UMLS:C1519176 - FACTA Search

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Query: UMLS:C1519176 (PSA)
5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proper structuring of neural connections in the hippocampus is mediated by cell adhesion molecules, membrane-linked proteins involved in cell recognition and stabilization of cytoarchitecture. Modulated expression of the neural cell adhesion molecule (NCAM) at the synapse permits plasticity required for both learning and memory. Polysialylation of NCAM, particularly the synapse-specific 180 kDa isoform (NCAM180), allows hippocampal neurons to alter their neuronal connections during learning acquisition and memory consolidation in mature brain. These activity-dependent changes in NCAM expression represent a sensitive target for neurotoxicity. Trimethyltin (TMT), a potent hippocampal neurotoxicant, alters total NCAM expression in whole mouse hippocampus and impairs learning in rodents. To investigate the expression of polysialylated NCAM following TMT administration, Swiss-Webster mice were injected (i.p.) with 2.0 or 3.0 mg TMT/kg and sacrificed 6 hrs to 7 days later. Immunocytochemical staining for polysialylated NCAM (PSA-NCAM) revealed marked reduction of staining of hippocampal dentate granule cells 6-72 hours after TMT treatment. Partial recovery of hippocampal polysialylated NCAM was observed after 7 days. Immunoblot data indicated that loss of PSA-NCAM expression paralleled reductions seen in NCAM180 and markers of cytoskeletal integrity. Assays for proteolytic activity in hippocampus revealed rapid, reversible protease activation which correlated temporally with the reduction of NCAM180 and PSA-NCAM. Proteolytic degradation following hippocampal injury may serve to disrupt NCAM-mediated adhesion. Protracted loss of polysialylated NCAM in dentate gyrus following injury may serve as a useful marker in toxicant-induced learning disorders.
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PMID:Altered expression of polysialylated NCAM in mouse hippocampus following trimethyltin administration. 933 13

Cell adhesion molecules (CAMs) play a role in the normal development and regeneration of tissues as well as in the biological behaviour of tumors. We studied the immunohistochemical expression of various CAMs, such as neural cell adhesion molecule (NCAM), its polysialylated isoform (PSA-NCAM), epithelial (E-) cadherin, and beta1 integrins (alpha2beta1, alpha5beta1, alpha6beta1) in a series of frozen specimens of 10 normal nerves, 5 axonal neuropathies, 26 benign Schwannomas and 2 malignant peripheral nerve sheath tumors (MNST). NCAM was expressed by non-myelinating Schwann cells from normal nerves and overexpressed by Schwann cells from patients with chronic axonal neuropathies and Schwannomas. The expression was lower in MNST. Expression of PSA-NCAM was heterogeneously displayed by Schwann cells from the various tissues studied. Anti E-cadherin immunoreactivity was present in myelin sheath in normal nerves and axonopathies. It was expressed in some Schwannomas especially in vestibular Schwannomas. Integrins VLA alpha2 and VLA alpha6 were widely expressed by Schwann cells from normal nerves, axonal neuropathies and Schwannomas but their expression was low in MNST. VLA alpha5 was not expressed by Schwann cells from normal nerve and Schwannomas but present in chronic axonal neuropathies and MNST. In addition VLA alpha6 was strongly expressed by perineurial cells. These data show that CAMs have a characteristic pattern of expression in normal nerve. Also, some CAMs are always expressed by Schwann cells but the expression of others differs in normal nerves versus axonopathies or tumors, suggesting a role of the microcellular environment in the regulation of CAM expression. Schwannomas have different pattern of expression than MNST.
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PMID:Expression of cell adhesion molecules in normal nerves, chronic axonal neuropathies and Schwann cell tumors. 934 66

Early in development, the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is expressed by growth cones, neuronal processes, and neuronal cell bodies. In rat striatum, PSA-NCAM expression becomes progressively restricted to pre- and postsynaptic membranes and is undetectable by postnatal day 25 (P25), i.e., after corticostriatal synaptogenesis. This study examined the effects of cortical lesions performed on P14, when the corticostriatal projection is already primarily unilateral and cortical inputs have not yet formed asymmetric synapses on striatal neurons. Rats were killed on P25, and PSA-NCAM expression was examined by immunoblotting and immunohistochemistry with light and electron microscopy. In contrast to the case in controls, PSA-NCAM expression was maintained in the striatum of lesioned pups. Ultrastructural studies showed that PSA-NCAM was present 1) in growth cone-like structures and neuronal processes and 2) in striatal neurons. Together with the presence of growth cones, the observation that the number of asymmetric synapses was unchanged in the denervated striatum suggests that axonal sprouting occurred in response to the lesion. This was confirmed by axonal labeling in the denervated striatum after injection of Fluoro-Ruby in the contralateral cortex. The data indicate that P14 cortical lesions affect PSA-NCAM expression in the developing striatum 1) by inducing a robust axonal plasticity resulting in the presence of immature presynaptic elements that contain PSA-NCAM and 2) by delaying the loss of PSA-NCAM expression in striatal neurons, suggesting that the lesion affects the time course of striatal maturation.
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PMID:Regulation of the polysialylated form of the neural cell adhesion molecule in the developing striatum: effects of cortical lesions. 941 23

Different reports demonstrated that reactive glial cells express increased amounts of adhesion and matrix molecules. Despite a wealth of information on the expression of these molecules during development and after lesion, very little is known of how this expression is regulated. In the present report we used Western blots and immunocytochemistry to investigate the expression of neural cell adhesion molecule (NCAM), fibronectin and tenascin-C in cultured astrocytes from rat hippocampus. The effects of three different extracellular signals were analyzed: the glutamatergic receptor agonist kainic acid, the basic fibroblast growth factor (bFGF) and the bacterial lipopolysaccharide. Each treatment had a specific pattern of glial activation and differentially modified the expression of these proteins. Treatment of astrocytes with kainic acid resulted in an increase of tenascin-C, a decrease of fibronectin and a shift of NCAMs isoforms: NCAM 140 and PSA-NCAM (polysialic acid-rich NCAMs) were increased while NCAM 120 was decreased, bFGF increased fibronectin, tenascin-C and NCAM 120, while decreasing PSA-NCAM. Finally, the treatment of astrocytes with lipopolysaccharide induced a significant increase of fibronectin, tenascin-C and NCAM 120 but did not modify the expression of NCAM 140 and PSA-NCAM. These data suggest different mechanisms for modulation of cell surface interactions. They suggest that glial activation by bFGF and lipopolysaccharide are associated with an increase of the adhesive properties, while kainate action is rather associated with a decrease of the adhesiveness of astrocytes.
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PMID:Differential expression of fibronectin, tenascin-C and NCAMs in cultured hippocampal astrocytes activated by kainate, bacterial lipopolysaccharide or basic fibroblast growth factor. 943 29

The up- and downregulation of polysialic acid-neural cell adhesion molecule (PSA-NCAM) expression on motorneurons during development is associated respectively with target innervation and synaptogenesis, and is regulated at the level of PSA enzymatic biosynthesis involving specific polysialyltransferase activity. The purpose of this study has been to describe the cellular mechanisms by which that regulation might occur. It has been found that developmental regulation of PSA synthesis by ciliary ganglion motorneurons is not reflected in the levels of polysialyltransferase-1 (PST) or sialyltransferase-X (STX) mRNA. On the other hand, PSA synthesis in both the ciliary ganglion and the developing tectum appears to be coupled to the concentration of calcium in intracellular compartments. This study documents a calcium dependence of polysialyltransferase activity in a cell-free assay over the range of 0.1-1 mM, and a rapid sensitivity of new PSA synthesis, as measured in a pulse-chase analysis of tissue explants, to calcium ionophore perturbation of intracellular calcium levels. Moreover, the relevant calcium pool appears to be within a specific intracellular compartment that is sensitive to thapsigargin and does not directly reflect the level of cytosolic calcium. Perturbation of other major second messenger systems, such as cAMP and protein kinase-dependent pathways, did not affect polysialylation in the pulse chase analysis. These results suggest that the shuttling of calcium to different pools within the cell can result in the rapid regulation of PSA synthesis in developing tissues.
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PMID:Regulation of neural cell adhesion molecule polysialylation: evidence for nontranscriptional control and sensitivity to an intracellular pool of calcium. 949 Jul 30

Polysialylation of the neural cell adhesion molecule (NCAM) converts it into an anti-adhesive molecule, attenuating intercellular adhesion and repelling apposed membranes. Previous studies have demonstrated that interaxonal repulsion, or defasciculation, induced by polysialylated NCAM (PSA-NCAM) expressed along outgrowing chick motor axons promotes intramuscular branching and facilitates differential guidance of segregating axonal populations. In the present study, we have examined the expression of PSA-NCAM in a developing mammalian motor system during axonal outgrowth, separation of distinct axonal populations, and intramuscular branching. Furthermore, we provide the first clear demonstration of the spatiotemporal modulation of PSA-NCAM expression on myotubes during each stage of myogenesis. Immunohistochemical labelling was used to compare the spatiotemporal pattern of PSA-NCAM expression with those of total-NCAM, the cell adhesion molecule L1, and growth associated protein (GAP-43) during development of the phrenic nerve and diaphragm of fetal rats (embryonic days, E11-E19). During segregation of phrenic and brachial axonal populations at the brachial plexus (E12.5-E13), PSA-NCAM expression was restricted to phrenics, being absent from brachial motoneurons. Both populations labelled equivalently for NCAM, L1, and GAP-43. We postulate that PSA-NCAM may be a component of the molecular machinery that specifically guides phrenic motoneuron growth at the brachial plexus. During diaphragmatic morphogenesis, PSA-NCAM expression: (i) remained high within the phrenic nerve throughout intramuscular branching; (ii) was transiently up-regulated on myotubes during myotube separation associated with primary and secondary myogenesis; (iii) was restricted to those regions of primary and secondary myotube membranes, which were juxtaposed and about to separate. These data suggest a role for PSA-NCAM in the guidance of specific subsets of mammalian motoneurons and in intramuscular branching, and demonstrate an intimate correlation between PSA-NCAM expression and myotube separation.
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PMID:Polysialylated NCAM expression during motor axon outgrowth and myogenesis in the fetal rat. 949 1

1. The adult hypothalamoneurohypophysial system (HNS) undergoes reversible morphological changes in response to physiological stimulation. 2. In the hypothalamus, stimulation of neurohormone secretion results in reduced astrocytic coverage of oxytocinergic somata and dendrites so that their surfaces become directly juxtaposed. Concurrently, there is a significant increase in the number of GABAergic, glutamatergic. and noradrenergic synapses impinging on the neurons. 3. In the neurohypophysis, stimulation induces retraction of pituicyte processes from the perivascular area and enlargement and multiplication of neurosecretory terminals. 4. These neuronal-glial and synaptic changes are reversible with cessation of stimulation, thus rendering the HNS an excellent model to study physiologically linked structural neuronal plasticity in the adult CNS. 5. We still do not know the cellular mechanisms and factors underlying such plasticity. Recent studies indicate, however, that the adult HNS expresses molecular characteristics normally associated with histogenesis and/or tissue reorganization in developing or regenerating neural systems. They include expression of cell adhesion molecules such as the highly sialylated isoform of the neural cell adhesion molecule, PSA-NCAM, and the glycoproteins, F3 and tenascin-C. 6. The expression of PSA-NCAM and tenascin-C does not show striking differences in terms of age, sex or physiological condition but that of F3 varies considerably with neurohypophysial stimulation. 7. We postulate that such molecular features allow magnocellular neurons and their glia to undergo neuronal-glial and synaptic plasticity throughout life, provided the proper stimulus intervenes. 8. Thus, in the hypothalamic nuclei, centrally released oxytocin acting in synergy with steroids can induce such plasticity, while adrenaline, acting through beta-adrenergic mechanisms, does so in the neurohypophysis.
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PMID:Factors governing activity-dependent structural plasticity of the hypothalamoneurohypophysial system. 953 94

To investigate the possible role of nitric oxide (NO) in adult neurogenesis and neuron-glial migration in the rostral migratory stream (RMS), we used a double-labeled immunofluorescence technique together with confocal laser scanning microscopy, and examined the localization of nitric oxide synthase (NOS), the highly polysialylated isoform of neural cell adhesion molecule (PSA-N-CAM), and the astroglial marker in brain, S100 protein (S100), throughout the length of the subependymal layer (SEL) to olfactory bulb (OB) pathway of the adult guinea pig forebrain. Blast-like, beaded, clustered immature cellular elements stained for PSA-N-CAM and those having a typical astrocytic phenotypes positive for S100 protein were densely interlaced throughout the entire length of the SEL. Some S100 positive ependymoglial cells (tanycytes) gave off their basal projections into the closely packed PSA-N-CAM immunopositive clusters in the rostral extension of the subependymal zone (SEZre). The SEL was devoid of NOS immunoreactivity. A dense network of punctate, fenestrated and radially oriented immature cellular elements positive both for NOS and PSA-N-CAM intermingled and overlapped in the inner part of the internal granular layer (IGr), whereas in the outer part, PSA-N-CAM expression gradually diminished and the cells shifted to mature bipolar, spherical or spindle-shaped granule cells with uniform cellular contours, which were exclusively immunopositive for NOS. Radially oriented astroglial phenotypes were intertwined with PSA-N-CAM neuronal clusters in the SEL, and were closely apposed to NOS neuronal elements in the IGr. In summary, these results showed a distinct separation of neurons and glia as revealed by PSA-N-CAM and S100 protein immunostaining, and an inverse spatio-temporal correlation of expression between PSA-N-CAM (immature neuroblasts) and NOS (mature neurons) in the adult guinea pig RMS.
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PMID:Expression of NOS, PSA-N-CAM and S100 protein in the granule cell migration pathway of the adult guinea pig forebrain. 959 89

Striatal development proceeds during a protracted postnatal period in rats. In the dorsolateral striatum, the number of asymmetric synapses, formed mostly by glutamatergic afferents innervating the dendritic spines of medium-sized striatal neurons, increases during the 3rd postnatal week and then rapidly declines before reaching adult levels. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which is widely expressed along neuronal membranes early in development, becomes progressively localized to synapses, and is no longer detectable in remaining synapses after synaptic pruning has occurred. Administration of MK-801, an antagonist of N-methyl-D-aspartate receptors, on day 20, either peripherally or locally into the striatum, decreases asymmetric synapse number by 30% and totally abolishes immunolabelling for PSA-NCAM in the dorsolateral striatum.
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PMID:A role for N-methyl-D-aspartate receptors in the regulation of synaptogenesis and expression of the polysialylated form of the neural cell adhesion molecule in the developing striatum. 969 Nov 99

We described a double-site enzyme-linked immunosorbent assay (ELISA) to measure polysialic acid neural cell adhesion molecule (PSA-NCAM) level in CSF. Immunocapture of PSA-bearing molecules is first effected by means of a monoclonal antibody (anti-MenB), directed against sialic acid polymers and adsorbed into plastic wells. Linked PSA-NCAM is then revealed by means of a second antibody, directed against an aminoacid sequence of NCAM and labelled with peroxydase. The lowest amount of PSA-NCAM detectable was estimated to be 0.11 microgram/l. This value was considered as the threshold for positivity. PSA-NCAM level was measured using this method in CSF from 29 patients with medulloblastoma. CSF had been collected at different times following tumor excision and stored at--80 degrees C. At the same times, cytological examination in CSF (medulloblastoma metastatic cells) and craniospinal imaging (tomographic scan or MRI) had been performed. PSA-NCAM was never detected in control CSF. For patients in remission, beyond the post-operative period of 1 or 2 months, 18 on 21 exhibited a PSA-NCAM level below the threshold value. For refractory patients, so classified according to the positivity of cytology and/or imaging, whatever the time after the tumor excision, PSA-NCAM was always positive (23/23), while either cytology or imaging were positive less frequently (16/23 for both). For relapses, PSA-NCAM was more frequently positive (6/7) than cytology and imaging (1/7 and 5/7, respectively). We concluded that PSA-NCAM positivity in CSF may be a reliable marker to detect the invasive or metastatic feature of medulloblastoma.
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PMID:[Polysialylated NCAM in CSF, a marker for invasive medulloblastoma]. 975 72

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