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

In the central nervous system cell migration is usually restricted to developmental periods and occurs mainly radially, following the radial glia. Nevertheless, in the subependymal layer of the adult rodent forebrain tangential migration of newly generated neuronal precursors directed to the olfactory bulb, which follow a well-defined pathway without dispersion, has been recently demonstrated. In the present study, by using light microscopic immunocytochemistry for glia-associated antigens (glial fibrillary acidic protein, S-100 and vimentin), and conventional electron microscopy, we observed a dense mesh-work of astrocytic cells and processes throughout the subependymal layer of the adult rat. These cells were organized to form tangentially oriented glial tubes in the subependymal layer of the lateral ventricle and in its rostral extension to the olfactory bulb. Glial tubes were particularly evident within the rostral extension and were widely intercommunicating. Using markers for the proliferating/ migrating cells of the rostral migratory stream (5-bromo-2'-deoxyuridine, PSA-NCAM, class III beta-tubulin), we provide evidence that long chains of PSA-NCAM/beta-tubulin-positive, newly generated cells are consistently observed inside the glial tubes. These results demonstrate the existence of a peculiar glial organization within the subependymal layer of the adult rat, consisting of long astrocytic tubes that likely represent a new type of glial guidance, accounting for the tangential migration of a high number of cells along their restricted pathway, to the olfactory bulb.
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PMID:Glial tubes in the rostral migratory stream of the adult rat. 897 30

The adult mammalian subventricular zone (SVZ) contains stem cells that give rise to neurons and glia. In vivo, SVZ progeny migrate 3-8 mm to the olfactory bulb, where they form neurons. We show here that the SVZ of the lateral wall of the lateral ventricles in adult mice is composed of neuroblasts, glial cells, and a novel putative precursor cell. The topographical organization of these cells suggests how neurogenesis and migration are integrated in this region. Type A cells had the ultrastructure of migrating neuronal precursors. These cells were arranged as chains parallel to the walls of the ventricle and were polysialylated neural adhesion cell molecule- (PSA-NCAM), TuJ1- (beta-tubulin), and nestin-positive but GFAP- and vimentin-negative. Chains of Type A cells were ensheathed by two ultrastructurally distinct astrocytes (Type B1 and B2) that were GFAP-, vimentin-, and nestin-positive but PSA-NCAM- and TuJ1-negative. Type A and B2 (but not B1) cells incorporated [3H]thymidine. The most actively dividing cell in the SVZ corresponded to Type C cells, which had immature ultrastructural characteristics and were nestin-positive but negative to the other markers. Type C cells formed focal clusters closely associated with chains of Type A cells. Whereas Type C cells were present throughout the SVZ, they were not found in the rostral migratory stream that links the SVZ with the olfactory bulb. These results suggest that chains of migrating neuroblasts in the SVZ may be derived from Type C cells. Our results provide a topographical model for the adult SVZ and should serve as a basis for the in vivo identification of stem cells in the adult mammalian brain.
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PMID:Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. 918 42

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 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

Effective cell replacement therapies for neurological disease require neuron-restricted precursors as grafted cells. The problem of obtaining sufficient grafts for transplantation can be resolved by creating an appropriate immortalized cell line. In the present study, a thermally controlled immortalized GABAergic neuronal progenitor cell line (RMNE6) was established from E13 rat ventral mesencephalon cells immortalized using the temperature-sensitive mutant of SV40 large T antigen (ts-TAg). RMNE6 cells proliferated rapidly and expressed a neuron-like phenotype at the permissive temperature (33 degrees C), but eventually stopped growing at the non-permissive temperature (39 degrees C). Expression of the neuronal markers PSA-NCAM, beta-tubulin III and MAP2 by RMNE6 cells was confirmed by RT-PCR or immunocytochemistry. Furthermore, these cells exhibited functional GABAergic neuron properties, as evidenced by the expression of glutamate decarboxylase (GAD) as well as the synthesis and release of the neurotransmitter GABA in a calcium-dependent manner. Moreover, RMNE6 cells spontaneously expressed and secreted several neurotrophic factors, such as NGF, BDNF, NT-3, NT-4/5, and GDNF. The cells survived well and kept expression of SV40 Tag, GAD65/67 and GABA in the striatum, at least 28 days after being transplanted in the rat brain. Tumorigenesis assays confirmed the safety of the immortalized cell line in vivo. Taken together, the results support the use of RMNE6 cells as an ideal cell model for transplantation research aimed at the treatment and prevention of neurodegenerative disease.
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PMID:Establishment of an immortalized GABAergic neuronal progenitor cell line from embryonic ventral mesencephalon in the rat. 1840 53

Deep-brain lacunar infarct represents a significant clinical problem as it produces severe symptoms highly resistant to rehabilitation. The limited area of necrosis may facilitate neurorepair via the action of various novel neuroprotective strategies including cell-based therapies. The lesion was induced by stereotactic injection of ouabain into adult rat brains. Subsequent behavioral testing involved beam walking task, rotarod, visual discrimination task and apomorphine rotation. For morphological and topographical analysis brain slices were stained with H-E and evaluated under light microscopy. Lesion size was measured in absolute terms and in relation to the whole brain volume. Immunohistochemical analysis for the co-localization of BrdU with specific cell-type markers (PSA-NCAM, NG2, beta-tubulin III, GFAP, ED1) have has been performed, to determine the fate of newly generated cells with emphasis on evidence of neurogenesis. The lesion involved the basal ganglia, basal forebrain nuclei, internal capsule and striatum (just 1-2% of total brain volume). Significant and relatively stable behavioral deficits were observed up to 30 days. Furthermore, large numbers of cells are seen to be newly generated in response to injury with a significant proportion of these being present on account of neurogenesis.
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PMID:Structural and functional characteristic of a model for deep-seated lacunar infarct in rats. 1865 34

NG2 cells express the chondroitin sulfate proteoglycan NG2 and are a fourth type of glia distinct from astrocytes, oligodendrocytes, and microglia. NG2 cells generate oligodendrocytes but have also been reported to represent neuronal progenitor cells in the postnatal mouse subventricular zone (SVZ). We performed a detailed immunohistochemical analysis of NG2 cells in the mouse SVZ, rostral migratory stream (RMS), and olfactory bulb granule cell layer (OB GCL), which constitute a neurogenic niche in the postnatal forebrain. NG2 cells in the SVZ and RMS expressed the oligodendrocyte precursor cell antigen platelet-derived growth factor receptor-alpha but did not express antigens known to be expressed by neuronogenic cells in the SVZ, such as doublecortin, PSA-NCAM, beta-tubulin, Dlx2, or GFAP. More than 99.5% of the proliferating cells in the SVZ were NG2 negative. In the olfactory bulb, NG2 cells were found to generate primarily oligodendrocytes and a small number of astrocytes but not neurons. In the SVZ and RMS, NG2 cells were sparse and made up a much smaller fraction of the cells compared with the surrounding nonneurogenic parenchyma. Parenchymal NG2 cells were often located along the border of the SVZ and RMS. The abundance of NG2 cells increased in the distal parts of the RMS and especially in the OB GCL, where NG2 cell processes were seen in close proximity to many maturing interneurons. Our findings indicate that NG2 cells do not represent neuronal progenitor cells in the postnatal SVZ but are likely to be oligodendrocyte precursor cells.
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PMID:NG2 cells are distinct from neurogenic cells in the postnatal mouse subventricular zone. 1905 88

Recently we showed Lupeol, a triterpene, found in fruits and vegetables inhibits the growth of tumors originated from human androgen-sensitive prostate cancer (CaP) cells and decreases the serum-PSA levels in a mouse model. Here, we provide evidence that Lupeol inhibits the growth of androgen-sensitive as well as androgen-insensitive CaP cells by inducing G2/M cell cycle arrest without exhibiting any toxicity to normal human prostate epithelial cells (PrEC) at the doses at which it kills cancer cells. We observed that Lupeol treatment to LNCaP and DU145 cells resulted in a dose-dependent (i) decrease in the protein levels of Cyclins-A, -B1, -D1, -D2, -E2, cyclin-dependent kinase (cdk)-2 and (ii) increase in the protein level of CDK-inhibitor p21. Since G2/M cell cycle phase is regulated by microtubule assembly, we investigated effect of Lupeol on microtubule assembly, its regulation and down-stream targets in CaP cells. Lupeol treatment significantly modulated the level of (i) microtubule components alpha-tubulin and beta-tubulin, (ii) microtubule-regulatory protein stathmin, and (iii) microtubule-regulatory down-stream target/pro-survival protein survivin. Lupeol treatment also decreased the level of anti-apoptotic protein cFLIP. Finally, Lupeol was observed to significantly decrease the transcriptional activation of survivin and cFLIP genes in CaP cells. We conclude that the Lupeol-induced growth inhibition of CaP cells is a net outcome of simultaneous effects on stathmin, cFLIP, and survivin which results in the disruption of microtubule assembly. We suggest that Lupeol alone or as an adjuvant to other microtubule agents could be developed as a potential agent for the treatment of human CaP.
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PMID:Lupeol triterpene, a novel diet-based microtubule targeting agent: disrupts survivin/cFLIP activation in prostate cancer cells. 1968 15