bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of the neurofibromatosis type 1 gene product, neurofibromin, during Schwann cell differentiation
Authors: Gutmann D. H. , Tennekoon G. I. , Cole J. L. , Collins F. S. , Rutkowski J. L. 
Published: January 2005

AbstractNeurofibromin, the product of the neurofibromatosis type 1 (NF1) gene, is a ∼250 kDa protein expressed predominantly in cortical neurons and oligodendrocytes in the central nervous system (CNS) and sensory neurons and Schwann cells in the peripheral nervous system (PNS). To gain insight into the biological role of neurofibromin in Schwann cells, the modulation of NF1 gene expression in a Schwann cell line (MT4H1) stimulated to either proliferate or differentiate in response to agents that elevate intracellular cAMP was examined. Untreated cells and cells exposed to mitogenic doses of forskolin (1–10 μM) or 8‐bromo‐cAMP (0.1 mM) expressed low levels of NF1 MRNA and the protein was barely detectable. High doses of forskolin (100 μM) or 8‐bromo‐cAMP (1 mM) induced the expression of both myelin P0 protein and neurofibromin with an identical time course. Although NF1 mRNA levels peaked within 1–6 hr, the rise in neurofibromin was not apparent until 24–48 hr and peaked 72 hr after treatment. P0 and neurofibromin were also coinduced by cell‐cell contact in high density, untreated cultures. Moreover, differentiation initiated by either cAMP stimulation or high density culture conditions was associated with predominant expression of the type 2 NF1 mRNA isoform. In contrast, type 1 NF1 mRNA isoform expression was observed in untreated Schwann cells or those stimulated with mitogenic doses of forskolin or 8‐bromo‐cAMP. A switch from the type 1 neurofibromin that can efficiently down‐regulate p21‐ras to the type 2 isoform with reduced activity may facilitate a p21‐ras signaling pathway associated with Schwann cell difrerentiation. © 1993 Wiley‐Liss, Inc.
Culture model for the study of cerebral malaria: Antibodies from Plasmodium falciparum‐infected comatose patients inhibit the dendritic development of Purkinje cells
Authors: Calvet M.‐C. , Druilhe P. , Camacho‐Garcia R. , Calvet J. 
Published: January 2005

AbstractThe in vitro development of kitten Purkinje cells was inhibited by sera or IgG from cerebral malaria (CM) patients but not by sera from acute non‐complicated malaria (NCM) cases. This inhibitory effect, quantified by computer‐assisted methods, concerned the dendritic (though not the axonal) development and was found to be related to the presence in CM sera of self‐reactive antibodies of the IgG class. These results suggest that protection acquired against the major complication of Plasmodium falciparum malaria may correspond to the repression of an abnormal stimulation of autoreactive B cells. © 1993 Wiley‐Liss, Inc.
Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein
Authors: Gijbels K. , Proost P. , Masure S. , Carton H. , Billiau A. , Opdenakker G. 
Published: January 2005

AbstractGelatinases in inflammatory demyelinating diseases of the central nervous system (CNS) were studied using actively induced experimental autoimmune encephalomyelitis (EAE) in mice as a model system. Clinical disease scores correlated in time and in intensity with pathology parameters such as cytosis in the cerebrospinal fluid (CSF), inflammatory infiltrates, and demyelination in the CNS. Zymographic analysis was employed to measure gelatinases A and B in the CSF from individual animals. According to their apparent molecular weight (MW), gelatinases A and B appeared with a MW of 65 and 95 kDa, respectively. The 65 kDa form was present in all samples, even in those derived from non‐induced animals, whereas the 95 kDa form was present only in samples from animals developing EAE. The levels of 95 and 65 kDa gelatinase correlated with the CSF cytosis. In vitro digestion of myelin basic protein (MBP) with gelatinase B and analysis of the cleavage products by protein sequence analysis pinpointed two cleavage sites in conserved regions of MBP. Gelatinase production within the CNS may constitute an important pathogenic mechanism for both the disruption of the blood‐brain barrier and the destruction of myelin, as observed in several neuroinflammatory disorders. © 1993 Wiley‐Liss, Inc.
Glycerophosphorylcholine phosphocholine phosphodiesterase activity during the differentiation of glial progenitor cells
Authors: Monge M. , Yuan J. , Cabon F. , Zalc B. , Kanfer J. N. 
Published: January 2005

AbstractO‐2A progenitor cells were grown in medium containing either 1% or 10% fetal calf serum (FCS) for 4 weeks. The cells in 1% FCS were 75% oligodendrocytes by 3 weeks in culture. The cell population was so overgrown with astrocytes in the 10% medium that an accurate estimate of cell number could not be made. The activities of glycerophosphorylcholine phosphocholine phosphodiesterase (GPC‐PC‐PdE), p‐nitrophenylphosphorylcholine phosphodiesterase (pNPPC‐PC‐PdE), and ceramide UDP galactose galactosyl transferase (CGalT) were barely detectable in the cells grown in 10% FCS. The activities of these 3 enzymes were low in the cells grown in 1% FCS for the first 2 weeks and then all 3 increased manyfold. These observations reinforce the evidence previously accrued showing that these two phosphodiesterase activities (GPC‐PC‐PdE and pNPPC‐PC‐PdE) are markers of oligodendroglial cells as well as myelin. In contrast, glycerophosphorylcholine choline phosphodiesterase (GPC‐C‐PdE) activities were present in cells grown in both 1% and 10% FCS. © 1993 Wiley‐Liss, Inc.
Lipocortin 1 immunoreactivity identifies microglia in adult rat brain
Authors: McKanna J. A. 
Published: January 2005

AbstractImmunohistochemical localization of two Ca++‐binding proteins, Lipocortin 1 (LC1) and S100‐β, demonstrates two distinct classes of primitive glia in the floor plate of rat embryos. With proper fixation (formalin‐lysine‐periodate‐acetic acid), dendritic glia in the CNS of adult rats also apparently stain for either LC1 or S100‐β in the ratio of 1:3. In order to further distinguish and identify these two glial classes, we have examined their population density, topography, and responses to localized neuron death. Neurons of the ipsilateral thalamus undergo apoptosis following cortical ablation; the contralateral thalamus serves as control. By eight days post‐lesion, the number of LC1 cells in the ipsilateral thalamus has increased >4‐fold, the increase comprising primarily activated phagocytes adjacent to degenerating neurons. The S100‐β glia in the same region are virtual‐ ly indistinguishable from control; but background staining (apparently representing extracellular S100‐β) is increased. Thus, the responses of dendritic LC1 glia resemble those previously described for microglia and are quite different from the astrocytes identified by S100‐β immunoreactivity. Both dendritic and activated forms of LC1 glia stain with the microglial marker, Griffonia simplicifolia iso‐lectin B4. However, before the correspondence of LC1 glia and microglia can be confirmed, two anomalies require resolution: (1) the LC1 glia are greater in number and more evenly distributed than microglia marked with other methods; (2) the dendritic LC1 glia apparently are progeny of primitive glia that form the midline raphe of the embryonic floor plate. The participation of LC1 glia in the removal of CNS debris supports the hypothesis that LC1 plays anti‐inflammatory and/or immunosuppressive roles in phagocytes. © 1993 Wiley‐Liss, Inc.
Orthograde transport and release of insulin‐like growth factor I from the inferior olive to the cerebellum
Authors: Nieto‐Bona M. P. , Garcia‐Segura L. M. , Torres‐Aleman I. 
Published: January 2005

AbstractInsulin‐like growth factor I (IGF‐I) and its receptor are expressed in functionally related areas of the rat brain such as the inferior olive and the cerebellar cortex. A marked decrease of IGF‐I levels in cerebellum is found when inferior olive neurons are lesioned. In addition, Purkinje cells in the cerebellar cortex depend on this growth factor to survive and differentiate in vitro. Thus, we consider it possible that IGF‐I forms part of a putative trophic circuitry encompassing the inferior olive and the cerebellar cortex and possibly other functionally connected areas. To test this hypothesis we have studied whether IGF‐I may be taken up, transported, and released from the inferior olive to the cerebellum. We have found that 125I‐IGF‐I is taken up by inferior olive neurons in a receptor‐mediated process and orthogradely transported to the cerebellum. Thus, radioactivity found in the cerebellar lobe contralateral to the injection site in the inferior olive was immunoprecipitated by an anti‐IGF‐I antibody, co‐eluted with 125I‐IGF‐I in an HPLC column, and co‐migrated with 125I‐IGF‐I in an SDS‐urea polyacrylamide gel electrophoresis. Time‐course studies indicated that orthograde axonal transport is relatively rapid since 30 min after the injection, radiolabeled IGF‐I was already detected in the contralateral cerebellum. Furthermore, transport of IGF‐i from the inferior olive is specific since when 125I‐neurotensin was injected in the inferior olive or when 125I‐IGF‐I was injected in the pontine nucleus, no radiactivity was found in the contralateral cerebellum. In addition, no specific transport of 125I‐IGF‐I was found in climbing fiber‐deafferented rats or when excess unlabeled IGF‐I was co‐injected with 125I‐IGF‐I. We next studied whether IGF‐I is released by inferior olive neurons. We found that the release of IGF‐I from cerebellar slices of normal rats was significantly greater in response to depolarizing stimuli than that from slices obtained of climbing fiber‐deafferented animals. Indeed, in vitro release of IGF‐I in response to KCI or veratridine was almost completely abolished in the latter. These data suggest that IGF‐I is taken up by inferior olive neurons through IGF‐I receptors and transported to the cerebellum through their axons without any major modification. Moreover, the release of IGF‐I from the cerebellum after depolarization depends on the presence of climbing fiber afferents. Altogether these results indicate that the olivo‐cerebellar pathway is able to take up, orthogradely transport, and release IGF‐I. Since a similar process has been described in the visual system for basic fibroblast growth factor (bFGF), we propose that IGF‐I, bFGF, and possibly other growth factors may constitute afferent trophic signals involved in plastic mechanisms within specific neural circuitries. © 1993 Wiley‐Liss, Inc.
Immediate early gene activation during the initial phases of the excitotoxic cascade
Authors: Walker P. D. , Carlock L. R. 
Published: January 2005

AbstractDirect brain injections of the N‐methyl‐D‐aspartate receptor agonist quinolinic acid (QA) trigger an excitotoxic cascade characterized by rapid neuronal death and glial/immune cell activation. The present study compared the timing of immediate early gene (IEG; c‐fos, c‐jun, jun‐B, and zif/268) induction with the response of neuronal ranscripts during the first 24 hr of a QA lesion within the rodent striatum. Following QA exposure, IEG mRNA induction periods extended from 30 min to 24 hr. Several characteristics of this prolonged transcriptional response suggest that separate cell populations (neuronal vs. glial) originate individual IEG phases during the first day of the lesion. The first IEG phase was rapid and peaked at 60 min. This initial IEG phase, likely neuronal in origin, was dominated by robust increases in the expression of c‐fos, jun‐B, and zif/268 mRNAs in contrast to small increases in c‐jun expression. A second, delayed IEG phase was initiated after the first hour and extended to 24 hr. This IEG phase was more intense and continued beyond the period of neuronal survival as detected by the loss of neurotransmitter‐specific mRNAs (preprotachykinin, preproenkephalin, and glutamic acid decarboxylase). During this phase, c‐jun mRNA levels coordinately increased with c‐fos. Interestingly, the transcriptional peak of the delayed IEG phase occurred between 4 and 12 hr, the time which corresponded to the rapid decline of neuronal transcripts. The temporal association of a delayed phase of IEG induction, possibly originating in nonneuronal cells, with neuronal death during the acute phases of the excitotoxic cascade suggest a link between glial IEG activation and the spreading cascade of neuronal damage characteristic of excitatory amino acid receptor overstimulation. © 1993 Wiley‐Liss, Inc.
Movement of embryonic chick sympathetic neurons on laminin in vitro is preceded by neurite extension
Authors: Liang S. , Crutcher K. A. 
Published: January 2005

AbstractChick sympathetic neurons (E‐9) are capable of moving on a laminin substrate but not on more adhesive substrates in vitro. The effect of laminin is dose‐dependent and reduced by the addition of anti‐laminin antibodies, whereas soluble laminin does not stimulate movement. The onset of neuronal movement is preceded by, and highly correlated with, the onset of neurite formation. The addition of 1,2 dioctanoyl‐snglycerol (DAG), a stimulator or protein kinase C that has been shown to inhibit neurite outgrowth, was found to delay both process formation and neuronal movement but did not affect the correlation between these two measures. These results support the conclusion that laminin stimulates primary neuronal movement in vitro and suggest that the mechanism underlying movement involves process formation followed by “towing” of the cell body by the advancing process. The similarities of this in vitro behavior to that observed in vivo suggest that similar mechanisms may underlie neuronal movement in the developing nervous system as suggested by Morest (Z Anat Entwicklungsgesch 130:265–305, 1970) and Liesi (EMBO J 4:1163–1170, 1985; Exp Neurol 117:103–113, 1992). © 1993 Wiley‐Liss, Inc.
High resolution labeling of cholinergic nerve terminals using a specific fully active biotinylated botulinum neurotoxin type A
Authors: Arribas M. , Blasi J. , Egea G. , Fariñas I. , Solsona C. , Marsal J. 
Published: January 2005

AbstractWe report here on the synthesis and characterization of a fully active biotinylated derivative of the botulinum neurotoxin type A. Different ratios of biotin:botulinum toxin were tested to optimize derivatizing conditions and a ratio of 35:1 was selected for further experiments. The average number of biotin groups per toxin molecule was estimated to be 7.8, occurring at both heavy and light chains, and almost all externally located and easily accessible to recognition by streptavidin. The modified toxin retained its toxicity and its ability to interact with biological membranes. Apart from its suitability for detection in Western blots and in microtiter well plates, biotinylated botulinum toxin proved to be adequate for morphological labeling studies at both light and electron microscopy. Peroxidase histochemistry in cryostat sections of intoxicated rat hemidiaphragm muscles showed a distinct labeling of end‐plates. Electron microscopy studies were performed on the electric organ of Torpedo marmorata using colloidal gold‐conjugated streptavidin for detection. After intoxication of electric organ fragments with the modified toxin, gold labels were found associated with the presynaptic plasma membrane of nerve terminals and with the membrane of synaptic vesicles. Moreover, the distribution of biotinylated botulinum toxin binding sites over the membrane of synaptosomes isolated from the electric organ of Torpedo and their relationship with intramembrane particles were analyzed using the replica‐staining label‐fracture technique. It was found that the toxin is never associated with intramembrane particles. © 1993 Wiley‐Liss, Inc.
Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic injury to the central nervous system
Authors: Giulian D. , Corpuz M. , Chapman S. , Mansouri M. , Robertson C. 
Published: January 2005

AbstractReactive microglia and invading macrophages, Which appear in brain damaged by stroke or trauma, secrete neuron‐killing factors. This release of cytotoxic substances is a delayed process and is not detected until inflammatory cells reach a peak of reactivity by the second day after injury. Proximity to the site of injury and density of mononuclear phagocytes determine in part the amount of neurotoxic activity released by injured tissues. Moreover, drugs that suppress the accumulation of reactive microglia and macrophages also reduce tissue production of neuron poisons. Neurotoxins released by brain inflammatory cells or extracted directly from inflamed tissues are heat‐stable, protease‐resistant molecules <500 daltons with actions blocked by N‐methyl‐D‐aspartate (NMDA) receptor antagonists. These molecules are distinguished from free radical intermediates, bind to cation exchange resins, lack carboxyl moieties, and are separated from excitatory amino acids including glutamate or aspartate and from the NMDA receptor‐mediated toxin quinolinc acid by ion exchange and reverse phase chromatography. Our data suggest that an unrecognized class of neuron‐killing molecules produced by inflammatory cells mediate the delayed neuronal loss associated with stroke and trauma. © 1993 Wiley‐Liss, Inc.
CNS white matter can be altered to support neuronal outgrowth
Authors: Carpenter M. K. , Hassinge T. D. , Whalen L. R. , Kater S. B. 
Published: January 2005

AbstractPrevious work has demonstrated that white matter in the adult mammalian CNS inhibits cell adhesion and neurite outgrowth. This phenomenon has been investigated most recently by culturing neurons on cryostat sections of the adult CNS. Employing this same technique, we have found, in accord with others, that neurons seldom adhere to or grow on central nervous system white matter but will attach and grow on gray matter. In the experiments presented here, embryonic rat hippocampal neurons were grown on cryostat sections from the adult rat CNS, in the presence of brain derived glial cocultures. It was found that the white matter in cryostat sections can be modified by interaction with medium conditioned by brain‐derived glial cells. Neurons plated on sections pretreated by such media show significant increases in both attachment and neurite outgrowth. The activity contained in glial conditioned medium is likely complex in nature. While the majority of the activity can be eliminated by heat treatment and trypsinization, neural adhesion but not neurite initiation is affected by protease treatment. Therefore, cell attachment and neurite outgrowth may be regulated by different factors in the conditioned media. © 1994 Wiley‐Liss, Inc.
Lymphoid tissues induce NGF‐dependent and NGF‐independent neurite outgrowth from rat superior cervical ganglia explants in culture
Authors: Kannan Y. , Stead R. H. , Goldsmith C. H. , Bienenstock J. 
Published: January 2005

AbstractInduction of neurite outgrowth from superior cervical ganglia (SCG) by rat lymphoid tissues was studied using a tissue culture model. Neonatal rat SCG were cultured with 6–12‐week‐old rat thymus, spleen, or mesenteric lymph node (MLN) explants in a Martrigel layer, in defined culture medium without exogenous nerve growth factor (NGF). SCG were also co‐cultured with neonatal rat heart (as positive control) or spinal cord (SC; as negative control). To determine whether inflammation affects the ability of lymphoid tissues to induce neurite outgrowth, we also examined MLN at various times after infecting rats with Nippostrongylus brasiliensis (Nb‐MLN). In one series of experiments, a single lymphoid tissue explant was surrounded by four SCG at a distance of 1 mm. The extent of neurite outgrowth was determinded by counting the number of neurites 0.5 mm away from each ganglion at several time points. Adult thymus and, to a lesser extent, spleen had strong stimulatory effects on neurite outgrowth from SCG after 12 hr or more in culture. For thymus tissue, this was similar to the positive control heart explants. MLN from normal rats had minimal effect on neurite outgrowth; however, Nb‐MLN showed a time‐dependent enhancement of the neurite outgrowth, maximal at 3 weeks after infection. The relative efficacy of neurite outgrowth induction (heart ≥ thymus ≥ Nb‐MLN ≥ spleen ≥ MLN ≥ SC) was confirmed in a second series of experiments where one SCG was surrounded by three different tissue explants. We then examined the role of 2.5S NGF, a well‐known trophic factor for sympathetic nerves, in the lymphoid tissue‐induced neurite outgrowth. Anti‐NGF treatment of co‐cultures of SCG and heart almost completely blocked the neurite outgrowth. Anti‐NGF also significantly inhibited thymus‐ and spleen‐induced neurite outgrowth, but not as effectively as heart‐induced neuritogenesis (93,80, and 77% inhibition at 24 hr; 86,70, and 68% inhibition at 48 hr for heart, thymus, and spleen, respectively). On the other hand, anti‐NGF inhibited only 8% of neurite outgrowth induced by 3‐week post‐infection Nb‐MLN at 24 hr, and 41% at 48 hr. These data show that several adult rat lymphoid tissues exert neurotrophic/tropic effects. The predominant growth factor in thymus and spleen is NGF, while Nb‐MLN produces factor(s) which is (are) immunologically distinguishable from NGF. These neurotrophic/tropic factors are produced during the reactive lymphoid hyperplasia that forms part of the inflammatory response against the nematode, N. brasiliensis. This suggests the possibility that cytokines produced by lymphocytes or other inflammatory cells may stimulate sympathetic neurite outgrowth in vivo. © 1994 Wiley‐Liss, Inc.
Role for the stem cell factor/KIT complex in schwann cell neoplasia and mast cell proliferation associated with neurofibromatosis
Authors: Ryan J. J. , Klein K. A. , Neuberger T. J. , Leftwich J. A. , Westin E. H. , Kauma S. , Fletcher J. A. , DeVries G. H. , Huff T. F. 
Published: January 2005

AbstractSchwann cells are the primary cell type in the disfiguring lesions associated with neurofibromatosis type 1 (NF‐1). These lesions also contain abnormally high numbers of mast cells, a cell type which develops in response to stem cell factor. We report here that neonatal and adult rat and human Schwann cells, as well as a transfected rat Schwann cell line and a human Schwannoma line derived from an NF‐1 patient, all produced stem cell factor mRNA and protein. In coculture experiments, surface expression of stem cell factor by neonatal rat Schwann cells was profoundly downregulated by contact with dorsal root ganglion neurites. The receptor for stem cell factor, KIT, was not expressed in normal Schwann cells but was expressed in the human Schwannoma line, suggesting that aberrant KIT expression may form an autocrine loop in certain Schwann cell neoplasias. © 1994 Wiley‐Liss, Inc.