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

The polysialylated neural cell adhesion molecule (PSA-NCAM) plays a role in axonal development and synaptic plasticity. Its pattern of expression is regulated temporally and topographically in the brain during development. However, it is unclear whether or not its subcellular location also changes. We have examined PSA-NCAM expression in relation to synapse formation in the developing rat striatum with immunohistochemistry and electron microscopy. Early in development, PSA-NCAM was present along the cytoplasmic membranes of neurons and in growth cones. PSA-NCAM expression became progressively confined to pre- and postsynaptic elements as neurons matured morphologically. Confirming previous results, a marked increase in the density of asymmetric synapses determined by using the physical dissector method was observed in the dorsolateral striatum between postnatal day 14 (P14) and P18. It was followed by a reduction between P18 and P25, when asymmetric synapse density reached adult levels. In contrast, the density of symmetric synapses had surpassed adult levels by P14. In the dorsomedial striatum, the density of asymmetric and symmetric synapses was similar at P18, at P25, and in adults. PSA-NCAM was associated with most asymmetric and symmetric synapses at P14 and P18 and was expressed in both pre- and postsynaptic elements of a majority (P14) or approximately half (P18) of the synapses. Most synapses lost PSA-NCAM expression between P18 and P25 in the dorsolateral striatum and between P25 and adult in the dorsomedial striatum. The data indicate that PSA-NCAM expression becomes restricted topographically during neuronal maturation but remains strategically associated with developing synapses during late postnatal development in the striatum.
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PMID:Synaptogenesis and ultrastructural localization of the polysialylated neural cell adhesion molecule in the developing striatum. 1002 11

Neuronal microtubules have unique stability properties achieved through developmental regulation at the expression and post-translational levels on tubulins and microtubule associated proteins. One of the most specialized tubulins specific for neurons is class-III beta-tubulin (also known as beta6-tubulin). Both the upregulation and the post-translational processing of class-III beta-tubulin are believed to be essential throughout neuronal differentiation. The present investigation documents the temporal and spatial patterns of class-III beta-tubulin expression throughout neurogenesis. For this study a novel polyclonal antiserum named U-beta6, specific to unphosphorylated class-III beta-tubulin has been developed, characterized and compared with its commercial homologue TuJ-1. Our experiments indicate that the two antibodies recognize different forms of class-III beta-tubulin both in vitro and in vivo. Biochemical data revealed that U-beta6 bound unphosphorylated soluble class-III beta-tubulin specifically, while TuJ-1 recognized both the phosphorylated and unphosphorylated forms of the denatured protein. In vivo U-beta6 was associated with neurogenesis and labelled newly committed CNS and PNS neuroblasts expressing neuroepithelial cytoskeletal (nestin and vimentin) and surface markers (the anti-ganglioside supernatant, A2B5 and the polysialic acid neural adhesion molecule, PSA-NCAM), as well as differentiating neurons. These studies with U-beta6 illustrate three main developmental steps in the neuronal lineage: the commitment of neuroepithelial cells to the lineage (U-beta6 +ve/TuJ-1 -ve cells); a differentiation stage (U-beta6 +ve/TuJ-1 +ve cells); and, finally, neuronal maturation correlating with a drop in unphosphorylated class-III beta-tubulin immunostaining levels. These investigations also conclude that U-beta6 is an earlier marker than TuJ-1 for the neuronal lineage in vivo, and it is thus the earliest neuronal lineage marker known so far.
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PMID:Expression of unphosphorylated class III beta-tubulin isotype in neuroepithelial cells demonstrates neuroblast commitment and differentiation. 1005 52

Neuronal microtubules have unique stability properties achieved through developmental regulation at the expression and posttranslational levels on tubulins and microtubule associated proteins. One of the most specialized tubulins specific for neurons is class-III beta-tubulin (also known as beta6-tubulin). Both the upregulation and the post-translational processing of class-III beta-tubulin are believed to be essential throughout neuronal differentiation. The present investigation documents the temporal and spatial patterns of class-III beta-tubulin expression throughout neurogenesis. For this study a novel polyclonal antiserum named U-beta6, specific to unphosphorylated class-III beta-tubulin has been developed, characterized and compared with its commercial homologue TuJ-1. Our experiments indicate that the two antibodies recognize different forms of class-III beta-tubulin both in vitro and in vivo. Biochemical data revealed that U-beta6 bound unphosphorylated soluble class-III beta-tubulin specifically, while TuJ-1 recognized both the phosphorylated and unphosphorylated forms of the denatured protein. In vivo U-beta6 was associated with neurogenesis and labelled newly committed CNS and PNS neuroblasts expressing neuroepithelial cytoskeletal (nestin and vimentin) and surface markers (the anti-ganglioside supernatant, A2B5 and the polysialic acid neural adhesion molecule, PSA-NCAM), as well as differentiating neurons. These studies with U-beta6 illustrate three main developmental steps in the neuronal lineage: the commitment of neuroepithelial cells to the lineage (U-beta6 +ve/TuJ-1-ve cells); a differentiation stage (U-beta6 +ve/TuJ-1 +ve cells); and, finally, neuronal maturation correlating with a drop in unphosphorylated class-III beta-tubulin immunostaining levels. These investigations also conclude that U-beta6 is an earlier marker than TuJ-1 for the neuronal lineage in vivo, and it is thus the earliest neuronal lineage marker known so far.
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PMID:Expression of unphosphorylated class III beta-tubulin isotype in neuroepithelial cells demonstrates neuroblast commitment and differentiation. 1007 18

In the brain of adult rodents, young neurons arising from the subventricular zone (SVZ) of the lateral ventricle migrate tangentially along the rostral migratory stream (RMS) toward the olfactory bulb. The aim of this study was to determine whether surgical lesions placed through the RMS could affect the rostral migration of these newly formed neurons. Confocal and electron microscopy were used to characterize their anatomical organization within the intact and lesioned forebrains. As soon as 7 days and up to 45 days after placing a surgical lesion through the proximal portions of the RMS, numerous cells immunostained for polysialylated neural cell adhesion molecule (PSA-NCAM) were detected both (1) throughout the lesional cavity extending from the cortex to the anterior commissura, and (2) within the tissue located caudal to the lesion. In both regions, these PSA-NCAM-immunostained cells were labeled for neuronal markers but were negative for glial fibrillary acidic protein (GFAP). After administration of the proliferation marker bromodeoxyuridine (BrdU), nuclear labeling was associated with cells immunostained for PSA-NCAM but GFAP-negative, that accumulated within the lesional cavity and in the tissue caudal to the lesion. For the longest postlesional delays, a number of the PSA-NCAM-immunostained neurons located in various portions of the lesional cavity exhibited intense immunostaining for gamma-aminobutyric acid, whereas only a few of them exhibited faint immunostaining for tyrosine hydroxylase. These data indicate that surgical lesions placed through the RMS of adult rats impede the migration toward the olfactory bulb of the neuroblasts arising from the SVZ, inducing their accumulation and their partial differentiation in forebrain regions caudal to the lesion.
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PMID:Tangential migration of young neurons arising from the subventricular zone of adult rats is impaired by surgical lesions passing through their natural migratory pathway. 1009 42

Ageing is accompanied by a decline in neurogenesis and in polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) expression within the hippocampus and by elevated basal levels of circulating corticosterone. In a companion study, we demonstrated that suppression of corticosterone by adrenalectomy increased neurogenesis and PSA-NCAM expression in the dentate gyrus of adult rats. Here we show that adrenalectomy increased neurogenesis in this structure in old rats, as measured by the incorporation of 5-bromo-2'-deoxyuridine in neuronal progenitors. This effect was prevented by corticosterone replacement. In contrast, PSA-NCAM expression remained unchanged in comparison with controls. Thus, in the aged brain, stem cells are still present and able to enter the cell cycle. This may point to ways of protecting or treating age-related cognitive impairments.
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PMID:Adrenalectomy increases neurogenesis but not PSA-NCAM expression in aged dentate gyrus. 1010 42

The highly polysialylated neural cell adhesion molecule (PSA-NCAM) is one of the most promising molecules that contributes to plasticity in the central nervous system. We evaluated PSA-NCAM immunoreactivity in the hippocampal formation of Alzheimer's disease (AD) patients. We found significant increases over control levels in the optical density ratios of PSA-NCAM immunoreactivity in the outer molecular layer/granule cell layer (ODoml/grl) and in the inner molecular layer/granule cell layer (ODiml/grl) in the dentate gyrus of AD patients. The optical density of the granule cell layer in the dentate gyrus did not differ significantly between AD patients and control subjects. However, the number of PSA-NCAM-immunopositive infragranule cells was higher in the AD group compared with control subjects. The major finding in the CA1, subiculum and entorhinal cortex of AD patients was the disorganization of PSA-NCAM-immunoreactive fibres. These results indicate that neuronal remodelling occurs, especially in the dentate gyrus of patients with AD.
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PMID:Hippocampal plasticity in Alzheimer's disease: changes in highly polysialylated NCAM immunoreactivity in the hippocampal formation. 1021 28

Purkinje cells can survive axotomy for as long as 18 months without retracting their severed axons. During this period of time, the fate of the terminal bulbs of axotomized Purkinje cell axons and their relationship with the glial scar were determined. Terminal axonal sprouting begins three months after the lesion and continuously increases up to 18 months (the longest survival time studied), when the sprouts establish synaptic contacts, mainly on granule cell dendrites at the glomeruli. Cellular changes in the glial scar were analyzed to determine whether the late onset and continuous increase of axonal sprouting could be correlated with an increase of permissive factors and/or a decrease of inhibitory factors for axonal growth. Activated macrophages disappeared much earlier than did the initiation of sprouting. Myelin and its associated neurite growth inhibitory molecules began to decrease from three months after the lesion. This decrease was uneven and not correlated spatially with the sprouting. Reactive astrogliosis was heterogeneous: only some of the reactive astrocytes expressed PSA-NCAM, the embryonic form of the neural cell adhesion molecule, a permissive substratum for neurite outgrowth. The expression of PSA-NCAM occurred concurrently with sprouting in the area of gliosis containing Purkinje cell sprouts. Moreover, the ultrastructural study showed that the majority of sprouts (75%) were totally ensheathed by astrocytic processes. Thus, long-term glial scars are permissive to axonal sprouting, suggesting that reactive astrocytes, either through the expression of permissive molecules or by preventing direct contact between axonal elements and myelin inhibitory molecules, regulate the sprouting.
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PMID:Late axonal sprouting of injured Purkinje cells and its temporal correlation with permissive changes in the glial scar. 1034 May 14

As transient and time-dependent modulations of neural cell adhesion molecule polysialylation (NCAM PSA) are associated with morphofunctional change and required for the consolidation of spatial and nonspatial forms of learning, we determined the demands imposed on this system by sequential training in the Morris water maze followed by the passive avoidance paradigm. Animals trained in this manner had recall of the water maze but not the passive avoidance response as judged by their escape and avoidance latencies, respectively. Activation of NCAM PSA on dentate neurons at the 12-h post-training time suggested information processing; however, this was significantly less than that predicted for coincident acquisition of both tasks. When sequential training was separated by an interparadigm period of 2 h, an enduring NCAM PSA activation was observed which was indistinguishable from the sum of the expected activations for each individual task. These observations suggest that the NCAM PSA response may become saturated when alternate tasks are presented without an intervening period.
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PMID:Sequential training in separate paradigms impairs second task consolidation and learning-associated modulations of hippocampal NCAM polysialylation. 1037 13

The granule cell layer of the adult dentate gyrus possesses two characteristics of an immature nervous system. The first is that granule cells continue to be generated in the innermost region of the granule cell layer, and newly generated and developing granule cells in the adult express highly polysialylated neural cell adhesion molecule (PSA-NCAM). PSA-NCAM-expressing apical dendrites have dynamically unstable processes such as irregular shafts and many stick-like or fan-shaped fine processes. The second is that radial glia-like cells expressing glial fibrillary acidic protein (GFAP) remain in a similar region of the granular layer. The numbers of PSA-NCAM-expressing granule cells and GFAP-expressing radial glia-like cells show a parallel age-dependent decrease during aging. Moreover, by using confocal laser scanning microscopy and immunoelectron microscopy, we demonstrated that PSA-NCAM-expressing dendrites and GFAP-expressing radial processes are partly in contact with each other, and occasionally the radial glial processes envelop the PSA-NCAM-positive dendritic processes. The temporal and spatial relationship between the two immature elements suggests that the processes of the radial glia-like cells are closely associated with the dendritic growth of the newly generated granule cells in the adult dentate gyrus and that these two immature features of neurons and glia in the dentate gyrus diminish with age.
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PMID:Temporal and spacial relationships between PSA-NCAM-expressing, newly generated granule cells, and radial glia-like cells in the adult dentate gyrus. 1040 15

To understand better how spontaneous motoneuron activity and intramuscular nerve branching influence motoneuron survival, we chronically treated chicken embryos in ovo with either d-tubocurarine (dTC) or muscimol during the naturally occurring cell death period, assessing their effects on activity by in ovo motility measurement and muscle nerve recordings from isolated spinal cord preparations. Because muscimol, a GABA(A) agonist, blocked both spontaneous motoneuron bursting and that elicited by descending input but did not rescue motoneurons, we conclude that spontaneous bursting activity is not required for the process of normal motoneuron cell death. dTC, which rescues motoneurons and blocks neuromuscular transmission, blocked neither spontaneous nor descending input-elicited bursting and early in the cell death period actually increased burst amplitude. These changes in motoneuron activation could alter the uptake of trophic molecules or gene transcription via altered patterns of [Ca(2+)](i), which in turn could affect motoneuron survival directly or indirectly by altering intramuscular nerve branching. A good correlation was found between nerve branching and motoneuron survival under various experimental conditions: (1) dTC, but not muscimol, greatly increased branching; (2) the removal of PSA from NCAM partially reversed the effects of dTC on both branching and survival, indicating that branching is a critical variable influencing motoneuron survival; (3) muscimol, applied with dTC, prevented the effect of dTC on survival and motoneuron bursting and, to a large extent, its effect on branching. However, the central effects of dTC also appear to be important, because muscimol, which prevented motoneuron activity in the presence of dTC, also prevented the dTC-induced rescue of motoneurons.
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PMID:Neuromuscular activity blockade induced by muscimol and d-tubocurarine differentially affects the survival of embryonic chick motoneurons. 1047 94


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