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At least 1,531 records · Page 85Linked to original sources
PubMed1995

Structural dynamics of synapses and synaptic components.

Learning and memory formation are apparently based on cascades of molecular and cellular processes with increasing time constants (ms to days and weeks), but even the most long-lasting effects are transient. Memory traces may permanently modify the behavior (activity patterns, gene expression) of neurons and neuronal networks. Therefore the question is raised whether our current view on the stability of synapses under normal conditions is tenable. Evidence is reviewed suggesting that as direct or indirect effects of modifications in bioelectrical activity and chemical trophicity, synapses may be remodeled and removed within days and weeks, and possibly within hours. Accordingly, species-specific connectivity patterns are not restricted to the standard architecture of the CNS, but (morpho-)genetics allow for a considerable number of alternative wiring patterns, which appear under unusual conditions during ontogenesis and in adulthood. Our present knowledge suggests that, rather than the formation of synapses, they are a selective process. Until now there is no direct method of measuring either synaptic reorganization or the average life span of synapses. Specific cases, however, allow to estimate synapse turnover during ontogenesis, at its lowest possible level. Such data suggest that each synapse is on average remodeled or replaced several to many times during normal developmental, e.g. in the cerebral cortex of Marmoset monkeys at the very least 5 to 10 times (corresponding to 250 million synapses eliminated per hour in area 17!). It is discussed how the consequences of synapse turnover could be utilized by learning processes. Conclusions are followed by an outlook.

Animals↗
PubMed1996

Cognitive functions of the basal forebrain cholinergic system in monkeys: memory or attention?

The cholinergic hypothesis of memory dysfunction originally proposed that dysfunction of cholinergic neurons in the basal forebrain cholinergic system (BFCS) may be responsible for the memory deficits associated with aging and Alzheimer's disease (AD). This hypothesis directed focus on the BFCS in experimental animal models of AD. In contrast to numerous studies in rodents, fewer investigations have been conducted in monkeys with BFCS lesions. The medical septal nucleus/nucleus of the diagonal band of Broca (MS/NDBB) and the nucleus basalis of Meynert (NBM) may be involved in different cognitive functions in monkeys. Although few investigations have specifically addressed the issue of cognitive functions of the MS/NDBB in monkeys, there is some indication that these regions may be important for memory. In contrast, lesions of the NBM do not consistently disrupt mnemonic functions in monkeys. Recent electrophysiological and lesion studies of monkeys indicate that the NBM may play a more important role in attention functions, impairments of which are an early and significant feature of patients with AD.

Animals↗
PubMed1995

Binding of valsartan to mammalian angiotensin AT1 receptors.

The binding characteristics of the angiotensin AT1 receptor antagonist valsartan were investigated in different animal species and tissues. Using [125I](Sar1,Ile8) angiotensin II as radioligand, affinity constants were determined in liver and adrenal rat and marmoset, human adrenal and in rat aortic smooth muscle cells. In all tissues tested, valsartan had a greater affinity for the AT1 receptor than losartan (on average 5-fold). The affinities of both antagonists were up to 30 times weaker in the dog tissues [3H]Valsartan bound with high affinity (Kd 1.44 nmol/l) to the rat aortic smooth muscle cell AT1 receptor. Binding was saturable and reversible. Non-specific binding was low (10%). Reports that [3H]losartan binds to a non-angiotensin II binding site in rat liver and in other tissues could be confirmed. [3H]Valsartan on the other hand bound only to the AT1 receptor. Using a competition binding assay with [3H]losartan on rat liver membranes it could be shown that valsartan can bind to the 'losartan binding site', but at a 10,000-fold less affinity than for the AT1 receptor. Valsartan is therefore a highly specific and selective antagonist of the AT1 receptor. Due to its high affinity and low non-specific binding it is a suitable radioactive antagonist for the study of the distribution and function of the angiotensin AT1 receptor.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1995

L-DOPA reverses altered gene expression of substance P but not enkephalin in the caudate-putamen of common marmosets treated with MPTP.

The mRNA levels encoding neuropeptides were measured in the caudate nucleus, putamen and nucleus accumbens of common marmosets exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine pyridine (MPTP). Motor deficits induced by MPTP treatment were characterized by akinesia, postural abnormalities and rigidity. Seven days after MPTP treatment, there was a marked increase in levels of enkephalin mRNA in the caudate nucleus and putamen. In contrast, the hybridization signal for substance P mRNA was reduced. Alterations in the mRNA encoding neuropeptides were similar but less extensive in marmosets at 18-50 months following MPTP treatment. No significant changes in enkephalin or substance P mRNA in the nucleus accumbens were observed at either time. Treatment with L-DOPA plus carbidopa for 4 weeks reversed MPTP-induce motor deficits and other behavioural abnormalities. The decrease in substance P mRNA in the striatum of MPTP-treated animals was reversed by L-DOPA treatment and reached levels above those found in normal animals. In contrast, the increase in enkephalin mRNA in marmosets treated with MPTP was not altered by L-DOPA treatment. In the nucleus accumbens the levels of peptide mRNA were not affected by L-DOPA treatment. Loss of nigral dopamine cells in a primate species causes opposing alterations in the expression of enkephalin and substance P mRNA in the caudate nucleus and putamen. No changes were observed in the nucleus accumbens, which reflects the resistance of the mesolimbic neurons to MPTP toxicity. While the decrease in substance P mRNA was reversed by L-DOPA treatment, the increase in enkephalin mRNA was not. This may partly indicate the greater effect of L-DOPA on the direct GABA pathway compared to the indirect output pathway from the striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Molecular basis of virulence and growth of hepatitis A virus in cell culture.

The ability of engineering variants of hepatitis A virus (strain HM175) to replicate in cell culture or to cause disease in marmosets was evaluated. Virus variants were encoded by chimeric genomes constructed from infectious cDNA clones of two viruses (wild type and cell-culture-adapted) which differed in their ability to grow in vitro and to cause acute hepatitis in marmosets. Transfection and infectivity assays indicated that virus growth in vitro could be enhanced by subcloning the cell substrate prior to infection or by introducing multiple combinations of two or more mutations into the wild type genome. Various chimeric viruses induced liver enzyme elevations in marmosets, indicating that attenuation of virulence also required multiple mutations.

Animals↗
PubMed1993

Preparation and immunogenicity of an inactivated hepatitis A vaccine.

A hepatitis A vaccine was prepared by formaldehyde inactivation of purified hepatitis A virus (HAV) LSH/S strain grown on human diploid MRC-5 cells. The vaccine was devoid of residual infectivity in vitro and failed to induce in marmoset monkeys any pathological features or variations of haematological and clinical chemistry values. Infectious HAV particles were not detected in faeces and sera of the vaccinated primates by ELISA or after passages in MRC-5 cells. The immunogenicity of the vaccine was evaluated by injecting guinea-pigs with 0.8, 0.2 or 0.05 micrograms of HAV antigen adsorbed onto 0.5 and 1 mg of Al (OH)3 or 0.3 mg of AlPO4. The antibody response, measured by a competitive radioimmunoassay, was dose- and adjuvant-dependent. One injection of 0.2 micrograms of AlPO4-adsorbed HAV antigen induced seroconversion in 100% of animals and high levels of specific and neutralizing serum antibodies. A further increase of antibody titres was observed after the second and third inoculations. These results show that this vaccine formulation is safe and immunogenic in animal models, and suggest that it should be evaluated further by human clinical studies.

Adjuvants, Immunologic↗
PubMed1996

Comparison of the efficacy of single or repeated HI-6 treatment following soman poisoning in guinea pigs and marmoset monkeys.

The therapeutic efficacy of single or repeated doses of HI-6, together with atropine, against soman poisoning were compared both in guinea pigs and in marmoset monkeys. In addition, the pharmacokinetics of HI-6 were determined after single or repeated injections. Both single and repeated HI-6 injections protected guinea pigs effectively against 2 x LD50 soman. The plasma levels of HI-6 after single HI-6 injection fitted a one-compartment elimination model. The plasma levels of HI-6 following repeated injections were in accordance with those predicted using the data obtained after single HI-6 injection. No evidence was found for any disturbance of the HI-6 elimination in guinea pigs following soman intoxication. Marmosets were intoxicated with 2 x LD50 soman (s.c.), followed after 1 min by i.m. injections of atropine and HI-6. One and 2 h later, four animals received additional HI-6 injections. The pharmacokinetics of HI-6 in plasma, after single and repeated HI-6 injections were similar to those found in the guinea pig. Furthermore, repeated HI-6 injections protected effectively against soman: four out of four animals survived, in fair condition. In contrast, only one out of four animals receiving single HI-6-treatment fully recovered within a few days. Two animals died, the fourth animal survived, but had to be euthanized 3 weeks after intoxication.

Animals↗
PubMed1984

Identification of different subpopulations of neostriatal neurones projecting to globus pallidus or substantia nigra in the monkey: a retrograde fluorescence double-labelling study.

Fluorescent tracers (Nuclear Yellow, True Blue, Fast Blue) were injected, in various combinations, into the globus pallidus and substantia nigra in three marmosets. Examination of perikarya in the ipsilateral neostriatum, well removed from pallidal injection sites, revealed that the predominant pattern was of single-labelled cells, retrogradely labelled from either the globus pallidus or substantia nigra. It is suggested, on the basis of this evidence and data previously available, that the striatum contains at least three types of efferent neurones, one projecting exclusively to the globus pallidus, one projecting exclusively to the substantia nigra, and another projecting to both structures.

Animals↗
PubMed1986

The dopamine neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces histological lesions in the hypothalamus of the common marmoset.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to marmosets resulted in parkinsonism and degeneration of the substantia nigra pars compacta. Examination of the hypothalamus showed neuronophagic-like rosettes of glial cells and diffuse increase in glial numbers in areas of the dopaminergic A11-A14 groups. These findings suggest that MPTP may be toxic to dopamine neurons of the hypothalamus as well as to the substantia nigra.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

The D1 agonist SKF 38393 inhibits the antiparkinsonian activity of the D2 agonist LY 171555 in the MPTP-treated marmoset.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced persistent motor deficits. Administration of the D1 agonist SKF 38393 (2.5-20 mg/kg, i.p.) caused a dose-dependent increase of this akinesia. Administration of the D2 agonist LY 171555 (0.3 mg/kg, i.p.) reversed the motor deficits induced by MPTP treatment. Pretreatment of animals with SKF 38393 (2.5-20 mg/kg, i.p.) caused dose-dependent inhibition of the anti-parkinsonian action of LY 171555 (0.3 mg/kg i.p.). In primates SKF 38393 does not reverse motor deficits induced by MPTP and inhibits the actions of a D2-agonist.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Dopamine D1 and D2 receptor interactions in the MPTP-treated marmoset.

In a modified MPTP model of Parkinson's disease in the marmoset, both L-DOPA and the dopamine D2 agonist quinpirole were found to exhibit anti-bradykinetic activity. Both the dopamine D1 agonist SKF38393 and the D1 antagonist SCH23390 reduced the anti-bradykinetic action of L-DOPA and quinpirole. These results are discussed with respect to partial agonist activity of SKF38393 and the possibility that other dopamine receptors may be required for anti-Parkinsonian drug activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Effects of bifemelane on parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset.

The effects of bifemelane on parkinsonism were shown in MPTP-treated common marmosets. The administration of bifemelane increased locomotor activity in MPTP-treated marmosets but not in normal control marmosets. In a microdialysis study, extracellular levels of dopamine and its metabolites increased following the administration of bifemelane. These results indicate that it is worth studying the effects of bifemelane hydrochloride on patients with Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1979

Chondroitin sulfates of the epiphysial cartilages of different mammals.

1. The distribution chondroitin 4- and 6-sulfates in the epiphysial cartilages of several mammals are reported. 2. Chondroitin 6-sulfate is present in higher relative proportion in articular surfaces of young and adult epiphysial cartilages in most of the mammals studied. 3. Exception to this was found in some species of the order Rodentia in which chondroitin 4-sulfate was almost the only chondroitin present in young and adult cartilages. 4. These and other results suggest that chondroitin 4-sulfate may be an important component for the calcification process, whereas chondroitin 6-sulfate seems to be related to the integrity of the articular surfaces.

Aging↗
PubMed1993

Differences in levels of erythrocyte glutathione and its metabolizing enzyme activities among primates.

1. The levels of erythrocyte glutathione and the activities of its metabolizing enzymes--glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and glutathione reductase (GR)--were measured in four species of primates: human, rhesus monkey, common marmoset and common tree shrew. 2. There were marked differences in GSH-Px and GST activities among the primates, while GR activity and glutathione level were much less variable.

Animals↗
PubMed1982

The distribution and some morphological features of substantia nigra neurons that project to the thalamus, superior colliculus and pedunculopontine nucleus in the monkey.

Neurons of the substantia nigra's pars reticulata that send axons to the thalamus, superior colliculus and midbrain reticular formation (including the pedunculopontine nucleus) have been revealed in monkeys by the technique of retrograde transport of horseradish peroxidase. The populations of nigrothalamic, nigrotectal and nigroreticular neurons differ from one another in their number, intranigral distribution and somatodendritic size and shape. Nigrothalamic cells are the most abundant and, although scattered throughout the mediolateral expanse of the pars reticulata, their numbers progressively diminish from rostral to caudal levels. Nigrotectal cells are least numerous and are restricted almost exclusively to the lateral margin of the rostral one-half of the pars reticulata. Nigroreticular cells, like nigrothalamic, are scattered throughout the mediolateral dimension of the nucleus, but are more commonly located at middle to caudal levels. In addition to their restricted intranigral location, the nigrotectal cells are larger, polygonal and have more major dendritic processes than the smaller nigrothalamic and nigroreticular cells which are usually triangular or fusiform. A small proportion of cells of all three types appears to project contralaterally. These findings indicate that the efferent organization of the primate pars reticulata differs markedly from that of the rodent and the monkey's nigrotectal cells constitute a spatially and morphologically distinct subpopulation within the pars reticulata. These data should be useful in understanding the functional organization of topographic inputs to the pars reticulata such as that from the neostriatum.

Animals↗