bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleotide‐mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors
Authors: Fumagalli Marta , Brambilla Roberta , D'Ambrosi Nadia , Volonté Cinzia , Matteoli Michela , Verderio Claudia , Abbracchio Maria P. 
Published: July 2003

AbstractATP is the dominant messenger for astrocyte‐to‐astrocyte calcium‐mediated communication. Definition of the exact ATP/P2 receptors in astrocytes and of their coupling to intracellular calcium ([Ca2+]i) has important implications for brain physiology and pathology. We show that, with the only exception of the P2X6 receptor, primary rat cortical astrocytes express all cloned ligand‐gated P2X (i.e., P2X1–5 and P2X7) and G‐protein‐coupled P2Y receptors (i.e., P2Y1, P2Y2, P2Y4, P2Y6, and P2Y12). These cells also express the P2Y‐like UDP‐glucose receptor, which has been recently recognized as the P2Y14 receptor. Single‐cell image analysis showed that only some of these receptors are coupled to [Ca2+]i. While ATP induced rapid and transient [Ca2+]i increases (counteracted by the P2 antagonists suramin, pyridoxal‐phosphate‐6‐azophenyl‐2′‐4′‐disulfonic acid and oxidized ATP), the P2X1/P2X3 agonist αβmeATP produced no changes. Conversely, the P2X7 agonist BzATP markedly increased [Ca2+]i; the presence and function of the P2X7 receptor was also confirmed by the formation of the P2X7 pore. ADP and 2meSADP also produced [Ca2+]i increases antagonized by the P2Y1 antagonist MRS2179. Some cells also responded to UTP but not to UDP. Significant responses to sugar‐nucleotides were also detected, which represents the first functional response reported for the putative P2Y14 receptor in a native system. Based on agonist preference of known P2 receptors, we conclude that, in rat astrocytes, ATP‐induced calcium rises are at least mediated by P2X7 and P2Y1 receptors; additional receptors (i.e., P2X2, P2X4, P2X5, P2Y2, P2Y4, and P2Y14) may also contribute. © 2003 Wiley‐Liss, Inc.
Expression and regulation of L‐cystine transporter, system xc−, in the newly developed rat retinal Müller cell line (TR‐MUL)
Authors: Tomi Masatoshi , Funaki Takeshi , Abukawa Hayato , Katayama Kazunori , Kondo Tetsu , Ohtsuki Sumio , Ueda Masatsugu , Obinata Masuo , Terasaki Tetsuya , Hosoya Ken‐Ichi 
Published: July 2003

AbstractThe purpose of the present study was to elucidate the expression and regulation of the L‐cystine transporter, system xc−, in Müller cells. In this study, newly developed conditionally immortalized rat Müller cell lines (TR‐MUL) from transgenic rats harboring the temperature‐sensitive SV 40 large T‐antigen gene were used as an in vitro model. TR‐MUL cells express large T‐antigen and grow well at 33°C with a doubling time of 30 h, but do not grow at 39°C. TR‐MUL cells express typical Müller cell markers such as S‐100, glutamine synthetase, and EAAT1/GLAST, whereas EAAT2/GLT‐1 and EAAT5 are not detected. TR‐MUL cells also exhibit little or no expression of glial fibrillary acidic protein. We found that TR‐MUL5 cells exhibited [14C]L‐cystine uptake activity and expressed xCT and 4F2hc, which involve system xc−. The uptake of [14C]L‐cystine was significantly inhibited by L‐glutamic acid and L‐aspartic acid, whereas L‐leucine had no effect. Following diethyl maleate (DEM) treatment, the glutathione concentration in TR‐MUL5 cells was reduced in the first 24 h, then gradually recovered for more than 24 h. The L‐cystine uptake rate and the xCT expression level in TR‐MUL5 cells were enhanced by DEM treatment. In contrast, the 4F2hc expression level was unchanged. In conclusion, TR‐MUL cells have the properties of Müller cells and exhibit system xc−‐mediated L‐cystine uptake activity. The oxidative stress conditions following DEM treatment activate L‐cystine transport in TR‐MUL cells due to the enhanced transcription of the xCT gene. GLIA 9999:000–000, 2003. © 2003 Wiley‐Liss, Inc.
Evidence for astrocyte heterogeneity: A distinct subpopulation of protoplasmic‐like glial cells is detected in transgenic mice expressing Lmo1‐lacZ
Authors: Scotti Campos Lia 
Published: July 2003

AbstractThe adult mammalian central nervous system (CNS) contains a large number of different cell types, which arise from the ventricular (VZ) and subventricular zones during embryonic development. In this study, we used a transgenic mouse expressing Lmo1‐LacZ from a randomly inserted promoter/reporter gene construct to identify a glial subpopulation. LMO1 is an LIM domain‐containing protein, thought to act in protein‐protein interactions. We found first that in the adult transgenic CNS, β‐galactosidase (β‐gal) was expressed in a specific subpopulation of protoplasmic‐like cells, which did not express detectable levels of glial fibrilary acidic protein unless a lesion was produced. Secondly, during development, β‐gal+ cells were found arising from discrete regions of the VZ. Taken together, these results identify a subpopulation of protoplasmic glial cells in the adult CNS and suggest that they arise from a restricted VZ region during CNS development. © 2003 Wiley‐Liss, Inc.
Essential role for ERK mitogen‐activated protein kinase in matrix metalloproteinase‐9 regulation in rat cortical astrocytes
Authors: Arai Ken , Lee Sun‐Ryung , Lo Eng H. 
Published: July 2003

AbstractMatrix metalloproteinases (MMPs) contribute to the pathophysiology of brain injury and inflammation but little is known about their regulatory signaling pathways in brain cells. Here we examine the role of mitogen‐activated protein (MAP) kinase pathways in MMP‐9 regulation in cortical rat astrocytes. The protein kinase C (PKC) activator phorbol 12‐myristate 13‐acetate (PMA) induced MMP‐9 but not MMP‐2 secretion as measured by gelatin zymography. Northern blot and RT‐PCR analysis showed that MMP‐9 responses occurred at the mRNA level. Although PMA increased phosphorylation in all three major MAP kinase pathways (ERK, p38 MAP kinase, and JNK), only inhibition of the ERK pathway by the MEK/ERK inhibitor U0126 (0.1–10 μM) significantly reduced MMP‐9 upregulation, even when treatment was delayed for 4 h after PMA exposure. Inhibitors of p38 MAP kinase (SB203580) and JNK (SP600125) had no effect. This PKC pathway was compared to a cytokine response by exposing astrocytes to TNFα, which also activated MAP kinase and induced MMP‐9 upregulation. But in this case, all three MAP kinase inhibitors (U0126, SB203580, and SP600125) reduced TNFα‐induced MMP‐9 upregulation. Taken together, these results suggest that the ERK MAP kinase is essential for MMP‐9 upregulation via PKC and cytokine pathways in astrocytes. © 2003 Wiley‐Liss, Inc.
Cultured astrocytes express toll‐like receptors for bacterial products
Authors: Bowman Christal C. , Rasley Amy , Tranguch Susanne L. , Marriott Ian 
Published: July 2003

AbstractIt has become apparent that astrocytes may be important contributors to inflammatory immune responses within the brain in response to microbial challenges. To date, the mechanisms that underlie activation of this major glial cell type by such challenges have not been investigated. In the present study, we present evidence for members of a recently discovered family of receptors for highly conserved microbial components, the Toll‐like receptors (TLRs), in isolated cultures of primary murine astrocytes. We describe the low‐level constitutive expression of messenger RNA‐encoding TLR2, TLR4, TLR5, and TLR9 in resting cultures of these cells. Importantly, the level of expression of messenger RNA for each of these receptors is markedly elevated following exposure to specific bacteria‐derived ligands for these receptors. The functional expression of these receptor proteins is further supported by the ability of known ligands for each TLR to induce both message expression and protein secretion of the proinflammatory cytokine, interleukin‐6. In addition, the recent availability of antibodies to TLR2 and TLR4 has enabled us to demonstrate directly the presence of these receptors on astrocytes by Western blot and immunofluorescence analysis, respectively. Furthermore, we have confirmed the sensitivity of such receptor expression to ligand stimulation. The present demonstration of Toll‐like microbial pattern‐recognition receptors on primary astrocytes provides a mechanistic link between bacterial challenge and inflammatory immune responses that may be an important component of the pathologies of bacterially induced inflammatory CNS disorders. © 2003 Wiley‐Liss, Inc.
Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium
Authors: Stout Charles , Charles Andrew 
Published: July 2003

AbstractThe extracellular concentrations of Ca2+ and Mg2+ are well known to play important roles in the function of the central nervous system. We examined the effects of extracellular Ca2+ and Mg2+ on ATP release and intercellular signaling in astrocytes. The extent of propagation of intercellular Ca2+ waves evoked by mechanical stimulation was increased by reduction of extracellular Ca2+ ([Ca2+]o) or Mg2+ concentration ([Mg2+]o) and was decreased by elevated [Mg2+]o. Reduction of extracellular Ca2+ concentration ([Ca2+]o) evokes intercellular Ca2+ signaling in astrocytes; a similar effect was observed in response to change from 5 mM [Mg2+]o to 0 [Mg2+]o. Release of low‐molecular‐weight dyes and ATP was also activated by low [Ca2+]o or [Mg2+]o and inhibited by high [Ca2+]o or [Mg2+]o. Astrocytes showed low [Ca2+]o–activated whole cell currents consistent with currents through connexin hemichannels. These currents were inhibited by extracellular Mg2+. We conclude that extracellular divalent cations modulate intercellular Ca2+ signaling in astrocytes by modulating the release of ATP, possibly via connexin hemichannels. © 2003 Wiley‐Liss, Inc.
Phagocytosis of apoptotic inflammatory cells by microglia and its therapeutic implications: Termination of CNS autoimmune inflammation and modulation by interferon‐beta
Authors: Chan Andrew , Seguin Rosanne , Magnus Tim , Papadimitriou Christina , Toyka Klaus V. , Antel Jack P. , Gold Ralf 
Published: July 2003

AbstractApoptosis of autoaggressive T‐cells in the CNS is an effective, noninflammatory mechanism for the resolution of T‐cell infiltrates, contributing to clinical recovery in T‐cell‐mediated neuroinflammatory diseases. The clearance of apoptotic leukocytes by tissue‐specific phagocytes is critical in the resolution of the inflammatory infiltrate and leads to a profound downregulation of phagocyte immune functions. Adult human microglia from surgically removed normal brain tissue was used in a standardized, light‐microscopic in vitro phagocytosis assay of apoptotic autologous peripheral blood‐derived mononuclear cells (MNCs). Microglia from five different patients had a high capacity for the uptake of apoptotic MNCs in contrast to nonapoptotic target cells with the phagocytosis rate for nonapoptotic MNCs amounting to only 61.6% of the apoptotic MNCs. A newly described phosphatidylserine receptor, critical in the phagocytosis of apoptotic cells by macrophages, is also expressed at similar levels on human microglia. The effects of the therapeutically used immunomodulatory agent interferon‐beta (IFNβ) were investigated using Lewis rat microglia and apoptotic, encephalitogenic, myelin basic protein‐specific autologous T‐cells. Also, rat microglia had a high capacity to phagocytose apoptotic T‐cells specifically. IFNβ increased the phagocytosis of apoptotic T‐cells to 36.8% above the untreated controls. The enhanced phagocytic activity was selective for apoptotic T‐cells and was not mediated by increased IL‐10 secretion. Apoptotic inflammatory cells may be efficiently and rapidly removed by microglial cells in the autoimmune‐inflamed human CNS. The in vitro increase of phagocytosis by IFNβ merits further investigations whether this mechanism could also be therapeutically exploited. © 2003 Wiley‐Liss, Inc.
Cytokine, chemokine and growth factor gene profiling of cultured human astrocytes after exposure to proinflammatory stimuli
Authors: Meeuwsen Sonja , Persoon‐Deen Carla , Bsibsi Malika , Ravid Rivka , Noort Johannes M. Van 
Published: July 2003

AbstractAstrocytes play key roles in CNS development, inflammation, and repair by producing a wide variety of cytokines, chemokines, and growth factors. Understanding the regulation of this network is important for a full understanding of astrocyte functioning. In this study, expression levels of 268 genes encoding cytokines, chemokines, growth factors, and their receptors were established in cultured human adult astrocytes using cDNA arrays. Also, changes in this gene profile were determined following stimulation with TNFα, IL‐1β, and IFNγ. The data obtained reveal a highly reproducible pattern of gene expression not only between different astrocyte cultures from a single source, but also between astrocytes from different donors. They also identify several gene products not previously described for human astrocytes, including a.o. IL‐17, CD70, CD147, and BIGH3. When stimulated with TNFα astrocytes respond with increased expression of several genes, notably including those encoding the chemokines CCL2 (MCP‐1), CCL5 (RANTES), and CXCL8 (IL‐8), growth factors including BMP‐2A, BMP‐3, neuromodulin (GAP43), BDNF, and G‐CSF, and receptors such as the CRF receptor, the calcitonin receptor (CTR), and TKT. The response to IL‐1β involves largely the same range of genes, but responses were blunted in comparison to the TNFα response. Treatment with IFNγ had no or only marginal effects on expression of any of the 268 genes analyzed. Astrocytes treated with a mixture of all three stimuli together displayed responses that are largely similar to those found in response to TNFα or IL‐1β alone, with only few additional synergistic effects. The Supplementary Material referred to in this article can be found at the GLIA website (http://www.interscience.wiley.com/jpages/0894‐1491/suppmat/2003/v43.html) © 2003 Wiley‐Liss, Inc.
Microglia density decreases with age in a mouse model of Huntington's disease
Authors: Ma Li , Morton A. Jennifer , Nicholson Louise F.B. 
Published: July 2003

AbstractHuntington's disease (HD) is characterized by selective neuronal loss and reactive gliosis. In the R6/2 transgenic HD mouse model, there is no selective cell loss, although astrocytosis has been reported. Since there have been no previous studies on microglia in this model, we have undertaken a detailed investigation of microglia in six different forebrain regions in the R6/2 mouse and their wild‐type littermates at two time points. Microglia were identified using the histochemical marker isolectin B4 and interactions of genotype, region, and age were analyzed. Results showed that there was a significant decrease in the number of microglia with age in both wild‐type and R6/2 brains, which was more pronounced in the transgenic mouse. There were also morphological changes with age observed in both genotypes. As early as 7 weeks of age, structural microglial abnormalities could be seen in R6/2 brains, including bulbous swellings and long stringy processes; comparable changes were seen at 16 weeks in wild‐type brains. At 14.5 weeks, microglia in R6/2 mouse brains were smaller in size with condensed nuclei and fragmentation of their processes. We suggest that the density and morphology of microglia change with normal aging and that this process is accelerated in R6/2 brains. Such changes in the dynamic status of microglia may lead to an impairment of their neurosupportive functions. Further studies are needed to understand better the role of microglia in aging and neurodegeneration. © 2003 Wiley‐Liss, Inc.
Binding of an antibody against a noncompact myelin protein to presumptive glial cells in the visual system of the crab Ucides cordatus
Authors: Da Silva Simone Florim , Bressan Cristine M. , Cavalcante Leny A. , Allodi Silvana 
Published: July 2003

AbstractGlial cells, in both vertebrate and invertebrate nervous systems, provide an essential environment for developmental, supportive, and physiological functions. However, information on glial cells themselves and on glial cell markers, with the exception of those of Drosophila and other insects, is not abundant in invertebrate organisms. A common ultrastructural feature of invertebrate nervous systems is that layers of glial cell cytoplasm‐rich processes ensheath axons and neuronal and glial somata. In the present study, we have examined the binding of a monoclonal antibody to 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase) in the compound eye and optic lobe of the crab Ucides cordatus using both light and electron microscopy. CNPase is a noncompact myelin protein that is a phenotypic marker of oligodendroglial and Schwann cells, is apparently involved in the ensheathment step prior to myelin compaction, and is also expressed by the potentially myelinating olfactory ensheathing glia. CNPase has raised much interest, first by virtue of its unusual enzymatic activity and more recently by its membrane‐skeletal features and possible involvement in migration or expansion of membranes. We have found CNPase‐like immunoreactivity in most cells of the compound eye basement membrane and both in optic cartridges of the synaptic layer and cells of the outer sublayer of the lamina ganglionaris. The results suggest that in the crab visual system some, but not all, glial cells, including some adaxonal glia, may express the noncompact myelin protein CNPase or a related protein. GLIA 9999:000–000, 2003. © 2003 Wiley‐Liss, Inc.
Reducing stigma and discrimination against older people with mental disorders: a technical consensus statement
Authors: Graham Nori , Lindesay James , Katona Cornelius , Bertolote José Manoel , Camus Vincent , Copeland John R. M. , de Mendonça Lima Carlos A. , Gaillard Michel , Gély Nargeot Marie Christine , Gray John , Jacobsson Lars , Kingma Mireille , Kühne Nicolas , O'Loughlin Anne , Rutz Wolfgang , Saraceno Benedetto , Taintor Zebulon , Wancata Johannes 
Published: July 2003

AbstractThis technical consensus statement is jointly produced by the Old Age Psychiatry section of the World Psychiatric Association and the World Health Organization, with the collaboration of several NGOs and the participation of experts from different Regions.It is intended to be a tool for (i) promoting debate at all levels on the stigmatisation of older people with mental disorders; (ii) outlining the nature, causes and consequences of this stigmatisation; and (iii) promoting and suggesting policies, programmes and actions to combat this stigmatisation. Copyright © 2003 John Wiley & Sons, Ltd.
Stigma and discrimination against older people with mental disorders in Europe
Authors: de Mendonça Lima Carlos A. , Levav Itzhak , Jacobsson Lars , Rutz Wolfgang 
Published: July 2003

AbstractBackground and objectivesThe European Office of the World Health Organization (WHO/EURO) has established a Task Force On Destigmatization. Upon the release of the Technical Statement on Old Age Psychiatry ‘Reducing stigma and discrimination against older people with mental disorders’, the Task Force run a small survey in two European subregions to investigate the extent of stigma and discrimination with reference to the elderly person affected from a psychiatric disorder in the countries of those subregions.MethodsWHO/EURO mental health counterparts completed a short questionnaire inquiring on the inclusion of epidemiological studies on the elderly in their country's research program; the time devoted to the teaching to old age psychiatry during psychiatric residence; the degree of coverage of services for the elderly person and their caregivers; and the extent of stigma present in society with regard to three psychiatric disorders.ResultsStigma and discrimination seem to be present both in the health sector and among the public at large.ConclusionThe development of effective health and social facilities to support older persons with mental disorders should be a high priority of any strategy to reduce stigma and discrimination. These facilities should coordinate their efforts with those of other sectors of society to reach the highest possible impact. Copyright © 2003 John Wiley & Sons, Ltd.
Teaching and training in old age psychiatry: a general survey of the World Psychiatric Association member societies
Authors: Camus Vincent , Katona Cornelius , de Mendonça Lima Carlos Augusto , Abdel Hakam Addul Moneim , Graham Nori , Baldwin Robert , Tataru Nicoletta , Chiu Edmond 
Published: July 2003

AbstractObjectiveOne of the main goals of the World Psychiatric Association (WPA) section on old age psychiatry is to promote its discipline and consequently to help member societies to promote and develop locally specific medical education programmes in old age psychiatry. In order to target its support to the needs expressed by the member societies, the section conducted a survey within the WPA during the year 2001.MethodA questionnaire was sent to each of the 116 WPA member societies in 93 countries. It assessed the level of development of medical education in old age psychiatry in each country, as well as the perceived needs in educational material.ResultsAnswers were obtained from 50 WPA member societies (response rate 54%) from 48 countries (response rate 52%). The existence of specific old age psychiatry services was reported in 40 (83%) countries, but the discipline is recognized as a subspecialty in only 13 (27%). Formal teaching in old age psychiatry was reported at the undergraduate level in 44 (92%) countries. Specific learning objectives for postgraduate training were reported in 30 (86%) of the countries where the discipline is not yet recognized as a subspecialty. Specific Continuing Medical Education (CME) programs were however reported in only 50% of the countries. Support for the development of educational material was mostly thought to be useful at the postgraduate level. Depression, dementia, psychopharmacology and psychotherapy were among the most frequently cited areas in which educational material might be usefully provided.ConclusionSupport for the development of postgraduate training is seen as the most pressing need by WPA member societies. Such support could help to increase the level of recognition of the discipline locally and hence provide more effective support to older people with mental disorders. Copyright © 2003 John Wiley & Sons, Ltd.