bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glial cell lineage in the cerebral cortex: A review and synthesis
Authors: Cameron Richard S. , Rakic Pasko 
Published: January 2005

AbstractThe present review is focused on the cell lineage relationships underlying gliogenesis in the cerebral cortex. Studies conducted both in vivo and in vitro suggest that the process of cortical gliogenesis involves a hierarchy of progressively restricted progenitor cell pools. In the cerebral cortex, as well as other areas of the central nervous system, glial cells differentiate from one another through a series of steps that can be defined at molecular, structural, and functional levels. Although the precise timing, sequence, and diversity of the steps involved in cortical gliogenesis are still not fully defined, the emerging picture suggests that both cell lineage and cell‐cell interactions play a synergetic role in the determination and maintenance of the proper blend of glial cells in the cerebrum.
The diversity and pattern of glia during axon pathway formation in the drosophila embryo
Authors: Klämbt Christian , Goodman Corey S. 
Published: January 2005

AbstractEnhancer trap lines have been used to generate a collection of molecular lineage markers specific for different subsets of glia in the Drosophila embryo. Using these markers, we have been able to describe the diversity and pattern of glia along the major axon pathways in the embraynic central and peripheral nervous system. Just as these and other studies show the great diversity of embryonic glia, so too the enhancer trap lines described here point to a remarkable degree of molecular heterogeneity, and probably a concomitant functional specificity, of the embryonic glia.
Diversity amongst the microglia in growing and regenerating fish CNS: Immunohistochemical characterization using FL. 1, an anti‐macrophage monoclonal antibody
Authors: Dowding Alan J. , Maggs Alison , Scholes John 
Published: January 2005

AbstractWe have immunohistochemically characterized the forms and distribution of microglia—the macrophages of the CNS—in fish, using a new monoclonal antibody (mAb), FL.1. This mAb specifically reacts with resident macrophages throughout the body in Oreochromine fish, including Kupffer cells, gut‐associated myeloid cells, and peritoneal macrophages, as well as with microglia, but circulating monocytes are not labelled with FL.1. The FL.1‐epitope, which is lost following treatment with reducing agents, has an extracellular location and is associated with three integral membrane glycoprotein variants.FL.1‐staining shows that microglia are extremely abundant throughout the fish CNS. For example, they comprise a third of the glia in the optic nerve, and 30% of all cells, including neurons, in the spinal cord, i.e., fish have about tenfold more microglia than mammals. Two forms of FL.1‐positive microglia are predominant in fish, one resembling their mammalian counterparts, but less ramified, and the other comprising smaller rounded cells with very little cytoplasm, which are most numerous in the ependymal region of the optic tectum.Apart from the conventional microglia, the optic nerves also contain large lipid‐laden macrophages which comprise a third form of FL.1‐positive cell in the CNS. Fish optic nerves contain astrocytes of a distinct type which form reticular networks, but lack connections to capillaries (Maggs and Scholes, J. Neurosci. 1990;10:1600–1614). The co‐distribution of foamy macrophages may have a metabolic role that is performed by ordinary astrocytes elsewhere in the CNS. An antiserum against the β2 subunit of the human leukocyte integrins (Kishimoto et al., Cell 1987a; 50:193–202) was found selectively to recognize the foamy macrophages in Oreochromis.Following lesion to the optic nerve, FL.1‐labelling shows that microglia proliferate throughout the visual pathway. In the optic tectum, the additional FL.1‐positive cells are concentrated in the vicinity of degenerating retinal axons and their terminals. Most of the microglia in the injured optic nerve have amoeboid morphologies, and the foamy macrophages become depleted.
Further studies of electrogenic Na+/HCO cotransport in glial cells of necturus optic nerve: Regulation of pHi
Authors: Astion M. L. , Chvatal A. , Orkand R. K. 
Published: January 2005

AbstractIn the presence of Ba++, an increase in the bath HCO at constant CO2 (i.e., Variable bath pH) produced a hyperpolarization. The hyperpolarizing effect of adding HCO3−/CO2 at constant bath pH was not significantly affected by the presence of 50 μmol/l strophanthidin. In the absence of Ba++, addition of HCO3−/CO2 at constant bath pH produced a Na+‐dependent hyperpolarization. Therefore, CO2 movements, electrogenic Na+/K+ pump activity and changes in Ba++ binding do not contribute significantly to the hyperpolarization induced by HCO3−. These results along with the results of previous studies (Astion et al: J Gen Physiol 93:731, 1989) strongly suggest that the hyperpolarization induced by the addition of HCO3− is due to an electrogenic Na+/HCO3− cotransporter, which transports Na+, HCO3− (or its equivalent), and net negative charge across the glial membrane.To study the role of electrogenic Na+/HCO cotransport in the regulation of pHi in glial cells, we used intracellular double‐barreled, pH‐sensitive microelectrodes. At a bath pH of 7.5, the mean initial intracellular pH (pHi) was 7.32 (SD 0.03, n = 6) in HEPES‐buffered Ringer's solution and 7.39 (SD 0.1, n = 6) in HCO3−/CO2 buffered solution. These values for pHi are more than 1.2 pH units alkaline to the pHi predicted from a passive distribution of protons; thus, these cells actively regulated pHi. Superfusion and with‐drawal of 15 mmol/l NH4+ induced an acidification of 0.2 to 0.3 pH units, which recovered toward the original steady‐steady‐state pHi. Recovery from acidification was stimulated by adding HCO3−/CO2 at constant pH. In HCO3−/CO2‐buffered solutions, the recovery was Na+‐dependent, inhibited by 4‐acetamido‐4′‐isothiocyanato‐stilbene‐2,2′‐disulfonic acid (SITS), and associated with a hyperpolarization of the membrane. Thus it appears that the electrogenic Na+/HCO3− cotransporter helps maintain the relatively alkaline pHi of glial cells and also contributes to the ability of glial cells to buffer changes in pH in the neuronal microenvironment.
A study of in vitro and in vivo morphological changes of ependymal cells induced by galactocerebrosides
Authors: Laabich Aicha , Graff Marie‐Noëlle , Dunel‐Erb Suzanne , Sensenbrenner Monique , Delaunoy Jean‐Pierre 
Published: January 2005

AbstractEpendymal cells in culture and in vivo were treated with mixture of galactocerebrosides. Galactocerebroside is the major glycolipid of myelin and in demyelinating diseases is found in cerebrospinal fluid. Morphological changes induced by this treatment were examined by microscopy at both optical and ultrastructural levels. In vitro, cilia, microvilli, and junctions between the cells disappeared, processes containing intermediate filaments developed, and the cells lost characteristics typical of ependymal cells and became more astrocyte‐like. As shown by vital staining with a fluorescent compound and by nuclear incorporation of bromodeoxyuridine, cells did not proliferate during the period of galactocerebroside treatment and the morphological transformation was restricted to the ependymal cells. In contrast, asialoganglioside‐GM1 and sulfatides had no effect on ependymal cell morphology. Some of the in vitro observations could be reproduced in vivo. Junctions between ependymal cells disappeared and intercellular spaces appeared between these cells and the cerebral parenchyma at the basolateral side of the ependymal layer. At the apical side, morphological modifications of junctions and cilia were less evident. As these experimental conditions resemble those existing during demyelination the morphological changes described may account for perturbations of the physiological functions of the ependymal cell.
Production and disposition of 1‐methyl‐4‐phenylpyridinium in primary cultures of mouse astrocytes
Authors: Di Monte Donato A. , Wu Ellen Y. , Irwin Ian , Delanney Louis E. , Langston J. William 
Published: January 2005

AbstractDopaminergic neurons are a primary target for 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) neurotoxicity. However, the conversion of MPTP to its neurotoxic 1‐methyl‐4‐phenylpyridinium metabolite (MPP+) is likely to occur in astrocytes via the monoamine oxidase (MAO)‐dependent formation of the 1‐methyl‐4‐phenyl‐2,3‐dihydropyridinium intermediate (MPDP+). The main purpose of this study was to characterize the molecular mechanism(s) by which MPP+, once generated by astrocytes, may reach the extracellular space to become available for the active accumulation into dopaminergic neurons. Primary cultures of mouse astrocytes were used as an in vitro model system. After the addition of MPTP, levels of MPP+ were found to increase at constant rates both intracellularly at time points when no sign of cytotoxicity was evident. In contrast, MPDP+ levels remained quite stable during 4 days of incubation in the presence of MPTP. Finally, when astrocytes were allowed to accumulate MPP+ by pretreatment with either MPTP or MPP+ and then were incubated in fresh medium not containing MPTP or MPP+, intracellular levels of MPP+ rapidly declined and corresponding amounts of this compound were found in the incubation medium. Results of this study are compatible with the following conclusions: (1) the MPP+ accumulated in the extracellular compartment during incubations with MPTP is not released from astrocytes as a consequence of its own cytotoxic effects; (2) MPP+ can be formed extracellularly presumably via autoxidation of MPDP+ after this latter compound has been generated within astrocytes and has crossed astrocyte membranes; and (3) despite its charged chemical structure, MPP+ can cross the plasma membrane toward the extracellular space after being formed within astrocytes.
Isomorphic activation of astrocytes in the somatosensory thalamus
Authors: Wells Joseph , Vietje Brad P. , Wells David G. , Paradee Janelle 
Published: January 2005

AbstractStructural recovery in the rat somatosensory thalamus after the loss of one of its major inputs provided a model for studying the changes in astrocytes associated with reactive synaptogenesis. The temporal separation of the initiation of Wallerian degeneration and reactive synaptogenesis permitted astrocytic changes to be correlated either with the removal of degeneration, early in the recovery sequence, or with synaptogenesis, later in recovery. Over a period of post‐lesion times ranging from 3 days to 13.5 months, GFAP‐positive astrocytic fibers were quantified and the population density of S‐100‐positive astrocytic cell bodies was determined in the ventral posterolateral nucleus (VPL). The relative area of astrocytic cell bodies was measured at an early peak of the increased GFAP immunoreactivity (4–5 days post‐lesion). The normal side of VPL (c‐VPL) was compared to the deafferented side of VPL (d‐VPL) and the ratio d‐VPL/c‐VPL was determined. Astrocytes in d‐VPL underwent a minimal isomorphic activation with little or no hypertrophy or proliferation but with a large increase in GFAP immunoreactivity. Prior to the initiation of synaptogenesis, there was a decrease both in GFAP immunoreactivity and in the population density of VPL astrocytes. The decreases in the recovery curves suggested that a suppression of the influence of astrocytes may have been important for sprouting and/or synaptogenesis. In other systems, where synaptogenesis was initiated early in the recovery sequence, the suppression of astrocytes that was related to synaptogenesis may have been masked by astrocytic changes related to the removal of degeneration.
Co‐cultures of microglia and astrocytes from kainic acid‐lesioned adult rat hippocampus: Effects of glutamate
Authors: Bowman Charles L. , Swann John W. , Severin Charles M. , Romanowski Marcus R. 
Published: January 2005

AbstractThe long‐standing question concerning the direct actions of glutamate on the membrane potential of astroglial cells in the central nervous system was addressed using the in vitro kainic acid‐lesioned hippocampal slice preparation and primary cell co‐cultures of astrocytes and microglia derived from such lesions. The ultrastructure of the lesioned hippocampus was examined to aid in the identification of the cells appearing in culture.In culture, microglia appeared as flat cells, less than 1 μm in thickness at the edge of the cell, but thicker (about 5 μm) near the nucleus. The cytoplasm was packed with granular inclusions. Microglia appeared in two morphological forms, amoeboid and ramified. The amoeboid form was characterized by a cell body with a single process, and was always observed 1 day after starting the cell culture. Such cells became less frequent after 1 week in culture. The ramified form appeared as a rounded cell, devoid of processes, and were frequently observed in older cultures (> 1 week). Microglia did not round up after exposure to dibutyrylcyclic adenosine monophosphate (cAMP), and did not stain for glial fibrillary acidic protein (GFAP). An ultrastructural examination of the lesion demonstrated that microglia were present and that they contained many cytoplasmic granules similar to lipofuscin‐containing granules. No filaments were observed in the cytoplasm of microglia. By contrast, the cytoplasm of astrocytes in culture had far fewer granules, rounded up to dibutyryl‐cAMP, exhibited multiple processes, and stained for GFAP. In slices, astrocytes had no lipofuscin‐containing granules, but numerous cytoplasmic filaments were present.The membrane potential of the rounded‐up cells in culture varied between −10 mV and −95 mV (while electrically unresponsive cells in the lesion varied between −47 and −95 mV). In culture, glutamate evoked a depolarization or a hyperpolarization of the membrane potential of 87% of the rounded‐up cells tested. Ionophoretic application of glutamate depolarized the membrane potential of 50% of the cells tested in the lesion.The results show that co‐cultures of microglia and astrocytes can be obtained routinely from lesions within the adult central nervous system, and that glutamate can affect the membrane potential of astrocytes in cultures derived from such adult tissue. These findings suggest that responses to glutamate, recorded from unresponsive cells (presumptive astrocytes) in the lesioned slice preparation, are likely the result of direct action of this neurotransmitter on these cells. © 1992 Wiley‐Liss, Inc.
Heterogeneity in gap junction expression in astrocytes cultured from different brain regions
Authors: Batter David K. , Corpina Richard A. , Roy Christine , Spray David C. , Hertzberg Elliot L. , Kessler John A. 
Published: January 2005

AbstractHeterogeneity among astrocytes suggests that their role in the central nervous system is more complex than is commonly recognized. This paper describes just such a functional difference, comparing gap junctions in astrocytes derived from two brain regions. Astrocytes, both in situ and in culture, employ gap junctions as a means of intercellular communication. Recent evidence utilizing cultured rat cortical and striatal astrocytes has shown that these channels consist of subunits of connexin 43, the same protein as that composing cardiac gap junctions. Here we report that astrocytes cultured from neonatal rat hypothalamus contain a greater number of functional channels than astrocytes from the striatum, a difference reflected in both connexin 43 protein and mRNA. Specifically, in hypothalamic astrocytes the level of connexin 43 protein was approximately four times that found in comparable cultures from the striatum, as determined by immunoblotting. Complementary results from immunocytochemical experiments using an antibody specific for connexin 43 reveal significantly greater fluorescence in astrocytes cultured from the hypothalamus as compared to those from the striatum. Northern blot analysis showed that connexin 43 mRNA levels were also approximately 4‐fold greater in the hypothalamic cultures, consistent with difference seen by immunoblotting. Finally, dye coupling studies using confluent cultures consistently showed that within 1 min Lucifer Yellow injected into striatal astrocytes spread to immediately surrounding cells while in hypothalamic astrocytes dye often spread to apparent third or fourth order neighbors within the same time period. Thus, the higher level of connexin 43 expression seen in hypothalamic astrocytes results in cells with greater numbers of functional channels. Interestingly, both the immunocytochemical and dye coupling experiments also revealed heterogeneity, among cells derived from each brain area, indicating that both region contain subpopulations of astrocytes. Taken together, our data show differences in gap junction expression, both within and between astrocytes derived from two brain regions. Further, this heterogeneity appears to derive from differences in either transcriptional regulation or in mRNA stability, and not from changes in the relative levels of phosphorylated forms of connexin 43. Thus, these data, which are consistent with light microscopic immunocytochemical studies in tissue sections of rat brain, predict that, in vivo, region‐specific coupling subserves functional specialization within the central nervous system. © 1992 Wiley‐Liss, Inc.
Purification and characterization of an astrocyte GABA‐carrier inducing protein (GABA‐CIP) released from cerebellar granule cells in culture
Authors: Nissen Jan , Schousboe Arne , Halkier Torben , Schousboe Inger 
Published: January 2005

AbstractA glycoprotein that induces γ‐aminobutyric acid (GABA) carriers in cultured cerebellar astrocytes was isolated and purified from conditioned media from cultured cerebellar granule cells by anion exchange chromatography, affinity chromatography, and gel filtration. Following gel filtration three fractions corresponding to Mr 30,000, 60,000, and 240,000 exhibited GABA carrier inducing activity. SDS‐PAGE of the Mr 30,000 fraction revealed under non‐reducing conditions three bands corresponding to Mr 30,000, 60,000, and 120,000. Under reducing conditions only the band corresponding to an Mr of 30,000 was visible. An identical N‐terminal amino acid sequence and amino acid composition was found in the Mr 30,000 and the Mr 60,000 fraction from the gel filtration. These results suggest that the protein polymerizes into di‐ and tetramers. Computer base analysis of the N‐terminal amino acid sequence revealed no obvious homology with previously reported N‐terminal amino acid sequences.Application of the glycoprotein to cerebellar astrocytes led time and dose dependently to an increased GABA uptake. The effect became maximal after 24h exposure of the cells. Kinetic analysis of the GABA uptake showed that exposure of the astrocytes to the glycoprotein led to an increase in Vmax for GABA uptake without affecting Km, suggesting an increase in the number of GABA carrier molecules. Addition of actinomycin D together with the glycoprotein abolished this effect suggesting that the glycoprotein acts by stimulating de novo synthesis of GABA carriers. Hence, the newly purified protein secreted from neurons is named GABA‐carrier inducing protein (GABA‐CIP). © 1992 Wiley‐Liss, Inc.
Microglial involvement in experimental autoimmune inflammation of the central and peripheral nervous system
Authors: Gehrmann Jochen , Gold Ralf , Linington Christopher , Lannes‐Vieira Joseli , Wekerle Hartmut , Kreutzberg Georg W. 
Published: January 2005

AbstractMicroglial cells form a network of potential antigen presenting cells throughout the nervous system. Much progress has recently been made towards a better understanding of their immunological properties. This study examines their activation in 2 models of T cell‐mediated autoimmune inflammation of the nervous system, experimental autoimmune encephalomyelitis (EAE) and its peripheral counterpart, experimental autoimmune neuritis (EAN), induced by the transfer of antigen‐specific T cell lines. In both models microglial activation occurs at early stages of the disease. Activated microglial cells show an increased expression of MHC class I and II antigens. In EAE ultrastructural analysis revealed that MHC antigen expression is pronounced on perivascular microglial cells, suggesting this cell population may be important for antigen presentation at a site close to the blood‐brain barrier. In contrast to EAE, the microglial reaction in EAN occurs at sites remote from the inflammatory response in the peripheral nerve, not only in the spinal cord but also in the terminal projection fields of primary sensory neurons in the lower brainstem. This early microglial activation in EAN suggests that a rapid and remote signaling mechanism can operate following peripheral inflammation. Immuno‐electron microscopy revealed that activated microglial cells are also involved in the synaptic deafferentation of spinal cord motoneurons during autoimmune reactions. The rapid involvement of microglial cells in experimental autoimmune inflammation of the nervous system further points to their role as the main intrinsic immuneffector cell population of the central nervous system.
Cytotoxicity of microglia
Authors: Banati Richard B. , Gehrmann Jochen , Schubert Peter , Kreutzberg Georg W. 
Published: January 2005

AbstractThe most characteristic property of microglia is their swift activation in response to neuronal stress and their capacity for site‐directed phagocytosis. The transformation of microglia into intrinsic brain macrophages appears to be under strict control and takes place if neuronal and/or terminal degeneration occurs in response to nerve lesion. The differentiation of microglia into brain macrophages is accompanied by the release of several secretory products, e.g., proteinases, cytokines, reactive oxygen intermediates, and reactive nitrogen intermediates. Interference with the microglial activation or the productions of cytotoxic metabolites by microglia may thus offer new therapeutic opportunities for the prevention of neuronal cell death in CNS disease.
Pregnenolone metabolism in rodent embryonic neurons and astrocytes
Authors: Kabbadj Khadija , El‐Etr Martine , Baulieu Etienne‐Emile , Robel Paul 
Published: January 2005

AbstractThe rat CNS has been previously shown to synthesize pregnenolone (PREG) and to convert it into progesterone (PROG) and some of its 5α‐reduced metabolites. However, the brain cell types involved in the metabolic conversions of PREG are poorly known. Selective conditions were used to obtain purified cultures of neurons and astrocytes from mouse or rat fetal striatum and cerebral cortex. Neurons converted PREG to only one identified metabolite, 20α‐dihydro PREG, whereas astrocytes converted PREG also to PROG, 5α‐dihydro PROG, and 3α (3β)‐5α‐tetrahydro PROG. Therefore, astrocytes can convert the neurosteroid PREG into the steroid hormone PROG and the neuromodulatory steroid 3α, 5α‐tetrahydro PROG, whereas neurons lack the Δ5‐3β‐hydroxysteroid dehydrogenase isomerase activity (and cholesterol side‐chain cleavage activity), necessary for the biosynthesis of PROG. Provision of steroid substrates is another example of cross‐talk between glial cells and neurons.