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)

Puberty in primates is triggered by a gonad-independent reinitiation of a pulsatile mode of GnRH release. The purpose of the present study was to begin to examine the hypothesis that this neuroendocrine event is the result of structural or plastic changes within the neural network governing the activity of GnRH neurons. Specifically, we sought to determine whether polysialic acid neural cell adhesion molecule (PSA-NCAM), a plasma membrane-associated glycoprotein that has previously been proposed to be a marker for postnatal neuronal plasticity, was expressed within GnRH neuron containing areas of the rhesus monkey hypothalamus. The study employed male monkeys that were castrated prepubertally. Immunocytochemistry of hypothalamic tissue from four animals of pubertal age employing a monoclonal antibody (12F8) specific for PSA-NCAM revealed the presence of PSA-NCAM immunoreactivity within the region of the arcuate nucleus and median eminence of the medial basal hypothalamus (MBH) and in the region of the organum vasculosum of the lamina terminalis of the rostral hypothalamus, two areas in the monkey brain where GnRH neurons are concentrated. As expected, immunostaining for total NCAM using a polyclonal rabbit antibody to mouse total NCAM was uniformly distributed throughout hypothalamic sections containing the MBH. Double staining showed that some, though not all, GnRH cell bodies of the MBH were located within the PSA-NCAM-immunopositive region of the arcuate nucleus and the median eminence. The pattern of PSA-NCAM immunoreactivity in the MBH of three prepubertal monkeys was similar to that seen for the older animals. Western analysis of a membrane extract from the MBH of a monkey of pubertal age, employing antibody 12F8, identified a broad band of staining at the expected molecular weight for this adhesion molecule. A similar, but less intense, immunoreactive band was observed for the preoptic area. In contrast, an immunoblot of a membrane extract of cerebral cortex was only faintly positive for PSA-NCAM. Taken together, the foregoing findings are consistent with the notion that structural changes within the MBH may underlie the pubertal reinitiation of pulsatile GnRH release. Moreover, the presence of PSA-NCAM in the MBH of prepubertal monkeys suggests that the role, if any, of this molecule in the onset of sexual maturation in primates is permissive in nature.
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PMID:Postnatal expression of polysialic acid-neural cell adhesion molecule in the hypothalamus of the male rhesus monkey (Macaca mulatta). 769 45

Muscle development in vivo involves a complex sequence of cell-cell interactions in which secondary myotubes first form in association with primary myotubes and subsequently separate from them. We show here that during this process N-cadherin and the different structural forms of NCAM are regulated in a pattern that involves both temporal changes in expression and localization to particular regions of the muscle cell surface. In particular, levels of N-cadherin on maturing myotubes are decreased, and the form of NCAM synthesized by the muscle changes from a transmembrane non-polysialylated to a lipid-linked polysialylated membrane protein. Moreover, while NCAM was distributed on all myotube surfaces, the polysialyated form of NCAM was restricted to regions of the myotube surface that had recently separated from neighboring cells. We previously found that blockade of nerve-induced activity by d-Tubocurarine perturbed muscle cell interactions, resulting in a failure of myotubes to separate. We now show that this activity blockade also alters adhesion molecule expression. First, N-cadherin was no longer down-regulated in maturing myotubes, and its persistence on the surfaces of mature myotubes may partly explain their failure to separate. Secondly, the developmental switch from transmembrane to lipid-linked NCAM did not occur, and polysialylated NCAM was no longer formed. As the unusual physical properties of PSA have been proposed to impede cell-cell interactions, this alteration would also be expected to compromise cell separation. Together, these results suggest that the regulated expression of both N-cadherin and NCAM isoforms including their polysialylation, is an essential mechanism for the normal separation of secondary myotubes from primary myotubes.
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PMID:Regulation and activity-dependence of N-cadherin, NCAM isoforms, and polysialic acid on chick myotubes during development. 827 4

The myelination of the axons of the central nervous system (CNS) is assumed by the oligodendrocytes, which depend at least in part on signals of axonal origin. The axonal influence on myelination seems to consist of the sum of positive and negative factors, which can either act on the axon or on the oligodendrocyte, allowing the neuron to decide when and where myelinization is initiated. The induction factors appear to be mediated, in some cases, by electrical activity. Among the negative factors, certain factors such as the adhesion molecule PSA-NCAM seem to act by inhibiting the adhesion between the axon and the oligodendrocytic extension. Others, such as the inhibitory signalling pathway, jagged1/Notch1, appear to trigger an inhibitory oligodendroglial signalling, therapy preventing maturation and myelination. The recent determination of the role of these axonal signals has provided a new approach to the mechanisms of normal myelination. These results could be extrapolated to the process of remyelination in human demyelinating pathologies such as multiple sclerosis, and open up new therapeutic research possibilities aimed at neuronal protection.
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PMID:[Role of axonal signals in myelination of the central nervous system]. 1072 13

The potential of mature central nervous system (CNS) neurons to regenerate after injury represents a fundamental issue in neurobiology. The regional expression of proteins associated with axonal elongation, such as microtubule-associated protein 1B (MAP1B), its phosphorylated isoform (MAP1B-P), growth-associated protein 43 (GAP-43), and polysialylated neural cell-adhesion molecule (PSA-NCAM), was examined using immunohistochemistry from 24 hours to 2 months following lateral fluid percussion brain injury of moderate severity (2.4-2.6 atmospheres) in anesthetized rats. Uninjured (control) rats were subjected to anesthesia and surgery without injury or were subjected to anesthesia alone. Within the site of maximal injury, only increases in MAP1B and MAP1B-P were observed. Increased immunoreactivity was observed bilaterally for all growth-related proteins that were evaluated. By 24 hours postinjury, MAP1B and MAP1B-P increased within the cortex (P < 0.01) and the hippocampus (P < 0.001), whereas MAP1B-P also was elevated in the thalamus (P < 0.05). Within the dentate gyrus, increased immunoreactivity was observed for all proteins examined. By 48 hours postinjury, GAP-43 was elevated bilaterally within the inner molecular layers of the dentate gyrus (P < 0.005) and within the stratum lacunosum moleculare (P < 0.01), the stratum radiatum (P < 0. 005), and the stratum oriens (P < 0.05) of the hippocampus. Increased numbers of PSA-NCAM-labeled neurons were observed in the granule cell layers of the dentate gyrus from 48 hours through 2 weeks postinjury (P < 0.0005). The bilateral nature of increased expression of growth-related proteins differs from unilateral patterns of neuronal degeneration previously characterized for the lateral fluid-percussion model of brain injury. Taken together, these results suggest the existence of a temporary posttraumatic state in which the CNS may have increased regenerative potential. Enhancement of such a response may be one therapeutic strategy in treating CNS injury.
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PMID:Bilateral growth-related protein expression suggests a transient increase in regenerative potential following brain trauma. 1090 17

Cell adhesion molecule expression has been linked to disease outcome in prostatic adenocarcinomas (PACs). We evaluated the coordinated expression of catenin-related proteins, E-cadherin, N-cadherin, and CD44s in PACs. Archival sections from 112 PACs were immunostained by an automated method (Ventana Medical Systems, Tucson, AZ) using monoclonal antibodies to alpha- and beta-catenins, p120CTN, E-cadherin, N-cadherin, and CD44s proteins. Immunoreactivity was semiquantitatively scored, and results were evaluated for association between these markers. Staining results were also correlated with tumor grade, stage, ploidy, preoperative serum PSA, and postoperative biochemical disease recurrence. Decreased expression of alpha- and beta- catenins, p120CTN, E-cadherin, and CD44s proteins (range, 5% to 49%) was noted in PACs, and downregulation of each of these proteins correlated with high tumor grade (P =.02 to.0001). Although loss of E-cadherin and p120CTN each correlated with stage (E-cadherin, P =.02; p120CTN, P =.02) and ploidy (E-cadherin, P =.0001; p120CTN, P =.004), downregulation of CD44s correlated with ploidy (P =.002), serum PSA (P =.005), and postoperative disease recurrence (P =.02). N-cadherin was positive in only 5% of PACs and did not correlate with any prognostic parameters. alpha-Catenin downregulation correlated with decreased expression of E-cadherin (P =.0001). Additionally, decreased expression of each of these 2 proteins respectively correlated with loss of beta-catenin (P =.0001 and.004), p120CTN (P =.005 and.001), and CD44s (P =.008 and.01). beta-Catenin expression levels correlated with p120CTN (P =.01). A trend for co-downregulation of CD44s and p120CTN and of CD44s and beta-catenin was observed. In conclusion, the significant association between decreased expression of various members of the CAM family of proteins supports their collective role in mediating cell-cell adhesion. Altered expression of these proteins may be of prognostic value in patients with prostate cancer.
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PMID:Co-downregulation of cell adhesion proteins alpha- and beta-catenins, p120CTN, E-cadherin, and CD44 in prostatic adenocarcinomas. 1152 Dec 30

Cell adhesion molecule function is involved in hippocampal synaptic plasticity and is associated with memory consolidation. At the infragranular zone of the dentate gyrus, neurons expressing the polysialylated form of the neural cell adhesion molecule (NCAM PSA) transiently increase their frequency at the 12-hr posttraining time in behaviours elicited by stressful stimuli, such as those associated with conditioned avoidance, water maze, and fear conditioning paradigms. To determine whether learning-induced modulation of NCAM polysialylation is limited to stressful paradigms, we employed a reward-based odour discrimination task. Animals show a rapid acquisition and recall of this task in terms of latency to identify the food-associated odour and the number of choice errors. Immunohistochemical procedures were employed to determine the change in NCAM PSA expression following task acquisition. NCAM PSA immunoreactivity in the hippocampal formation was most intense on the granule-like neurons in the infragranular zone of the dentate gyrus, and their frequency transiently increased in the 12-hr posttraining period. The nature of the transient increase in NCAM PSA-immunoreactive neurons was indistinguishable from that observed following avoidance conditioning or spatial learning, in that it occurred at the same time. The transient increase in NCAM PSA expression is suggested to facilitate dendritic elaboration in response to the acquisition of novel behavioural repertoires.
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PMID:Consolidation of memory for odour-reward association requires transient polysialylation of the neural cell adhesion molecule in the rat hippocampal dentate gyrus. 1459 1

Retinoic acid is well recognized to promote neuronal differentiation in the embryonic nervous system, but how it influences the postnatal cerebral cortex remains largely unknown. The domain of highest retinoic acid actions in the cortex of the mouse constricts postnatally to a narrow band that includes the dorsal visual stream and the attentional and executive networks. This band of cortex, which is distinguished by the retinoic acid-synthesizing enzyme RALDH3, exhibits signs of delayed maturation and enhanced plasticity compared to the surrounding cortex, as indicated by suppression of parvalbumin, neurofilament, cytochrome oxidase and perineuronal net maturation, and persistence of the embryonic, polysialated form of the neural cell-adhesion molecule PSA-NCAM. During the first postnatal week, the RALDH3-expressing territory translocates in the caudal cortex from the medial limbic lobe to the adjacent neocortex. This topographical shift requires the neurotrophin NT-3 because in mice lacking neuronal NT-3 the RALDH3 enzyme maintains its early postnatal pattern up to adulthood. In the NT-3-null mutants, expression of the markers, whose topography colocalizes with RALDH3 in the normal cortex, matches the abnormal RALDH3 pattern. This indicates that the uneven retinoic acid distribution serves a role in patterning the maturation and to some extent function of the normal postnatal cerebral cortex.
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PMID:Retinoic acid delineates the topography of neuronal plasticity in postnatal cerebral cortex. 1683 33

The proliferative activity of neural precursors from the subventricular zone (SVZ) was investigated after a unilateral lesion was formed in the nigrostriatal pathway in adult rats. The lesion was formed by unilateral injection of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway, and then bromodeoxyuridine (BrdU) was injected (ip) for 4 days or 2 weeks 10 days after the lesion was formed. The rats were killed, and the brain sections were immunohistochemically stained to detect the expression of BrdU, polysialylated neural-cell-adhesion molecule (PSA-NCAM), glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH) in the SVZ and the striatum (STR). The results showed that the BrdU(+) cells increased significantly in the SVZ, ipsilateral to the lesion at 2 weeks after the lesion. The PSA-NCAM(+) and GFAP(+) cells were also increased in the SVZ at this time. Some BrdU-labeled cells were seen in the same side of the STR and were double-labeled with PSA-NCAM. These cells had a tendency to migrate from the SVZ to the STR. The number of positive cells decreased at 4 weeks after the lesion was formed. The number of nigrostriatal projections with TH(+) decreased significantly in the STR on the lesion side, and the level of decrease was related to the quantity of BrdU-labeled cells at 2 weeks. These results indicate that the neural precursors in the SVZ of adult rats may increase after a lesion has been formed in the nigrostriatal pathway, and these cells might migrate into the STR on the same side.
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PMID:Proliferation of neural precursors in the subventricular zone after chemical lesions of the nigrostriatal pathway in rat brain. 1684 44

The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is involved in several morphogenetic processes of the central nervous system. In the present study the expression of PSA-NCAM has been investigated in the rat thalamus during embryonic and postnatal development using light and electron microscopic immunocytochemical techniques. At all the examined ages, PSA-NCAM staining in the thalamus was mainly observed along neuronal plasmatic membranes and absent in astrocytes identified by labelling with cytoskeletal (vimentin and glial fibrillary acidic protein) and membrane (GABA transporter-3) markers. At embryonic day 14 the immunoreactivity was restricted to the dorsal thalamic mantle and to the region of reticular thalamic migration and subsequently it extended throughout the whole thalamic primordium. PSA-NCAM labelling remained intense and homogeneously distributed along perinatal period, but from P4 it began to decrease selectively, persisting throughout adulthood only in the reticular nucleus, ventral lateral geniculate nucleus and midline and intralaminar nuclei. The expression of this adhesion molecule differed in areas characterized by the presence of neurons containing distinct calcium binding proteins, as PSA-NCAM labelling was intense around calretinin-positive neurons, whereas it decreased in some calbindin-immunoreactive regions. These findings show evidence of a selective neuronal expression of PSA-NCAM in developing thalamus, supporting its suggested role in cell migration and synaptogenesis as it occurs in the cerebral cortex. In adulthood PSA-NCAM could instead be a marker of thalamic nuclei that retain a potential for synaptic plasticity.
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PMID:PSA-NCAM in the developing and mature thalamus. 1729