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)

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

An immunohistochemical study was performed in order to evaluate the sequence of expression of various cell surface proteins [neural cell adhesion molecule (NCAM) and its polysialylated isoform, PSA NCAM, and utrophin], cytoskeletal proteins (myosin heavy chain isoforms, desmin) and the transcription factor MyoD1 in regenerating mouse muscle fibers following treatment with sodium dihydrogen phosphate. The sequence of the regeneration process with this new myotoxic agent is similar to that which can be observed with other myotoxic substances (local anaesthetics such as bupivacaine or snake venoms). The results show that NCAM, PSA NCAM and desmin were already present on the first day after injury in the presumptive myoblasts. The highest level of all of these proteins was observed on the third day. At this stage, regenerating muscle fibers also strongly and diffusely expressed myosin heavy chain isoforms and utrophin throughout their sarcolemma, whereas MyoD1 expression was observed in the regenerating myonuclei. PSA NCAM and MyoD1 had gradually disappeared from the muscle fibers by the seventh day, by which time, the expression of the other developmentally regulated proteins had also decreased. On the 21st day after injury, a few fibers still expressed NCAM but not the other proteins. This study first shows that sodium dihydrogen phosphate is a new myotoxic agent that is cheap, widely available and easy to handle. It also establishes the schedule of expression of various developmentally regulated proteins in regenerating mouse muscle fibers.
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PMID:Sequence of expression of MyoD1 and various cell surface and cytoskeletal proteins in regenerating mouse muscle fibers following treatment with sodium dihydrogen phosphate. 1056 31

In the adult rodent brain, it is now well established that neurons are continuously generated from proliferating neuronal progenitor cells located in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus of the hippocampus. Recently, it has been shown that neurons can also be generated in vitro from various regions of the adult brain and spinal cord ventricular neuroaxis. As the highly polysialylated neural cell adhesion molecule (PSA-NCAM) has been shown to be specifically expressed by neuronal progenitor cells of the SVZ and the hippocampus, the present study was designed to determine whether cells expressing this molecule could be detected in the vicinity of the ventricular system of the adult rat brain and spinal cord. After double or triple immunostaining for different neuronal and glial markers, confocal microscopy was used to examine the surface of the ventricular neuroaxis in either 40- to 50-microm-thick transverse vibratome sections cut through different brain regions, or in 200- to 300-microm-thick tissue slices including the intact surface of the brain ventricles or of the spinal cord central canal. In untreated rats, PSA-NCAM, microtubule associated protein 2 (MAP2) and class III-beta-tubulin were found to be associated with a number of neuron-like cells located on the surface of the third and fourth ventricles and of the spinal cord central canal. The proliferation of the PSA-NCAM-immunoreactive (IR) neuron-like cells detected on the surface of the third and fourth ventricles was not affected by injection of epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) into these ventricles, but was stimulated by the combined injection of EGF + bFGF. These data indicate that cells exhibiting features of neuronal progenitors are present on the ependymal surface of the adult rat brain and spinal cord ventricular axis.
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PMID:Neuronal progenitor-like cells expressing polysialylated neural cell adhesion molecule are present on the ventricular surface of the adult rat brain and spinal cord. 1051 89

An immunohistochemical study was performed in order to evaluate the sequence of expression of various cell surface proteins [neural cell adhesion molecule (NCAM) and its polysialylated isoform, PSA NCAM, and utrophin], cytoskeletal proteins (myosin heavy chain isoforms, desmin) and the transcription factor MyoD1 in regenerating mouse muscle fibers following treatment with sodium dihydrogen phosphate. The sequence of the regeneration process with this new myotoxic agent is similar to that which can be observed with other myotoxic substances (local anaesthetics such as bupivacaine or snake venoms). The results show that NCAM, PSA NCAM and desmin were already present on the first day after injury in the presumptive myoblasts. The highest level of all of these proteins was observed on the third day. At this stage, regenerating muscle fibers also strongly and diffusely expressed myosin heavy chain isoforms and utrophin throughout their sarcolemma, whereas MyoD1 expression was observed in the regenerating myonuclei. PSA NCAM and MyoD1 had gradually disappeared from the muscle fibers by the seventh day, by which time, the expression of the other developmentally regulated proteins had also decreased. On the 21st day after injury, a few fibers still expressed NCAM but not the other proteins. This study first shows that sodium dihydrogen phosphate is a new myotoxic agent that is cheap, widely available and easy to handle. It also establishes the schedule of expression of various developmentally regulated proteins in regenerating mouse muscle fibers.
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PMID:Sequence of expression of MyoD1 and various cell surface and cytoskeletal proteins in regenerating mouse muscle fibers following treatment with sodium dihydrogen phosphate. 1045 Jul 94

Cerebral cortical dysplasia (CD) is a common cause of intractable childhood epilepsy. Five cases of CD were analyzed for GABA(A) receptor subunit beta (GABA(Abeta)), glutamate decarboxylase, AMPA receptor subunit 1 (GluR1) and subunit 2/3 (GluR2/3), and NMDA receptor 2 (NMDAR2) immunoreactivity. Antisera to the highly polysialylated neural cell adhesion molecule (PSA-NCAM) and human unc-33-like phosphoprotein 1 (hUlip 1) were used to identify neurons with 'developmentally immature' characteristics. Differences between CD and comparison tissue (n = 3) included: (1) prominent GABA(Abeta) immunoreactivity of the cytoplasm of dysmorphic neurons in the subcortical white matter and cortex in 1 CD case; (2) increased immunolabeling with anti-GluR1 and GluR2/3 antisera in dysmorphic neurons compared with more normal-appearing adjacent neurons and neurons from nondysplastic cortex; (3) varying numbers of cortical dysmorphic neurons stained for NMDAR2 in all 5 CD cases, in contrast to a complete lack of cellular immunoreactivity in 2/3 of the cases of nondysplastic cortex; (4) PSA-NCAM and hUlip 1 expression (usually observed only in populations of neurons that undergo axonal growth) was observed in CD tissue, but not in normal brain tissue. In summary, dysmorphic neurons in cases of CD have increased immunoreactivity for several excitatory neurotransmitter receptor subunits, show variable immunoreactivity for GABA(Abeta) and show expression of several proteins that are normally expressed only in immature neurons or those with the potential for synaptic plasticity.
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PMID:Cerebral cortical dysplasia: giant neurons show potential for increased excitation and axonal plasticity. 1057 49

Pituitary adenomas are usually benign neuroendocrine tumors. However, some of those that are histopathologically undistinguishable behave aggressively and metastasize. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is highly expressed during the development of the brain and pituitary, is detected in some neuroendocrine tumors and might be relevant as a prognostic marker in pituitary tumors. In the present study, we have searched for PSA-NCAM expression in four lineages of rat pituitary transplantable tumors (SMtTW). Each lineage, maintained by serial tumor grafts under the kidney capsule and skin, differed in its GH/Prl secretion, growth rate, and malignant behavior. PSA-NCAM expression, detected by immunohistochemistry and Western blotting and quantified by ELISA, varied according to the SMtTW lineage. The benign tumors, SMtTW2, with a low growth rate never expressed PSA-NCAM. Another benign lineage, SMtTW3, with a high growth rate expressed a low amount of PSA-NCAM. The highest PSA-NCAM expression was seen in tumors that grew beneath the skin, invaded the kidney, and metastasized (SMtTW4). Tumors of the SMtTW10 lineage, which behaved as either benign or malignant tumors, were heterogeneous in terms of PSA-NCAM expression. In this rat transplantable pituitary tumor model, PSA-NCAM expression correlated in decreasing order with: (a) invasiveness (P < 0.0001), (b) metastases (P = 0.004), (c) ability to grow under the skin (P = 0.006), and (d) growth rate under the kidney capsule (P < 0.01), but not with hormone secretion (r = 0.207). This model, which is very similar to the human pathology, suggests that PSA-NCAM evaluation is of interest in the diagnosis of malignancy and the prognosis of human pituitary tumors. In addition, the SMtTW tumors could be instrumental in evaluating the effects of new therapeutic agents modulating PSA-NCAM expression.
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PMID:Polysialylated-neural cell adhesion molecule expression in rat pituitary transplantable tumors (spontaneous mammotropic transplantable tumor in Wistar-Furth rats) is related to growth rate and malignancy. 1064 57


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