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

Using a monoclonal antibody that recognizes specifically a high polysialylated form of N-CAM (high PSA N-CAM), the temporal and spatial expression of this molecule was studied in developing spinal cord and neural crest derivatives of mouse truncal region. Temporal expression was analyzed on immunoblots of spinal cord and dorsal root ganglia (DRGs) extracts microdissected at different developmental stages. Analysis of the ratio of high PSA N-CAM to total N-CAM indicated that sialylation and desialylation are independently regulated from the expression of polypeptide chains of N-CAM. Motoneurons, dorsal root ganglia cells and commissural neurons present a homogeneous distribution of high PSA N-CAMs on both their cell bodies and their neurites. Sialylation of N-CAM can occur in neurons after their aggregation in peripheral ganglia as demonstrated for dorsal root ganglia at E12. Furthermore, peripheral ganglia express different levels of high PSA N-CAM. With in vitro models using mouse neural crest cells, we found that expression of high PSA N-CAM was restricted to cells presenting an early neuronal phenotype, suggesting a common regulation for the expression of high PSA N-CAM molecules, neurofilament proteins and sodium channels. Using perturbation experiments with endoneuraminidase, we confirmed that high PSA N-CAM molecules are involved in fasciculation and neuritic growth when neurons derived from neural crest grow on collagen substrata. However, we demonstrated that these two parameters do not appear to depend on high PSA N-CAM molecules when cells were grown on a fibronectin substratum, indicating the existence of a hierarchy among adhesion molecules.
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PMID:Analysis of high PSA N-CAM expression during mammalian spinal cord and peripheral nervous system development. 176 42

Polysialic acid, or PSA, is a term used to refer to linear homopolymers of alpha(2,8)-sialic acid residues displayed at the surface of some mammalian cells. PSA is typically linked to the neural cell adhesion molecule N-CAM, where it can modulate the homotypic adhesive properties of this polypeptide. PSA expression is developmentally regulated, presumably through mechanisms involving regulated expression of sialyltransferases involved in PSA biosynthesis. Several different sialytransferase sequences have been implicated in PSA expression, although the precise roles of these enzymes in this context remain unclear. One such sequence, termed STX, maintains approximately 59% amino acid sequence identity with another sialyltransferase (PST-1, from hamster; PST, human) that is known to participate in PSA expression. While a murine STX fusion protein can catalyze the synthesis of a single alpha(2,8)-sialic acid linkage in vitro, the ability of STX to participate in PSA expression in vivo has not been demonstrated. We show here that STX transcripts are present in a PSA-positive, N-CAM-positive human small cell carcinoma line (NCI-H69/F3), but are absent in a variant of this line (NCI-H69/E2) selected to be PSA-negative and N-CAM-positive. To functionally confirm this correlation, we have cloned a human cDNA encoding the human STX sequence, and show, by transfection studies, that human STX can restore PSA expression when expressed in the PSA-negative, N-CAM-positive small cell carcinoma variant. We furthermore show that STX can confer PSA expression when expressed in a PSA-negative, N-CAM-positive murine cell line (NIH-3T3 cells), or when expressed in PSA-negative, N-CAM-negative COS-7 cells. These observations imply that STX, like PST-1/PST, can determine PSA expression in vivo. When considered together with the correlation between STX expression and PSA expression in vivo in the brain, these results suggest a regulatory role for STX in PSA expression in the developing central nervous system and small cell lung carcinoma.
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PMID:A human STX cDNA confers polysialic acid expression in mammalian cells. 755 89

Polysialylated neuronal cell adhesion molecule (PSA-N-CAM) is a cell surface molecule associated with neurons that undergo changes in configuration or spatial translocation. In both cases, this molecule is thought to reduce the adhesivity of these cells or of their processes, which can thereby insinuate themselves into the existing parenchyma. We used a monoclonal antibody specific to PSA to offer what we believe is the first account of the distribution of PSA-N-CAM in the adult songbird brain. This antibody stained a diversity of cell classes and processes, as follows: 1) a subset of ventricular zone cells; 2) migrating cells thought to be neuroblasts; 3) a subset of differentiated neurons; 4) some brain surface astrocytes; 5) some tanycytes; 6) the neuropil of some regions; 7) some axonal fibers; and 8) possibly some synapses. Our results demonstrate also, for the first time, the wide distribution of a very numerous population of migrating cells in the telencephalon and the seasonal regulation of PSA-N-CAM expression in a part of the adult brain known to undergo seasonal changes in cell recruitment and function. However, we did not find PSA-N-CAM associated with young migrating cells in the high vocal center (HVC), nor was there PSA-N-CAM in the robust nucleus of the archistriatum (RA), which is known to receive new axonal endings from HVC. In these instances spatial translocation may occur with the assistance of other surface molecules.
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PMID:Expression of polysialylated N-CAM in the central nervous system of adult canaries and its possible relation to function. 756 Feb 71

The regulated expression of neural cell adhesion molecule (NCAM) isoforms in the brain is critical for many neurodevelopmental processes including neurulation, axonal outgrowth, and the establishment of neuronal connectivity. We have investigated the expression of the major adult isoforms of NCAM (NCAM-180, NCAM-140, and NCAM-120) and its embryonic highly polysialylated isoform (PSA-NCAM) in the hippocampal region of postmortem brains from 10 schizophrenic and 11 control individuals. Immunohistochemical analysis with a monoclonal antibody recognizing the PSA-NCAM revealed immunoreactivity primarily in the dentate gyrus and in a subset of cells in the hilus region. We have observed a 20-95% reduction in the number of hilar PSA-NCAM-immunoreactive cells in the great majority of schizophrenic brains. The change in PSA-NCAM immunoreactivity is not obvious in other hippocampal subfields. Western blots of tissues from the hippocampal region (as well as from the frontal cortex) probed with a polyclonal antibody recognizing all NCAM isoforms did not reveal significant changes in the overall expression of NCAM, suggesting that the decrease in PSA-NCAM-immunoreactive cells may be related to post-translational processing of the molecule. The expression of this embryonic form of NCAM has been proposed to be related to synaptic rearrangement and plasticity. Therefore, the decrease in PSA-NCAM immunoreactivity in schizophrenic hippocampi may suggest an altered plasticity of this structure in a large proportion of schizophrenic brains. These findings may bear significance to the "neurodevelopmental hypothesis" of schizophrenia.
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PMID:Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brains. 770 24

In the brain of adult mice, cell division persists in the subventricular zone (SVZ) of the lateral ventricles. These SVZ cells migrate rostrally 3-5 mm to the olfactory bulb, where they differentiate into neurons. We have investigated the distribution of PSA-N-CAM in the adult mouse forebrain. Immunoreactivity for PSA-N-CAM precisely reveals the migratory pathway of SVZ cells. This pathway of PSA-N-CAM positive cells starts in the lateral wall of the lateral ventricle, where immunopositive cells form weblike patterns. The PSA-N-CAM positive pathway extends rostrally between the corpus callosum and the striatum into the anterior ventral telencephalon, and then into the core of the olfactory bulb. Experiments in which [3H]-thymidine was injected systemically indicated that the majority of the dividing cells on the SVZ of the lateral ventricle and along the migratory pathway are positive to PSA-N-CAM or closely associated with PSA-N-CAM. Microinjection of [3H]-thymidine into the SVZ of the lateral ventricle to label a small patch of dividing SVZ cells shows that neuroblasts that migrated away from the injection site are positive or are closely associated with other cells that are positive for PSA-N-CAM. Migrating cells are tethered together, forming long chains of immunopositive cells. The migratory pathway is formed by 30-40 of these immunopositive chains. Radially oriented individual PSA-N-CAM positive cells were observed in the olfactory bulb. These cells seem to have broken away from chains of immunopositive cells in the core of the olfactory bulb and to be migrating to more superficial layers. Little is known about the mechanisms of tangential migration during development and in adulthood. The cell-cell arrangement revealed by PSA-N-CAM staining suggests new models for this form of neuronal migration. PSA-N-CAM localization along the migratory pathway to the olfactory bulb suggests that in the adult brain this molecule plays a role in migration of neuronal precursors.
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PMID:Embryonic (PSA) N-CAM reveals chains of migrating neuroblasts between the lateral ventricle and the olfactory bulb of adult mice. 789 39

By combining both immunocytochemical and functional investigations, a hypothetical framework will be developed for the molecular mechanisms underlying neuron-glia interactions during development and regeneration of peripheral nerves. In particular, the immunoglobulin-like molecules L1, N-CAM, MAG and P0, the extracellular matrix molecules laminin and tenascin, and the carbohydrates PSA and L2/HNK-1 will be considered. During early stages of limb bud innervation in embryos, L1 and N-CAM are expressed on axons and Schwann cells and are involved in axonal fasciculation, whereas tenascin is thought to be involved in forming a scaffold around the nerve possibly preventing axons and/or Schwann cells from leaving the nerve. PSA has been shown to be involved in pathway selection at initial stages of limb bud innervation. Later on, when motor axons enter muscles, the carbohydrates determine the branching pattern of the nerves. During myelination, L1 appears to play a pivotal role during the formation of the first Schwann cell loops around the prospective myelin-containing axons. MAG and P0 appear also to be functionally involved at initial stages of myelin formation. Additionally, MAG may contribute to the formation and maintenance of non-compacted myelin and axon-Schwann cell apposition whereas P0 is involved in myelin compaction. Under regenerative conditions, L1, N-CAM, laminin, and tenascin are strongly up-regulated by denervated Schwann cells. In vitro observations strongly suggest that these molecules might foster axonal regeneration. The carbohydrate PSA is confined to regrowing axons and is also a candidate to support axonal regrowth. L2/HNK-1, which is found on motor axon-associated Schwann cells, may provide regenerating motor axons with a selective advantage over others resulting in appropriate reinnervation of motor pathways. Since many of the functional studies this review refers to have been performed in vitro, some of the conclusions drawn need reexamination in vivo. Gene manipulations, such as the generation of null mutants followed by a thorough morphological and immunocytochemical investigation may be a powerful tool to resolve this problem.
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PMID:Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves. 817 15

The presence of the neural cell adhesion molecule, NCAM, is indicative for a poor prognosis in lung-cancer patients. Using MAb 735, we have investigated the expression of polysialic acid, PSA, on NCAM in a spectrum of neuro-endocrine lung tumors, ranging from the slowly growing typical carcinoids via the atypical carcinoids with clinically unpredictable behavior to the highly aggressive small-cell lung carcinomas. Our immunohistochemical findings indicate a significant association between the presence of PSA on the tumor cells and an aggressive and immature sub-type of the tumor. This might be related to impairment of cell-cell and cell-matrix interactions by the presence of PSA, as we demonstrated in vitro, since detachment is one of the first steps in the metastatic process. The NCAM-MAb 123C3 used in these studies appeared extremely useful in immunoscintigraphy and immunotherapy of SCLC xenografts in nude mice, and for immunoscintigraphy of a SCLC patient. This may be explained by internalization of the 123C3 antibody, which we demonstrated in vitro. 123C3 is the only Cluster-I SCLC MAb studied thus far that becomes internalized.
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PMID:NCAM and lung cancer. 819 95

The patterns of expression of polysialylated ("embryonic") form of Neural Cell Adhesion Molecule (PSA/E-N-CAM) and of all N-CAM isoforms were investigated by indirect immunofluorescence and immunoblotting during the development of the Central Nervous System (CNS) and during the regeneration of the caudal Spinal Cord (SC) of the amphibian urodeles Pleurodeles waltl (Pw) and Notophthalmus viridescens (Nv). In this study, a monoclonal antibody to group B Meningococcus (anti-Men-B) which recognizes alpha-2,8-linked sialic units of PSA-N-CAM, and polyclonal anti-total N-CAM antibodies were used. Total-N-CAM immunoreactivities were consistently detected throughout the CNS of developing and adult newts. PSA-N-CAM expression predominated in "embryonic" developing CNS and was reduced to certain CNS areas in the adult urodeles. In the case of SC, the expression level of this isoform of N-CAM dramatically decreased to become low and nearly restricted to some ependymoglial cell surfaces. Interestingly, during newt tail regeneration, PSA-N-CAM was intensely reexpressed in regenerating SC, at the surface of ependymoglial cell processes and in axonal compartments. Expression was maximal at 4 to 6 weeks following amputation, and then gradually returned to a normal adult low level in well differentiated SC. These findings strongly supported the view that the expression of PSA-N-CAM was associated with the properties of plasticity shown by the SC ependymoglial tissue in newts, during tail regeneration. On the other hand, the high level of PSA-N-CAM expression in axonal compartments of regenerating as well as developing SC suggested that these isoforms of N-CAM could be implicated in axonal outgrowth within the "tunnels" defined by the radial ependymoglial processes. This transient PSA-N-CAM expression could therefore be considered both as a negative modulator of cell-cell and cell-substrate interactions and as a permissive factor for neuron differentiation.
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PMID:Expression of polysialylated neural cell adhesion molecule (PSA-N-CAM) in developing, adult and regenerating caudal spinal cord of the urodele amphibians. 839 80

To gain insight into the possible molecular mechanisms underlying axonal regeneration of neurons of the adult central nervous system (CNS), we have investigated, by in situ hybridization and by immunocytochemistry, the localization and sites of synthesis of the neurite outgrowth-promoting cell surface molecules L1, N-CAM and its highly sialylated form, N-CAM-PSA, in and around peripheral nerve grafts implanted into the thalamus of adult rats. Normal unoperated adult rat thalamus contains N-CAM and L1 but no N-CAM-PSA immunoreactive axons. Between 7 days and 13 weeks after graft implantation, L1, N-CAM and N-CAM-PSA were all present at the surface of axonal sprouts in the brain parenchyma close to grafts and in the central parts of Schwann cell columns within grafts. Schwann cell membranes were L1 and N-CAM positive at all postgraft survival times, more strongly at 2-4 weeks than other times, but were associated with N-CAM-PSA reaction product only where they abutted N-CAM-PSA positive axons. Schwann cell membranes apposed to basal laminae (which were avoided by regenerating CNS axons) were L1, N-CAM and N-CAM-PSA negative. Between 3 days and 8 weeks after grafting, N-CAM and L1 mRNA were generally weakly upregulated in neurons of the ipsilateral thalamus, but, most conspicuously, L1 mRNA was strongly upregulated in the neurons of the thalamic reticular nucleus; these neurons are known to regenerate axons very effectively into peripheral nerve grafts and are the probable source of most of the axons which enter thalamic grafts. N-CAM and L1 mRNA were also strongly upregulated in presumptive Schwann cells in the graft. These results show that regenerating CNS axons (re)express N-CAM-PSA and upregulate L1 and N-CAM, suggesting that all of these molecules may play a role in cellular interactions during the regeneration of CNS axons. Furthermore L1 synthesis appears to be particularly well correlated with the ability of CNS neurons to regenerate axons into peripheral nerve grafts.
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PMID:Molecular basis of interactions between regenerating adult rat thalamic axons and Schwann cells in peripheral nerve grafts I. Neural cell adhesion molecules. 854 58

Luteinizing hormone-releasing hormone (LHRH) neurons originate in the olfactory placode and vomeronasal organ and migrate to the brain from embryonic day 14 (E14) in the rat. We investigated the development of the vomeronasal nerve and its role as a guide for migrating LHRH neurons. Using fluorescent, lipophilic dye tracing methods, we observed axons that emerge from the vomeronasal organ and cross the nasal septum as several large fascicles. At E14-15, these fascicles converge as they enter the region of the cribriform plate and subsequently disperse, projecting dorsally and caudally across the olfactory bulb and rostral forebrain. At E16, the dorsal branch of the vomeronasal nerve forms a more tightly fasciculated projection; the caudal fibers remain dispersed, extending along the medial forebrain. The number of caudally directed axons decreases during development, leaving four or five present at postnatal day 4 (P4). Immunohistochemical studies indicate that the vomeronasal nerve can be divided into four spatially distinct subpopulations of fibers. One subset, composed of caudal fibers that terminate in the lamina terminalis, selectively expresses TAG-1, a transient axonal surface glycoprotein and PSA-N-CAM, a highly polysialated form of neural cell adhesion molecule. The extension and subsequent retraction of this branch of the vomeronasal nerve corresponds spatially and temporally with the migration of LHRH neurons from the nasal cavity to the brain. Our studies show that between E14 and E18, LHRH neurons migrate in contact with the TAG-1+, PSA-N-CAM+ caudal branch of the vomeronasal nerve.
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PMID:The migration of luteinizing hormone-releasing hormone neurons in the developing rat is associated with a transient, caudal projection of the vomeronasal nerve. 861 18


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