bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of exogenous ATP and related analogues on the proliferation rate of dissociated primary cultures of rat astrocytes
Authors: Ciccarelli R. , di Iorio P. , Ballerini P. , Ambrosini G. , Giuliani P. , Tiboni G. M. , Caciagli F. 
Published: January 2005

AbstractThe effects of ATP (5–500 μM) were evaluated on the proliferation rate of cultured astrocytes by measuring 3H‐thymidine incorporation and by flow cytometric analysis of the cell cycle. Determinations after 16 hours showed that ATP present in the culture medium for the whole period caused a dose‐dependent reduction of cell proliferation, while if the exposure to ATP was limited to the first 8 hours, the proliferation was increased (always in a dose‐dependent manner). A time course study of 3H‐thymidine incorporation showed that, in the presence of ATP, 3H‐thymidine was incorporated at a slower rate than in controls; the replacement of the culture medium with an ATP‐free fresh medium, at the 8th hour, was followed by a 3H‐thymidine incorporation occurring at such a fast rate to overshoot the control values. High performance liquid chromatography (HPLC) analysis, carried out to identify purine compounds present in the culture medium during cell exposure to ATP, indicated that more than 95% of the added ATP was metabolized within 1 hr. Conversely, an increase of purine metabolites was measured, this accumulation being greater at the highest concentrations of added ATP. The presence of high levels of extracellular ATP catabolites suggested that these compounds may act on the regulation of cell replication via the different purine receptors. This hypothesis was tested and confirmed by using agonists and antagonists selective for the P1 and the P2 sites. One hundred μM 2methylthio‐ATP (2MeSATP), a P2Y agonist metabolized as fast as ATP, reproduced effects very similar to the ATP‐induced ones. On the other hand, the nonhydrolisable ATP analogue, adenosine 5′‐(beta, gamma‐imido)‐triphosphate (AMP‐PNP) at 100 μM, induced a mitogenic effect as well as the A2 site stimulation. On the contrary, the activation of A1 receptors by 5 μM R‐phenyl‐isopropyladenosine (R‐PIA) inhibited astrocyte proliferation; moreover, 100 nM 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX), an A1 site antagonist, reversed the ATP‐induced inhibition of cell proliferation. These results indicate that exogenous ATP, as a consequence of its rapid extracellular breakdown, exerts a dual influence on astrocyte proliferation by the involvement of both P1 and P2Y receptors. These findings might be relevant to such pathological conditions of the central nervous system (CNS), as seizures, hypoxia or ischemia, in which great amounts of purines released in the brain can influence a reactive astrocyte proliferative response to injury. © 1994 Wiley‐Liss, Inc.
Differential expression of vomeromodulin and odorant‐binding protein, putative pheromone and odorant transporters, in the developing rat nasal chemosensory mucosae
Authors: Krishna N. S. Rama , Getchell M. L. , Margolis F. L. , Getchell Thomas V. 
Published: January 2005

AbstractExpression of the putative pheromone and odorant transporter, vomeromodulin, was characterized in developing rat nasal mucosae using in situ hybridization and immunocytochemistry. Initial expression of vomeromodulin mRNA and protein was detected at embryonic day (E)16 in the maxillary sinus component of the lateral nasal glands. The abundance of mRNA and protein in the lateral nasal glands increased with age and reached a peak at postnatal day (P)27. Also at P27, vomeromodulin mRNA and protein expression was initiated in vomeronasal glands and posterior glands of the nasal septum. Comparison of the developmental expression of odorant‐binding protein, another carrier protein synthesized in the lateral nasal glands, with that of vomeromodulin demonstrated major differences. In contrast to vomeromodulin, odorant‐binding protein was not detected until postnatal day 2 in the ventral component of the lateral nasal glands and anterior glands of the nasal septum. These results suggest that the expression of vomeromodulin and odorant‐binding protein is developmentally and differentially regulated and confirms the suggestion that vomeromodulin may function in olfactory and vomeronasal perireceptor processes as a transporter for pheromones and odorants. In addition, the embryonic expression of vomeromodulin suggests its involvement in olfactory perireceptor processes in utero. © 1995 Wiley‐Liss, Inc.
Peripheral myelin protein 22: Facts and hypotheses
Authors: Suter Ueli , Snipes G. J. 
Published: January 2005

AbstractMutations affecting the peripheral myelin protein 22 (PMP22) gene are associated with inherited motor and sensory neuropathies in mouse (Trembler and Trembler‐J) and human (Charcot‐Marie‐Tooth disease type 1A and Dejerine‐Sottas syndrome). Although genetic studies have established a critical role of PMP22 in the formation and/or maintenance of myelin in the peripheral nervous system, the biological function of PMP22 in myelin and in non‐myelin forming cells remains largely enigmatic. In this Mini Review, we will summarize the current knowledge about PMP22 and discuss its hypothetical function(s) in a broad context. © 1995 Wiley‐Liss, Inc.
Appearance of inducible nitric oxide synthase in the rat central nervous system after rabies virus infection and during experimental allergic encephalomyelitis but not after peripheral administration of endotoxin
Authors: Van Dam Anne‐Marie , Bauer J. , Man‐A‐Hing W. K. H. , Marquette C. , Tilders F. J. H. , Berkenbosch F. 
Published: January 2005

AbstractThe cellular localization of inducible (iNOS) and constitutive (cNOS) nitric oxide synthase was studied in rats by immunocytochemical techniques involving specific iNOS and cNOS directed antibodies and by NADPH‐diaphorase histochemistry. Paraformaldehyde‐fixed vibratome sections of brains and cryostat sections of peripheral lymph nodes were studied of rats treated with endotoxin (2.5 μg/kg or 2.5 mg/kg i.v.), rats infected with rabies virus, and rats exposed to experimental allergic encephalomyelitis (EAE). Endotoxin‐treated animals showed no appearance of immunoreactive iNOS (ir‐iNOS) cells in the brain with the exception of a few microglial cells near the median eminence and some meningeal macrophages. In the same animals however, iNOS‐immunoreactive cells were found in peripheral lymph nodes. Neurons that stain positive for cNOS and for NADPH‐diaphorase could be observed in brains of control as well as of endotoxin‐treated animals with a similar distribution and staining intensity. In contrast, animals that had been infected with rabies virus or subjected to EAE, showed the appearance of ir‐iNOS‐positive cells in several brain areas. These cells are located near blood vessels and lesion sites. The majority of these cells are GSA‐I‐B4 isolectin‐positive and therefore are likely to represent macrophages. Our data suggest that increased production of nitric oxide may play a role in the altered brain functions in rabies‐infected and EAE rats. On the contrary, increased nitric oxide production is probably not involved in the non‐specific symptoms of sickness induced by endotoxin. © 1995 Wiley‐Liss, Inc.
Proliferative capacity of oligodendrocytes in the demyelinating twitcher spinal cord
Authors: Taniike M. , Suzuki Kinuko 
Published: January 2005

AbstractThe proliferative capacity of oligodendrocytes was investigated in the spinal white matter of the twitcher mouse, a murine model of a genetic demyelinating disease globoid cell leukodystrophy (GLD), in which degeneration of oligodendrocytes due to metabolic perturbation has been well documented. In normal mice at 30 and 45 days of age, proliferating cells labeled with 5‐bromo‐2′‐deoxyuridine (BrdU) were scarce, and the majority of BrdU‐labeled cells did not immunostain with antibodies for oligodendrocytes, astrocytes, or microglia/macrophages. Only a few cells with markers for oligodendrocytes, carbonic anhydrase (CA), or the Pi form of glutathione‐S‐transferase (Pi), were labeled with BrdU. In the twitcher spinal cord, total numbers of BrdU‐labeled cells were almost 6 times that of the normal littermate mice at 30 days of age, and 28 times at 45 days of age. However, this increase was largely due to an increase of cells labeled with F4/80, a marker for the microglia/macrophages. CA or Pi positive cells only constituted less than 10% of all labeled cells. With progression of demyelination from 30—45 days, total numbers of CA positive or Pi positive oligodendrocytes decreased, but percentages of cells double‐labeled with BrdU and CA or Pi remained fairly constant. The results indicated that oligodendrocytes proliferated, to some extent, in the twitcher despite the genetic metabolic defect, and their decrease in number with progression of disease was not due to declined proliferation but rather cellular degeneration as the result of an intrinsic metabolic perturbation. © 1995 Wiley‐Liss, Inc.
PKA and PKC activation induces opposite glial fibrillary acidic protein (GFAP) expression and morphology changes in a glioblastoma multiform cell line of clonal origin
Authors: Arcuri Cataldo , Bocchini V. , Guerrieri P. , Fages C. , Tardy M. 
Published: January 2005

AbstractPossible differentiation mechanisms were investigated in a glioblastoma multiform cell line (GL15) presenting an undifferentiated phenotype with weak glial fibrillary acidic protein (GFAP) and strong vimentin (VIM) expression. Serum‐free conditions induced time‐dependent increases of GFAP‐mRNA and GFAP protein levels, associated with a process‐bearing astrocytic morphology.Activation of protein kinase C (PKC) by tumor promoter phorbol 12‐myrystate 13‐acetate (PMA) induced a rapid morphological differentiation and a decrease in GFAP mRNA, whereas the GFAP level remained unchanged. Such parameters were shown to characterize a physiological differentiation stage in astroglial cultures. Treatment of process‐bearing GL15 cells with dibutyryl cyclic AMP (dbcAMP), a protein kinase A (PKA) activator, induced a timedependent decrease in the GFAP mRNA and GFAP protein levels and reverted morphological changes induced by serum‐free conditions. Neither PMA nor dbcAMP influenced the VIM mRNA expression.In GL15 cells, PKC and PKA activation have opposite effects. Understanding the role of these kinases in malignant transformation and in the in vitro differentiation process is of both basic and clinical interest. © 1995 Wiley‐Liss, Inc.
Cryogenic spinal cord injury induces astrocytic gene expression of insulin‐like growth factor I and insulin‐like growth factor binding protein 2 during myelin regeneration
Authors: Yao Da‐Lin , West N. R. , Bondy C. A. , Brenner M. , Hudson L. D. , Zhou J. , Collins G. H. , Webster H. deF. 
Published: January 2005

AbstractTo study injury‐induced astrocytic responses associated with regrowth of axons and regeneration of myelin, the method of Collins and colleagues was used to make focal cryogenic lesions in spinal cords of adult rats (Collins et al.: J Neuropathol Exp Neurol 45:742–757, 1986). The duration of cryogenic injury (CI), the size of the cryode, and its temperature were chosen to destroy all myelin sheaths and axons without producing cavities or hemorrhages. Messenger RNA and peptide distributions of insulin‐like growth factor I (IGF‐I), IGF‐I receptor (IGFR‐I), IGF binding protein 2 (IGFBP‐2), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP) were studied 3–56 days after CI by in situ hybridization and immunocytochemistry. At 3 days, vimentin‐positive, GFAP‐negative astrocyte‐Iike cells in the lesion expressed IGF‐I mRNA and peptide and 7 days after CI, both were expressed by typical GFAP‐positive, hypertrophic astrocytes, many of which also were vimentin‐positive. Levels of IGF‐I, IGFBP‐2, and GFAP mRNA and peptide were higher in lesion astrocytes after 14 days. They attained maximum levels at 21–28 days before declining to near control levels at 56 days. Decreasing relative levels of oligodendroglial MBP mRNA were found in and around lesions 7–14 days after CI; subsequently, rising levels accompanied remyelination. At 28 and 56 days after CI, some transferrin‐positive, oligodendroglia‐like cells also were immunostained by anti‐IGFR‐I. Our findings suggest that early astrocytic production of IGF‐I and IGFBP‐2 may be involved in the myelin regeneration which occurs in this model of spinal cord injury. © 1995 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Heterogeneity of human neuroblastoma cell lines in their proliferative responses to basic FGF, NGF, and EGF: Correlation with expression of growth factors and growth factor receptors
Authors: Janet T. , Lüdecke G. , Otten U. , Unsicker Klaus 
Published: January 2005

AbstractGrowth factors can induce both proliferation or differentiation of neuroblastoma (NB) cells through interaction with specific receptors. Using two automated colorimetric assays for determinations of cell numbers, the present study demonstrates that (a) different NB and neuroepithelioma cell lines show distinct responses, both qualitatively and quantitatively, to basic FGF (bFGF), NGF, and EGF(b) even closely related NB cell lines (e.g., SK‐N‐SH, SH‐SY5Y, and SHEP) do not respond uniformly to these factors; c) responses of the two neuroepithelioma cell lines employed (SK‐N‐MC and CHP‐100) differ, but match those of certain NB cell lines; and d) two growth factors, bFGF and EGF, may both stimulate or inhibit proliferation, depending on the cell line studied. Specifically, IMR‐32, SK‐N‐SH, and SH‐SY5Y showed a mitogenic response to each growth factor. Maximal proliferative responses ranged from 204–355% as compared to controls (100%). GICAN was stimulated by NGF (199%), and SK‐N‐MC and NMB by EGF (282 and 140%, respectively), but other factors were ineffective. CHP‐100 and GIMEN were inhibited by bFGF. NGF and EGF were not effective on CHP‐100 cells, while EGF caused an arrest of mitogenic activity in GIMEN cells, and NGF stimulated their proliferation. Cell lines SHEP and LAN1 did not respond to any factor. To begin to analyze putative relationships of growth factor responsiveness and growth factor/growth factor receptor expressions, IMR‐32, GIMEN, and LAN1 cell lines were studied for the presence of bFGF, NGF, FGF receptors (R)‐1 (flg) and FGFR‐4, trk, and low‐affinity NGF receptor (p75) mRNAs. All three cell lines expressed bFGF and NGF mRNA, but not the FGFR‐1, FGFR‐4, trk, and p75 mRNAs. These results suggest extremely diverse patterns of NB/neuroepithelioma cell responsiveness to “mitogenic” growth factors and no overt correlation between such responses and growth factor/growth factor receptor expression. © 1995 Wiley‐Liss, Inc.
Effects of growth factors on phosphatidylinositol‐3 kinase in astroglial cells
Authors: Pomerance Martine , Gavaret J.‐M. , Breton M. , Pierre M. 
Published: January 2005

AbstractGrowth factors differently regulate astroglial cell differentiation and proliferation. In an effort to understand the early intracellular events promoted by growth factors in astroglial cells, we have determined the effects of insulin‐like growth factor I (IGF1), insulin, platelet‐derived growth factor (PDGF), epidermal growth factor (EGF) and fibroblast growth factors (FGFs) on phosphatidylinositol‐3 kinase (PI(3)‐kinase).In astroglial cells cultured in serum‐free medium, IGF1, PDGF, and EGF, which stimulate cell proliferation, increased PI(3)‐kinase activity immunoprecipitated with anti‐phosphotyrosine antibodies as shown by thin layer chromatography and high performance liquid chromatography. FGFa and FGFb, which strongly stimulate proliferation, glutamine synthetase, and deiodinase activities and modify cell morphology, have no effect on PI(3)‐kinase activity. Addition of 1 nM PDGF, 10 nM IGF1, or 100 nM EGF to the culture medium rapidly stimulated PI(3)‐kinase activity which declined slowly after 2 min. The stimulation of PI(3)‐kinase increased with growth factor concentration. The maximum increase in PI(3)‐kinase activity occurred with 50 nM IGF1, 1 nM PDGF, or 100 nM EGF. Since insulin was active only at high concentration (1 μM), its effect was probably mediated through IGF1 receptors and not through IGF1 receptors and not through insulin receptors.IGF1 and PDGF, to a lesser degree, also increased the PI(3)‐kinase activity associated with pp60c‐src protein. Immunoblots performed with an antibody directed against the p85‐subunit of the PI(3)‐kinase confirmed that IGF1 increased the number of PI(3)‐kinase molecules associated with phosphotyrosine‐containing proteins or with c‐src protein.Each growth factor affects in a different manner the association of PI(3)‐kinase with phosphotyrosine‐containing proteins and with pp60c‐src and thus probably modulates intracellular signals downstream of PI(3)‐kinase in astroglial cells. © 1995 Wiley‐Liss, Inc.
Macrophage inflammatory protein 1‐α mRNA expression in an immortalized microglial cell line and cortical astrocyte cultures
Authors: Murphy Greer , Jia X.‐C. , Song Y. , Ong E. , Shrivastava R. , Bocchini V. , Lee Y. L. , Eng L. F. 
Published: January 2005

AbstractMacrophage inflammatory protein 1 (MIP‐1) is a recently characterized inflammatory and chemokinetic cytokine. Proinflammatory stimuli have been shown to induce expression of MIP‐1 by macrophages. We hypothesized that microglia and astrocytes express MIP‐1α because of their many immunologic similarities to macrophages. MIP‐1α mRNA was examined with quantitative reverse transcription and polymerase chain reaction in an immortalized mouse microglial cell line (BV‐2) and in mouse cortical astrocyte cultures. We found that in both the BV‐2 microglial cell line and in astrocyte cultures, MIP‐1α mRNA was strongly induced by lipopolysaccharide and the phorbol ester PMA. MIP‐1α mRNA was reduced by dBcAMP, interferon‐γ, and PGE1. Dexamethasone decreased MIP‐1α mRNA levels in astrocyte cultures, but not in BV‐2 microglial cells. Interleukin‐1β, tumor necrosis factor α and MIP‐1α had no effect on MIP‐1α mRNA is expression. These findings demonstrate that MIP‐1α mRNA is expressed by cultured glial cells and is regulated by proinflammatory and anti‐inflammatory stimuli. MIP‐1α may be expressed by microglia and astrocytes in vivo, and may help modulate cerebral inflammation. © 1995 Wiley‐Liss, Inc.
Modulatory actions of gamma aminobutyric acid (GABA) on GABA type a receptor subunit expression and function
Authors: Schousboe A. , Redburn D. A. 
Published: January 2005

AbstractGamma aminobutyric acid (GABA) is present in the central nervous system (CNS) during very early embryogenesis. It is therefore likely to play a role not only as a neurotransmitter but also as a signal molecule for neuronal differentiation, growth, and development. It has been firmly established that formation of synapses is strengthened by GABA, and the expression of certain subunits of the GABA type A (GABAA) receptor complex is clearly promoted by GABA. This latter effect of GABA may have profound implications for the functional activity of GABAergic synapses since the pharmacological properties of GABAA receptors are governed by the subunit composition of the receptor complex. Dynamic changes in GABAA receptor expression and diversity during development and differentiation may therefore play important roles for the inhibitory potential of the CNS during mature stages. © 1995 Wiley‐Liss, Inc.
Gene expression and oligodendrocyte development in the myelin deficient rat
Authors: Nadon N. L. , Duncan I. D. 
Published: January 2005

AbstractThe proteolipid proteins play a major role in the structure of the CNS myelin sheath, but they have also been implicated in the oligodendrocyte development leading to myelination. Mutations in the PLP gene result in severe dysmyelination and a paucity of mature oligodendrocytes. The myelin deficient (md) rat, carrying a Thr75? Pro substitution present in both isoforms of proteolipid protein (PLP and DM20), is the most severely affected of the PLP mutants described to date. The expression of myelin associated genes was quantitated to determine the effect of the mutation on oligodendrocyte development in vivo. At 5 days postnatal, gene expression in the and rat approximated that in age‐matched control rats, but as they matured, there was a progressive inhibition of gene expression in the and rats. The genes expressed late in the myelination program (PLP and MBP) were affected more dramatically than those expressed earlier in oligodendrocyte development (CNP and GPDH). The results indicate that the later stages of oligodendrocyte maturation and myelin elaboration are inhibited. © 1995 Wiley‐Liss, Inc.
Brain distribution of four rat homologues of the drosophila dunce cAMP phosphodiesterase
Authors: Engels P. , Abdel'Al S. , Hulley P. , Lübbert Hermann 
Published: January 2005

AbstractWe have analyzed the brain distribution of the rat cAMP‐specific phosphodiesterases (rPDEIV) which are closely related to the defective gene products of the drosophila melanogaster learning and memory mutant dunce. PCR analysis of rat brain cDNA was performed on the four known dunce‐like cAMP PDE rat isogenes (rPDE‐IV‐A, ‐B, ‐C, ‐D). High expression of three of these isogenes (rPDEIV‐A, ‐B, ‐D) highlighted their involvement in regulation of cAMP in the brain. Specific probes for all four isogenes were then used for in situ hybridization of rat brain sections. Distinct but overlapping expression patterns were observed for rPDEIV‐A, rPDEIV‐B, and rPDEIV‐D. Abundant expression of these subtypes was observed in the olfactory system, the hippocampus and the cerebellum, while no specific signals could be detected in most areas of the brain for the subtype rPDEIV‐C. © 1995 Wiley‐Liss, Inc.
Experimental strategies to promote central nervous system remyelination in multiple sclerosis: Insights gained from the Theiler's virus model system
Authors: Miller D. J. , Asakura K. , Rodriguez M. 
Published: January 2005

AbstractThe Destruction of central nervous system (CNS) myelin, the lipid‐rich insulator surrounding axons in the mammalian brain and spinal cord, is the primary pathological finding in multiple sclerosis. Myelin loss can result in a significant clinical deficit, and was originally thought to be permanent, similar to axonal destruction. However, myelin regeneration is now an established phenomenon in both human disease and animal models of CNS demyelination. In this review, the concept of remyelination in demyelinating deseases such as multiple sclerosis is discussed and the usefulness of animal models of CNS demyelination in developing experimental strategies to promote remyelination is examined Special emphasis is given to the Theiler's murine encephalomyelitis model, which has been the primary animal model used to investigate therapies designed specifically to stimulate myelin repair. © 1995 Wiley‐Liss, Inc.