucosa also often had subtle irregularities in mucosal structure that were not present in nonrelated primate species and might represent chronic colitis. Metaplasia was not observed. The therapeutic effects of oral sulfasalazine (50 mg/kg X day) on CTT colitis were assessed in a randomized 10-wk placebo controlled crossover study. This study demonstrated significant improvement in disease activity as judged histologically (p less than 0.05) and significant increases in animal weight (p less than 0.01) and serum albumin (p less than 0.01) during sulfasalazine therapy when compared with saline control. Sulfasalazine therapy can ameliorate the effects of this disease and offers promise in maintaining experimental colonies of this endangered species for future studies.

Animals↗