Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) appeared during the evolution of vertebrates as a new mechanism for regulation of cell interactions. This large and abundant glycoprotein can exert steric effects at the cell surface that lead to the attenuation of cell-cell bonds mediated not only by NCAM but also a variety of other adhesion receptors. PSA-NCAM expression changes both as a result of developmental programs and physiological inputs. This global modulation of cell-cell attachment has been shown to facilitate cell migration, axon pathfinding and targeting, and plastic changes in the embryonic and adult nervous system.
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PMID:Roles, regulation, and mechanism of polysialic acid function during neural development. 1152 92

Repair and functional recovery after brain injury critically depends on structural and functional plasticity of preserved neuronal networks. A striking feature of brain structures where tissue reorganization and plasticity occur is a strong expression of the polysialylated neural cell adhesion molecule (PSA-NCAM). An important role of this molecule in various aspects of neuronal and synaptic plasticity has been revealed by many studies. Recently, a new mechanism has been elucidated whereby PSA-NCAM may contribute to signalling mediated by the neurotrophic factor BDNF, thereby sensitizing neurons to this growth factor. This mechanism was shown to be important for activity-induced synaptic plasticity and for the survival and differentiation of cortical neurons. A cross-talk between these molecules may, thus, reveal a key factor for properties of structural plasticity and in particular could mediate the activity-dependent aspects of synaptic network remodeling. Animal models have been developed to assess the role of these molecules in functional recovery after lesions.
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PMID:The role of neural cell adhesion molecules in plasticity and repair. 1169 Jun 14

Here we show a dual role of N-methyl-d-aspartate receptor (NMDAR) activation in controlling polysialylated neural cell adhesion molecule (PSA-NCAM) dynamic expression in the dorsal vagal complex (DVC), a gateway for many primary afferent fibres. In this structure the overall expression of PSA-NCAM decreases during the first 2 weeks after birth to persist only at synapses in the adult. Electrical stimulation of the vagal afferents causes a rapid increase of PSA-NCAM expression both in vivo and in acute slices before postnatal day (P) 14 whereas a similar stimulation induces a decrease after P15. Inhibition of NMDAR activity in vitro completely prevented these changes. These regulations depend on calmodulin activation and cGMP production at all stages. By contrast, blockade of neuronal nitric oxide synthase (nNOS) prevented these changes only after P10 in agreement with its late expression in the DVC. The pivotal role of NMDAR is also supported by the observation that chronic blockade induces a dramatic decrease in PSA-NCAM expression.
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PMID:Dual effects of NMDA receptor activation on polysialylated neural cell adhesion molecule expression during brainstem postnatal development. 1170 48

Characterizing the mechanisms by which endogenous factors stimulate neurogenesis is of special interest in view of the possible implication of newly generated cells in hippocampal functions or disorders. The aim of this study was to determine whether serotonin (5-HT) and oestradiol (E2) act through a common pathway to increase cell proliferation in the adult dentate gyrus (DG). We also investigated the effects of long-lasting changes in oestrogen levels on cell proliferation. Combining ovariectomy with inhibition of 5-HT synthesis using p-chlorophenylalanine (PCPA) treatment produced approximately the same decreases in the number of bromodeoxyuridine (BrdU) and PSA-NCAM immunolabelled cells in the subgranular layer as ovariectomy alone. Administration of 5-hydroxytryptophan (5-HTP) restored cell proliferation primarily decreased by ovariectomy, whereas oestradiol was unable to reverse this change in ovariectomized rats treated with PCPA. These findings demonstrate that 5-HT mediates oestrogen stimulation of cell proliferation in adult dentate gyrus. However, increase in ovarian hormones during pregnancy has no effect on dentate cell proliferation. This finding suggests that concomitant changes in other factors, such as glucocorticoids, may counterbalance the positive regulation of cell proliferation by 5-HT and oestradiol. Finally, oestrogen may regulate structural plasticity by stimulating PSA-NCAM expression independently of neurogenesis, as shown for instance by the increases in the number of PSA-NCAM labelled cells in pregnants. As 5-HT and oestrogen are involved in mood disorders, our data suggest that the positive regulation of cell proliferation and neuroplasticity by these two factors may contribute to restore hippocampal connectivity in depressive patients.
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PMID:Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrus. 1172 3

Highly polysialylated neural cell adhesion molecule (PSA-NCAM) is transiently expressed specifically in newly generated cells, and is important for migration and neurite outgrowth. To investigate the effect of aging on the migration of neural stem cell (NSC) after brain ischemia, the spatiotemporal expressions of immunoreactive PSA-NCAM were examined at 4 h or 1, 3 or 7 days after 90 min of middle cerebral artery occlusion (MCAO) in the young-adult or aged rats. In the sham control brain, PSA-NCAM staining was slightly observed both in dorsal and ventral parts of subventricular zone (SVZ) in the aged brain, but only in the dorsal part of SVZ in the young brain. After transient MCAO, immunoreactivity for PSA-NCAM increased in the number and the intensity in SVZ ipsilateral to MCAO in the young-adult brains and became the peak at 1 day, while that was at 3 days in the aged brains. These findings suggest that PSA-NCAM was located in different spatial distribution in normal condition between young and old rats. PSA-NCAM was induced after ischemia, and the temporal expression was also different after transient MCAO between young and older rats.
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PMID:Temporal and spatial differences of PSA-NCAM expression between young-adult and aged rats in normal and ischemic brains. 1173 Jul 11

In order to analyze the regulatory sequences involved in the neuronal expression of aromatic L-amino acid decarboxylase (AADC), we have generated transgenic mice carrying the LacZ gene under the control of a 3.6-kb human aadc genomic fragment flanking the neuronal alternative first exon. A series of double labeling experiments were performed to compare the pattern of transgene expression to that of specific markers for catecholaminergic and serotonergic neurons. In the adult brain parenchyma, transgene expression was observed in the substantia nigra (SN), the ventral tegmental area (VTA) and the dorsal, medial and pontine raphe nuclei. A large degree of co-expression was observed with tyrosine-hydroxylase (TH) in the SN and VTA, and with serotonin (5-HT) in the dorsal raphe nucleus. Moreover, expression was observed in cells that were both TH- and 5-HT-negative, in particular in the ventral tegmental decussation and the dorsal tip of the VTA. Transgene expression was also observed in the walls of central cavities. Cells positive for both beta-gal and PSA-NCAM were localized in the ventral ependyma of the third and fourth ventricle, and of the central canal of the spinal cord, in what appears to be the adult floor plate. Transgene expressing, PSA-NCAM negative, cells located along the ventral midline of the spinal cord seemed to have migrated out of the ependyma. Our data thus reveal the complexity of aadc gene regulation. The present transgene provides a unique marker for monoaminergic nuclei induced by the isthmus and for the adult floor plate.
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PMID:Neuronal promoter of human aromatic L-amino acid decarboxylase gene directs transgene expression to the adult floor plate and aminergic nuclei induced by the isthmus. 1175 71

Elevated osmolality and pCO(2) have been shown to alter sialylation in a protein-specific manner. In Chinese hamster ovary (CHO)MT2-l-8 cells, tPA sialylation changed only slightly from 40 to 250 mm Hg pCO(2), whereas neural cell adhesion molecule polysialic acid (NCAM PSA) content decreased by up to 70% at 250 mm Hg pCO(2), pH 7.2. NCAM PSA content also decreased with increasing NaCl or NH(4)Cl concentration. This suggests that PSA content is a sensitive indicator of conditions that may alter glycosylation. Amino acids and their derivatives have been used to protect hybridoma and CHO cell growth under hyperosmotic stress. We examined the impact of osmoprotectants on NCAM PSA content in CHO MT2-1-8 cells under hyperosmolality (up to 545 mOsm/kg) and at 195 and 250 mm Hg pCO(2). NCAM PSA content at 545 mOsm/kg was at least two-fold greater in the presence of glycine betaine or L-proline compared to that without osmoprotectant. Surprisingly, in the presence of 20 mM glycine betaine, PSA levels were 50-60% of the control level for osmolalities ranging from 320 to 545 mOsm/kg. Thus, glycine betaine inhibits NCAM polysialylation at osmolalities below 435 mOsm/kg and is beneficial at higher osmolalities. In contrast to glycine betaine, L-proline increased PSA content by 25-120% relative to the unprotected culture at < or =545 mOsm/kg. The decrease in NCAM PSA levels of CHO MT2-1-8 cells cultured at 195 mm Hg pCO(2)-435 mOsm/kg was not mitigated by the presence of 25 mM glycine betaine, glycine, or L-threonine, even though all of these compounds enhanced cell growth. At 250 mm Hg pCO(2), all osmoprotectants tested (20 mM L-threonine, L-proline, glycine, or glycine betaine) increased NCAM polysialylation, with 20 mM glycine betaine restoring NCAM PSA to near control levels. Thus, osmoprotectants may (partially) offset changes in glycosylation, as well as the inhibition of growth, in cells under environmental stress. Supernatant beta-galactosidase levels, which increase upon alkalization of acidic organelles, did not differ significantly under elevated pCO(2) and hyperosmolality from that at control conditions.
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PMID:Effects of osmoprotectant compounds on NCAM polysialylation under hyperosmotic stress and elevated pCO(2). 1178 9

In order to investigate the role of postnatal neurogenesis in granule cell number control in the rat dentate gyrus, we administered Methylazoxymethanol (MAM), a drug able to prevent cells from dividing, on P3, P5, P7, P9, when the most granule cells are produced. The effect of MAM on the number of proliferating precursors and of granule cells was examined at P16 and P90. We used 5-bromo-2'-deoxyuridine administration to label proliferating cells and immunohistochemistry to characterize the cell phenotype using neuron markers TUC 4, PSA-NCAM, Calbindin D28K and glial marker GFAP. At 16 days of age in MAM-treated rats we observed a significant decrease of BrdU-positive cells. Consistently, a decrease in density and number of granule cells was found compared to the controls. At 90 days the dentate gyrus of treated rats showed a complete recovery: no differences in the density, total number of neurons, the BrdU- and TUC 4-positive cells were revealed with respect to the controls. No deficits were evident in performance on the water maze in MAM-treated rats. These data suggest that the dentate gyrus is able to re-establish the proliferative zone and to rebuild the granule cell layer following neonatal MAM administration.
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PMID:Postnatal development of rat dentate gyrus: effects of methylazoxymethanol administration. 1179 35

Administration of NMDA receptor antagonists upregulates the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) in the adult hippocampus. Since the piriform cortex is also populated by PSA-NCAM immunoreactive neurons during adulthood, we sought to characterize them in detail and to test whether NMDA receptor antagonists also modulate PSA-NCAM in this cortical region. PSA-NCAM immunoreactivity is located mainly in layer II, where many neurogliaform and some pyramidal-semilunar transitional neurons are labeled. Many large neurons in layer III and endopiriform nucleus also express PSA-NCAM. Interestingly, some small labeled cells resembling migratory neuroblasts appear in these layers and in the ventral end of the corpus callosum subjacent to the piriform cortex. These putative migratory cells and some neurogliaform neurons in layer II do not express NeuN, a marker of differentiated neurons. Many of these PSA-NCAM immunoreactive cells also express doublecortin, a molecule involved in neuronal migration. The number of PSA-NCAM immunoreactive neurogliaform neurons increases significantly 7 days after the administration of an NMDA receptor antagonist. Moreover, 21 days after the treatment we observe a significant increase in the number of doublecortin expressing cells in the deep layers of the piriform cortex. These results expand the current knowledge of the neuronal populations expressing PSA-NCAM in the piriform cortex, suggesting that some of these cells could be involved in structural plastic events such as axonal outgrowth, synaptogenesis or even neuronal migration. Similar to the hippocampus, NMDA receptors appear to play a critical role in these processes in the adult piriform cortex.
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PMID:PSA-NCAM expression in the piriform cortex of the adult rat. Modulation by NMDA receptor antagonist administration. 1182 Oct 5

Since its first description the polysialylated form of NCAM (PSA-NCAM) is thought to be a major regulator of cell-cell interactions in the nervous system. Over the past few years many crucial questions have been answered concerning PSA biosynthesis and function. Among these are the identification and cloning of the key enzymes that are responsible for its synthesis and the fact that expression of PSA is not restricted to developmental stages but maintained in the adult nervous system. In the adult, PSA has been shown to be not only a marker of structural plasticity but seems to be a major player in these processes. Originally suggested to be a purely anti-adhesive factor, modulating cell-cell interactions in general and by this allowing plasticity, there is now increasing evidence that this might not be the whole story. Instead, it appears possible that PSA-NCAM interacts with secreted signaling molecules and by this fulfills a more instructive function in brain plasticity.
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PMID:Revisiting the function of PSA-NCAM in the nervous system. 1183 54


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