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

The gyrus dentatus is one of the few areas of the brain that continues to produce neurons after birth. The newborn cells differentiate into granule cells which project axons to their postsynaptic targets. This step is accompanied by the transient expression of the polysialylated isoforms of neuronal cell adhesion molecules (PSA-NCAM) by the developing neurons. Glucocorticoid hormones have been shown to inhibit neurogenesis. We noted a functional correlation between PSA-NCAM expression and glucocorticoid action after manipulation of corticosterone levels in the adrenalectomized rat. Adrenalectomy increased neurogenesis, evaluated from the incorporation of 5-bromo-2'-deoxyuridine in neuronal precursors, as well as PSA-NCAM expression. The increase in PSA-NCAM-immunoreactive (IR) cells in the gyrus dentatus, evidenced 72 h following adrenalectomy, persisted for at least a month. It was accompanied by enhanced dendritic arborization of PSA-NCAM-IR cells in the gyrus dentatus and by an increase in number of PSA-NCAM-IR fibres in the CA3 subfield. Neurogenesis was normalized by restitution of diurnal or nocturnal levels of corticosterone, whereas normalization of PSA-NCAM expression was only observed after simulation of the complete circadian fluctuation of the hormone. Our findings reveal the complex action of corticosterone in modulating the expression of PSA-NCAM in the gyrus dentatus of the hippocampal formation. They also highlight the importance of corticosterone fluctuations in the control of neurogenesis and plasticity in this structure.
 ...
PMID:Complex regulation of the expression of the polysialylated form of the neuronal cell adhesion molecule by glucocorticoids in the rat hippocampus. 975 69

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.
 ...
PMID:[Polysialylated NCAM in CSF, a marker for invasive medulloblastoma]. 975 72

The distribution and modulation of neural cell adhesion molecule polysialylation state (NCAM PSA) and the consequence of antisense inactivation of the Kv1.1 potassium channel was investigated following avoidance learning in mice. PSA immunoreactivity was most notable on cells at the inner denate border and in cortical layer II. Task acquisition resulted in a significant 30% transient increase in the frequency of dentate polysialylated neurons at the 12 h post-training time. In contrast, animals pretreated with the Kv1.1 antisense oligonucleotide exhibited both attenuated recall avoidance latencies and polysialylated cell frequency. As Kv1.1 is enriched on the dendrites of these granule-like cells, the attenuated polysialylation response is considered secondary to NCAM-mediated events during their transient synapse production in the 6-8 h post-training period.
 ...
PMID:Kv1.1 channel antisense attenuates learning and modulation of dentate polysialylated NCAM. 976 Jan 10

Most LHRH neurons actively migrate from the olfactory epithelium to the forebrain during embryonic days (ED) 3.5-8. When a small piece of the membrane filter was placed on the central course of the olfactory nerve in ED 3.5-5 chick embryos, LHRH neurons deviated from their regular migratory course at ED 6.5-7.5 to follow a route along the PSA-NCAM-positive medial and lateral nasal branches of the ophthalmic nerve of the trigeminal nerve. The olfactory nerve fibers which were specifically immunoreactive for somatostatin also deviated into the ophthalmic nerve. Enzymatic removal of PSA using endoneuraminidase did not interfere with the migration of LHRH neurons into the ophthalmic nerve bundle of the trigeminal nerve. The presence of structural supports seems to be primarily of importance in the migration of LHRH neurons along the olfactory and trigeminal nerve bundles. PSA may be less important for the migration of the LHRH neurons along peripheral neural elements.
 ...
PMID:LHRH neurons migrate into the trigeminal nerve when the developing olfactory nerve fibers are physically interrupted in chick embryos. 984 37

Neuronal loss and axonal sprouting are the most typical histopathological findings in the hippocampus of patients with drug-refractory temporal lobe epilepsy (TLE). It is under dispute, however, whether remodeling of neuronal circuits is a continuous process or whether it occurs only during epileptogenesis. Also, little is known about the plasticity outside of the hippocampus. We investigated the immunoreactivity of the highly polysialylated neural cell adhesion molecule (PSA-NCAM) in the surgically removed hippocampus and the entorhinal cortex of patients with drug-refractory TLE (n=25) and autopsy controls (n=7). Previous studies have shown that the expression of PSA-NCAM is associated with the induction of synaptic plasticity, neurite outgrowth, neuronal migration, and events requiring remodeling or repair of tissue. In patients with TLE, the optical density (OD) of punctate PSA-NCAM immunoreactivity was increased both in the inner and outer molecular layers of the dentate gyrus, compared with controls. The intensity of PSA-NCAM immunoreactivity in the inner molecular layer correlated with the duration of epilepsy, severity of hippocampal neuronal loss, density of mossy fiber sprouting, and astrogliosis. In TLE patients with only mild neuronal loss in the hippocampus, the density of infragranular immunopositive neurons was increased twofold compared with controls, whereas in TLE patients with severe neuronal loss, the infragranular PSA-NCAM-positive cells were not present. In the hilus, the somata and tortuous dendrites of some surviving neurons were intensely stained in TLE. PSA-NCAM immunoreactivity was also increased in CA1 and in layer II of the rostral entorhinal cortex, where immunopositive neurons were surrounded by PSA-NCAM-positive fibers and puncta. Our data provide evidence that synaptic reorganization is an active process in human drug-refractory TLE. Moreover, remodeling is not limited to the dentate gyrus, but also occurs in the CA1 subfield and the entorhinal cortex.
 ...
PMID:Remodeling of neuronal circuitries in human temporal lobe epilepsy: increased expression of highly polysialylated neural cell adhesion molecule in the hippocampus and the entorhinal cortex. 985 37

Serum concentrations of polysialylated neural cell adhesion molecule (PSA-NCAM), a developmentally regulated form of the NCAM, have been recently described to be elevated in children with rhabdomyosarcoma and neuroblastoma, proving PSA-NCAM to be a tumor marker of diagnostic relevance to these malignancies. The present investigation was undertaken to define age-dependent reference intervals in normal children. Serum concentrations of polysialylated NCAM were determined in 366 children aged newborn to 17 y and in 18 adult patients by an immunoluminescence assay using the polysialic acid-specific MAb 735. Serum levels in newborn children were 51.7 kU/L (mean +/- 12.0 kU/L SD), whereas in adult patients they were 9.9 kU/L (mean +/- 3.5 kU/l SD). Assigning the patients to 14 different age groups, a gradual decay of PSA-NCAM serum concentrations was observed, and therefore, mean levels and empirical interpolated percentiles were determined for every age group. Applying specially fitted logistic functions, two different sigmoid graphs were obtained describing the age-dependent decrease of serum PSA-NCAM during the neonatal period and during childhood. The age at which the levels reach half the initial value was located at 3.1 d (mean +/- 2 d SE) and 14 y (mean +/- 1 y SE), respectively. There was no difference between male and female individuals. Repeated measurements revealed variations below 10%. For the first time, our study describes serum levels of PSA-NCAM in children of different age and their gradual decay until adulthood.
 ...
PMID:Polysialylated neural cell adhesion molecule serum levels in normal children. 985 27

Luteinizing hormone-releasing hormone (LHRH) neurons migrate from the olfactory placode to the forebrain in association with vomeronasal nerves (VNN) that express the polysialic acid-rich form of the neural cell adhesion molecule (PSA-NCAM). Two approaches were used to investigate the role of PSA-NCAM: injection of mouse embryos with endoneuraminidase N, followed by the analysis of LHRH cell positions, and examination of LHRH cell positions in mutant mice deficient in the expression of NCAM or the NCAM-180 isoform, which carries nearly all PSA in the brain. The enzymatic removal of PSA at embryonic day 12 significantly inhibited the migration of nearly half of the LHRH neuron population, without affecting the VNN tract itself. Surprisingly, the absence of NCAM or NCAM-180 did not produce this effect. However, a shift in the route of migration, resulting in an excess number of LHRH cells in the accessory olfactory bulb, was observed in the NCAM-180 mutant. Furthermore, it was found that PSA expressed by the proximal VNN and its distal branch leading to the accessory bulb, but not the branch leading to the forebrain, was associated with the NCAM-140 isoform and thus was retained in the NCAM-180 mutant. These results provide two types of evidence that PSA-NCAM plays a role in LHRH cell migration: promotion of cell movement along the VNN tract that is sensitive to acute (enzymatic), but not chronic (genetic), removal of PSA-NCAM, and a preference of a subset of migrating LHRH cells for a PSA-positive axon branch over a PSA-negative branch in the NCAM-180 mutant.
 ...
PMID:Polysialic acid facilitates migration of luteinizing hormone-releasing hormone neurons on vomeronasal axons. 988 May 99

Multipotent neural progenitor species present within developing and adult periventricular generative zones can give rise to all of the major cellular elements of the brain. Although lineage specification during development has been thought to be restricted to these generative zones, we have utilized quantitative immunoselection techniques to isolate an enriched population of multipotent neural progenitor cells that express polysialylated neural cell adhesion molecule (PSA-NCAM) from postnatal day 2 cerebral cortex independent of generative zones. This population of cerebral cortical progenitor cells exhibited robust proliferation in response to epidermal growth factor and subsequently gave rise to clonally derived neurons, astrocytes, and oligodendrocytes. Quantitative regional analysis further demonstrated that while the multipotent cells derived from the cerebral cortex uniformly expressed PSA-NCAM, multipotent cells derived from generative zones contained equal proportions of PSA-NCAM-positive and -negative multipotent progenitor cells. The generation of individual cellular lineages from cortical multipotent progenitors could be enhanced by specific cytokines that are expressed within the cerebral cortex. Further, while oligodendroglial progenitor cells derived from cortical multipotent progenitors exhibited responsiveness to platelet-derived growth factor (PDGF) and neurotrophin-3 (NT-3), primary cultures of cortical oligodendroglial progenitors were responsive to PDGF but not to NT-3. These observations suggest that in addition to glial progenitors that commit to a specific lineage prior to migration from generative zones, there is within the cerebral cortex a separate pool of multipotent cells that are capable of generating mature glial progeny in response to specific environmental cues. Therapeutic interventions aimed at differentiation of endogenous cerebral pools of multipotent progenitors may provide a novel strategy for amelioration of the sequelae of environmental and genetic insults to the postnatal cerebrum.
 ...
PMID:Isolation and developmental characterization of cerebral cortical multipotent progenitors. 988 91

Levels of immunoreactivity for highly polysialylated neural cell adhesion molecule (PSA-NCAM), NCAM, and tenascin-C (TN-C), were examined in the basal ganglia regions and hypothalamic nuclei of adult rats after serotonergic (5-HT) lesions induced by 5,7-dihydroxytryptamine injections in the dorsal and medial raphe nuclei. Decreases in the density of serotonin fibers were associated with no changes in NCAM and general decreases in PSA-NCAM staining, the time-course of changes being selective for each region. Taken that the confocal analysis indicated that serotonin neurons do not express PSA-NCAM and that similar decreases in PSA-NCAM staining were observed after inhibition of 5-HT synthesis induced by parachlorophenylalanine administration, these results suggest that 5-HT may reduce adhesion by acting on PSA-NCAM expression in its environment, and thus facilitate plasticity in adult brain. Two months after the neurotoxin lesions, a normalization of PSA-NCAM staining was associated with a partial restoration in 5-HT fiber density in the nucleus accumbens and the supraoptic nucleus, suggesting that PSA-NCAM may facilitate sprouting of 5-HT fibers. Since a similar normalization was also detected in the suprachiasmatic nucleus, which remained deprived of serotonin fibers, negative factors are likely to be involved in regeneration processes. Indeed, increases in glial fibrillary acidic protein (GFAP) followed by increases in TN-C were observed in these areas, suggesting that the secretion of TN-C by astrocytes may have negative consequences on the sprouting of 5-HT fibers. Finally, the lack of changes in striatal PSA-NCAM or TN-C staining observed after selective lesions of the dopaminergic pathway induced by intranigral injections of 6-hydroxydopamine indicates that 5-HT has a selective and critical role in adult brain plasticity.
 ...
PMID:Serotonin depletion in the adult rat produces differential changes in highly polysialylated form of neural cell adhesion molecule and tenascin-C immunoreactivity. 989 Apr 34

Modulation of neural cell adhesion molecule polysialylation (NCAM PSA) state has been proposed to underlie morphofunctional change associated with consolidation of memory in the rodent, and its age-dependent decline to be related to impaired cognitive function. To establish whether this may be a human correlate of cognitive decline, we determined the age-dependent expression of PSA in the human hippocampal dentate gyrus using postmortem tissue derived from individuals who exhibited no obvious neuropathology. As in the rodent, PSA immunoreactivity in the 5-month human infant was associated mainly with a population of granule-like cells and their mossy fibre axons. Cell numbers were maximal during the first 3 years of life but declined by an order of magnitude between the second and third decades and remained relatively constant thereafter and was restricted to the granule cell layer/hilar border. In contrast to the rodent, diffuse immunostaining was observed in the inner molecular layer; however, as development advanced, this became relocated to the outer molecular layer from 2 years of age onwards. In addition, numerous polysialylated hilar neurons became evident at 2-3 years of age and remained constant until the eighth decade of life. These findings suggest NCAM polysialylation to play a crucial developmental role within a period concluding with adolescence, and that an attenuated NCAM PSA-mediated neuroplasticity continues throughout the human lifespan. The importance of the developmental phase of NCAM PSA expression in the emergence of schizophrenia is discussed.
 ...
PMID:Polysialylated neural cell adhesion molecule expression in the dentate gyrus of the human hippocampal formation from infancy to old age. 989 Apr 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>