bluuebunny/crossref_metadata_2025_split huggingface dataset:
5′‐flanking sequences of the human HPRT gene direct neuronal expression in the brain of transgenic mice
Authors: Rincón‐Limas D. E. , Geske R. S. , Xue J.‐J. , Hsu C. Y. , Overbeek P. A. , Patel P. I. 
Published: January 2005

AbstractTotal deficiency of hypoxanthine phosphoribosyl‐transferase (HPRT) in humans causes the neurological disorder Lesch‐Nyhan syndrome. The HPRT gene is expressed at basal levels in all tissues but at higher levels in the brain, the relevance and mechanism of which is unknown. To determine if cis‐acting DNA elements play a role in the tissue‐differential pattern of expression, we generated transgenic mice carrying different sequences of the human HPRT (hHPRT) promoter fused to the bacterial lacZ gene. We show that a 1.6 kb fragment of the hHPRT promoter contains essential information to direct β‐galactosidase expression preferentially to the basal ganglia, cerebral cortex, hippocampus, and several other areas of the forebrain. At least two elements within the 1.6 kb fragment appear to be required for neuronal expression. A 182 bp element (hHPRT‐NE) represents one of those sequences and is involved not only in confering neuronal specificity but also in repressing transgene expression in non‐neuronal tissues. These studies provide molecular insight into the mechanism of increased HPRT expression in the brain. © 1994 Wiley‐Liss, Inc.
Glucocorticoids enhance the potency of Schwann cell mitogens
Authors: Neuberger T. J. , Kalimi O. , Regelson W. , Kalimi M. , De Vries G. H. 
Published: January 2005

AbstractPrevious studies have documented that cultured Schwann cells require serum‐containing medium to respond maximally to mitogens. We now report that Schwann cells are able to proliferate to a mitogenic response in a serum‐free defined medium termed oligodendrocyte defined media (ODM). Glucocorticoids are the essential component of ODM which allow Schwann cell proliferation in the serum‐free medium. Charcoal treatment of the fetal calf serum decreases the mitogenic potency of the axolemma‐enriched fraction (AEF) by 50%. The addition of 2 μM hydrocortisone to charcoal‐treated fetal calf serum restores 75% of the lost mitogenicity. These observations are consistent with the view that glucocorticoids present in fetal calf serum are potent co‐mitogens essential for AEF‐induced Schwann cell proliferation. The synthetic glucocorticoid, dexamethasone, is a more potent co‐mitogen than hydrocortisone, with a maximal effect at concentrations less than 10 nM. In contrast, other steroids including aldosterone, progesterone, testosterone, and 17β‐estradiol have no effect on enhancing the mitogenic response of Schwann cells to the AEF. The glucocorticoid antagonists RU 486 and dehydroepiandrosterone (DHEA), but not the antiestrogenic compound tamoxifen, block AEF‐induced Schwann cell proliferation. These results suggest that glucocorticoid‐induced Schwann cell proliferation is mediated through a glucocorticoid receptor (GR) mechanism. We detected immunoreactivity to the GR in the cytoplasm, but not in the nuclei of Schwann cells grown in ODM lacking dexamethasone. The addition of 100 nM dexamethasone to these cultures resulted in immunoreactivity in the nucleus. This data suggests that glucocorticoids working through the GR are potent co‐mitogens for Schwann cell proliferation. © 1994 Wiley‐Liss, Inc.
13C NMR spectroscopy study of cortical nerve cell cultures exposed to hypoxia
Authors: Müller T. B. , Sonnewald U. , Westergaard N. , Schousboe A. , Petersen S. B. , Unsgård G. 
Published: January 2005

AbstractPrimary cultures of cerebral cortical GABA‐ergic neurons growing on top of a preformed layer of astrocytes (co‐cultures) were incubated with [1‐13C]glucose and exposed to a low oxygen atmosphere (2% O2) for 17 hr. 13C, 1H, and 13P nuclear magnetic resonance (NMR) spectroscopy was performed on perchloric acid (PCA) extracts of cells and of media collected from these cultures. In the control groups incorporation of 13C label into glutamine, citrate, and lactate could be demonstrated in both cell extracts and culture media. Labeled GABA and glutamate were only observed in cell extracts. During hypoxia high energy phosphates decreased but lactate production and glucose consumption increased. There was a decreased amount of citrate and glutamine in cell extracts and media of the hypoxic co‐cultures. There was a change in distribution of the 13C label within the GABA molecule, with an increase of labeling in the C‐2 position. This change in 13C distribution was not found in glutamine present in the media where it is a precursor for GABA in neurons. Instead a decrease in the corresponding C‐4 position was observed. These results suggest that energy depletion during hypoxia leads to reduced export from the astrocytic tricarboxylic acid (TCA) cycle as demonstrated by a decreased amount of citrate and changed distribution of 13C in glutamine. The change in the distribution of label in GABA from cell extracts as compared to glutamine in the medium may indicate that neurons are synthesizing GABA using precursors supplied from their own TCA cycle and not from precursors supplied by astrocytes.
Lesion‐specific pattern of immunocytochemical distribution of growth‐associated protein B‐50 (GAP‐43) in the cerebellum of weaver and PCD‐mutant mice: Lack of B‐50 involvement in neuroplasticity of Purkinje cell terminals?
Authors: Bäurle J. , Oestreicher A. B. , Gispen W. H. , Grüsser‐Cornehls U. 
Published: January 2005

AbstractThe growth‐associated protein B‐50 (GAP‐43) is thought to play a major role in the development and regeneration of neurons. The participation of B‐50 in neuronal plasticity is well documented, especially for monoaminergic systems. However, such an important role for B‐50 in GABAergic systems has not been substantiated to date. This study was performed to obtain detailed information about the identity of B‐50 immunopositive axons and terminals in the cerebellum and to test the involvement of this protein during plastic changes as observed in the projections of GABAergic Purkinje cells to the lateral vestibular nucleus (LVN). For this purpose mutant mice with specific cerebellar cell loss were used. Weaver mutants (B6CBA wv/wv), PCD‐mutants (B6C3Fe pcd/pcd), and their corresponding wild‐type mice were investigated with immunocytochemical and immunoblot procedures at the age of 8‐‐23 days and 5‐‐6 months using polyclonal and monoclonal antibodies to B‐50. Substantial differences in B‐50 distribution wee detected between normals and mutants and between young and adult animals. These results demonstrate that the labeling of B‐50 is mainly related to the outgrowth of parallel fibers and to a minor degree on the ingrowth of non‐GABAergic cerebellar afferents. There was no immunocytochemical indication that B‐50 is related to Purkinje cells or accompanies the plasticity of the GABAergic innervation of the LVN. © 1994 Wiley‐Liss, Inc.
Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis
Authors: Bauer J. , Sminia T. , Wouterlood F. G. , Dijkstra C. D. 
Published: January 2005

AbstractThe EDI monoclonal antibody recognizes an antigen in lysosomal membranes of phagocytes. The expression of this antigen in cells increases during phagocytic activity. Here we describe the expression of ED1‐immunoreactivity during the various stages of both acute (monophasic) and chronic relapsing experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. During the first attack of acute and chronic relapsing EAE, ED1‐immunoreactivity was present in macrophages and in cells which displayed morphologic features of activated microglial cells (i.e., cells with thick short processes). At the ultrastructural level these cells were seen to contain phagocytosed myelin structures in lysosomes. ED1‐immunoreactivity in these cells was present in the cytoplasm near lysosomes. During the remission phase of acute EAE and the relapse phase of chronic relapsing EAE, ED1‐positive cells with dendritic morphology not only were present in or nearby lesions, but were also found at sites distant from lesions throughout large parts of the brain. These cells had a morphology comparable to microglial cells in normal brain. A major difference between animals which were in remission and animals which on day 25 were suffering from a relapse, was that the latter showed the presence of lesions with darkly stained round ED1‐positive macrophages and activated microglial cells. These results indicate that during a relapse, newly recruited bloodborne macrophages infiltrate the brain and, together with activated lymphocytes and microglial cells, recommence a new demyelination process. © 1994 Wiley‐Liss, Inc.
Migration of genetically labeled glioma cells after implantation into murine brain
Authors: Yamada M. , Shimizu K. , Miyao Y. , Hayakawa T. , Nakajima K. , Nakahira K. , Nakagawa H. , Mikoshiba K. , Ikenaka K. 
Published: January 2005

AbstractMurine RSV‐M glioma cells were genetically labeled with a retroviral BAG vector carrying the Escherichia coli β‐galactosidase gene. The X‐gal‐positive stable cell line RSV‐M/BAG was obtained by the FDG‐FACS method. To examine the behavior of glioma cells in the brain, we homografted RSV‐M/BAG cells into the brain of C3H/HeN mice as cell suspensions. Individual grafted glioma cells were easily detected by histochemical staining for B‐galactosidase (β‐gal). Three days after grafting, the β‐gal‐positive cells were mainly found in the subependymal zone of the lateral ventricle. In addition, some solitary labeled cells were found at locations distant from the injection sites. On the seventh day after implantation, tumor masses were observed and graft‐derived glioma cells were migrating bilaterally along the fibers in the corpus callosum. Other labeled cells extended into the brain parenchya via the perivascular (Virchow‐Robin) spaces. Rapid and extensive migration of individual glioma cells was thus clearly demonstrated by intracerebral transplantation of RSV‐M/BAG cells. © 1994 Wiley‐Liss, Inc.
Intracranial infusion of monoamine‐activated α2‐Macroglobulin decreases dopamine concentrations within the rat caudate putamen
Authors: Hu Y.‐Q. , Dluzen D. E. , Koo P. H. 
Published: January 2005

AbstractMonoamine‐activated α2‐macroglobulin (α2M) has been shown to inhibit choline acetyltransferase in basal forebrain neurons as well as neurotrophin‐dependent neuronal functions. The objective of this study was to determine whether monoamine‐activated α2M can affect the caudate putamen (CP) dopaminergic system in vivo. Male rats received intracranial infusions of methylamine‐activated α2M (0.6 nmole) and contralateral infusions of its vehicle, phosphate‐buffered saline (PBS). Five days following infusion, the animals were killed, the CP dissected into three rostral‐caudal segments, and assayed for dopamine (DA) using a high‐performance liquid chromatography system. Within the two rostral CP segments (the approximate site of cannula placement), statistically significant (26%) reductions of DA concentrations were obtained on the α2M‐infused side of the CP with 90–100% of the animals showing decreases. At a more distal (caudal) site of the CP, DA concentrations showed only an insignificant (12%) reduction. No differences in DA concentrations between sides infused with bovine serum albumin versus PBS or from olfactory tubercle samples were obtained in these animals. These results demonstrate that monoamine‐activated α2M is capable of producing significant degeneration of the nigrostriatal dopaminergic system in vivo and suggest that this factor may play a role in age‐related neurodegenerative disorders such as Parkinson's disease. © 1994 Wiley‐Liss, Inc.
The interleukin‐1‐induced increase of substance P in sympathetic ganglia is not mediated by ciliary neurotrophic factor
Authors: Ding M. , Hart R. P. , Shadiack A. M. , Jonakait G. M. 
Published: January 2005

AbstractInterleukin‐1 (IL‐1) induction of substance P (SP) in cultured sympathetic ganglia requires a soluble intermediate molecule that is present in IL‐1 conditioned medium (IL‐1CM). One of the required intermediates is leukemia inhibitory factor (LIF; Shadiack et al., J Neurosci 13:2601–2609, 1993). In the present study we have examined the possibility that ciliary neurotrophic factor (CNTF) is another intermediate involved in the IL‐1 induction of sympathetic SP. CNTF mimics the action of IL‐1CM by raising both SP and choline acetyltransferase activity‐‐‐actions that are blocked by a specific neutralizing antiserum for CNTF. However, IL‐1CM and CNTF differ in their response to depolarizing agents: while KCl (40 mM) blocks the action of IL‐1CM (and LIF), it enhances the action of CNTF. Furthermore, neither CNTF bioactivity nor CNTF protein is detected in IL‐1CM. Neutralizing antiserum to CNTF fails to block the action of either IL‐1 or IL‐1CM, suggesting that neither a soluble nor a membrane‐bound form of the molecule is active in direct response to IL‐1 action. While Northern blots confirm the presence of both CNTF and CNTF receptor mRNA in neonatal ganglia, neither culturing nor IL‐1 treatment alters these mRNA levels. These data taken together suggest that while CNTF is present and possibly active in sympathetic ganglia, it is not a mediator of the IL‐1 induction of SP. © 1994 Wiley‐Liss, Inc.
Poly(ADP‐ribose) polymerase: Early involvement in glutamate‐induced neurotoxicity in cultured cerebellar granule cells
Authors: Cosi C. , Suzuki H. , Milani D. , Facci L. , Menegazzi M. , Vantini G. , Kanai Y. , Skaper S. D. 
Published: January 2005

AbstractGlutamate neurotoxicity is correlated with an increase of cytosolic free Ca2+. In some cell systems, activation of Ca2+ dependent endonucleases or formation of free radicals can damage DNA and activate the chromatin bound enzyme poly(ADP‐ribose) polymerase (pADPRP). We have investigated whether pADPRP may be involved in glutamate neurotoxicity in vitro. Cerebellar granule cells at 12 days in culture when treated with a toxic dose of glutamate (100 μM) showed a rapid and transient increase of poly ADP‐ribose immunoreactivity. Cellular immunostaining was heterogeneous and returned to control levels after washout of glutamate. In the same cell preparations glutamate elicited a marked increase in enzyme protein immunoreactivity which persisted at later times. Non‐toxic doses of glutamate did not affect immunostaining. In another set of experiments, pADPRP mRNA was increased 30 min after glutamate. In order to investigate the role of pADPRP in glutamate‐mediated neurotoxicity, structurally different inhibitors of pADPRP (3‐aminobenzamide, benzamide, 3‐aminophthalhydrazide) and their inactive analogues (benzoic acid and phthalimide) were tested in this model. Addition of the inhibitors to cultures 60 min before and during the 30 min of glutamate treatment prevented neuronal death by 60–100%, assessed 24 hr later. Glutamate‐induced Ca2+ influx was not affected. Inactive analogues failed to afford neuroprotection. These data indicate that not only is pADPRP activated by the early, possibly Ca2+ ‐mediated mechanisms initiated by glutamate, but that it might also actively contribute to the subsequent neuronal death. © 1994 Wiley‐Liss, Inc.
Affinity isolation of neuron‐reactive antibodies in MRL/lpr mice
Authors: Moore P. M. , Joshi I. , Ghanekar S. A. 
Published: January 2005

AbstractAutoantibodies from the MRL/lpr mice react with numerous proteins on neuronal cell surfaces. The purpose of this study was to isolate and characterize a population of autoantibodies reactive preferentially or exclusively with nervous system tissue. Using a purified plasma membrane preparation from brain cortex of balb/c mice coupled to diaminopropylamine agarose gel, we affinity‐isolated antineuronal antibodies from pooled MRL/lpr immunoglobulins. The isolated immunoglobulins reacted with brain cortex plasma membranes and neuroblastoma cells (but not liver, kidney, or fibroblasts) by Western blot and indirect immunofluorescence with confocal microscopy. By Western blot, the epitopes in the brain cortex were proteins of apparent molecular weights 101, 63, 53, 43, 39, and 33, kd; the epitopes in the neuroblastoma cells were 63, 57, and 53 kd. Lectin column isolation revealed that the 101 and 63 kd epitopes were glycosylated. Indirect immunofluorescence revealed that the antibodies bound to the cell soma more intensely than to the cell processes of viable cultured neuroblastoma cells. The cell surface localization of this binding was confirmed by confocal microscopy. Within the central nervous system the antibodies bound more intensely to primary cultures of isolated neurons from fetal cortex than to hippocampal or neostriatal cells. With these antibodies we can begin studies of their potential pathogenic effects. © 1994 Wiley‐Liss, Inc.
Patterns of reactivity with anti‐glycolipid antibodies in human primary brain tumors
Authors: Li J. , Pearl D. K. , Pfeiffer S. E. , Yates A. J. 
Published: January 2005

AbstractAntibodies against carbohydrates of three glycolipids were used to determine patterns of immunohistochemical reactivity of histologically identifiable cell subpopulations in 101 human primary brain tumors. For all tumor types fibrillary cells, polar cells, and gemistocytes (commonly seen in astrocytomas and ependymomas) stained more frequently for galactosylcerebroside with mAbO1 than small tumor cells and macrophages. Frequency of staining for sulfatide with mAbO4 was fibrillary > polar > small cells = macrophages. Gemistocytes stained more frequently with mAbO4 than polar cells in all tumors except low grade astrocytomas. These data indicate that tumors classified on histological grounds as astrocytic are often stained with antibodies that recognize oligodendrocytes and their progenitors. Thus, anti‐glycolipid antibodies used in the study of developmental lineage may offer useful tools for classification of human brain tumors. Staining of fibrillary cells, polar cells, and gemistocytes for paragloboside directly with mAb F1H11 was much less common than with mAbO1, but this increased by pretreatment of the tissues with neuraminidase (F1H11 + N). Of particular note was the finding that small tumor cells frequently stained with F1H11 + N. Evidence that these were not macrophages was obtained using double immunostaining with F1H11 + N and anti‐macrophage antibodies. In astrocytomas the frequency of small tumor cells immunostained with F1H11 + N was high grade > anaplastic > low grade, demonstrating a correlation of this tumor cell population with more F1H11 + N may be of value in identifying small, ana‐plastic tumor cells, especially in small biopsies or tissue taken adjacent to the main tumor mass. Copyright © 1994 Wiley‐Liss, Inc.
Developmental expression of protein kinase C isozymes in oligodendrocytes and their differentail modulation by 4β‐phorbol‐12, 13‐dibutyrate
Authors: Asotra K. , MacKlin W. B. 
Published: January 2005

AbstractMyelin gene expression in normal oligodendrocytes (OLG) depends on developmentally regulated protein kinase C (PKC) enzyme activity (Asotra and Macklin: J Neurosci Res 34:571–588, 1993). We studied the developmental expression of the Ca++‐dependent PKC‐α, ‐βI, ‐βII and ‐γ isozymes, and the Ca++‐independent PKC‐δ, ‐ϵ, ‐ζ and ‐η isozymes in enriched rat brain OLG cultures. In A2B5+ O‐2A progenitors, only PKC‐δ, PKC‐ϵ and PKC‐ζ were detected immunocytochemically. In 04+ proligondendrocytes, PKC‐βI, ‐δ and ‐ζ were expressed moderately and low levels of PKC‐α and ‐ϵ were detected. GD3+ OLG, GC+ OLG and MBP+ OLG showed increased levels of PKC‐α, ‐βI, ‐δ and ‐ζ isozymes. PKC‐βII, ‐γ and ‐η were poorly expressed in OLG. On immunoblots, PKC‐α was present early and increased continually up to 18 days but PKC‐βI increased until 12 days in cultured OLG. High levels of PKC‐δ, PKC‐ϵ and PKC‐η, the most abundant PKC isozymes in OLG, were maintained up to 12 days and were then slightly reduced. Interestingly, relatively high levels of PKC‐α, PKC‐βI, PKC‐βII, PKC‐γ and PKC‐ϵ isozymes were detected in purified myelin membrane although greater levels of PKC‐δ were found in OLG than in purified myelin. Thus, most of the PKC isozymes found in cultured OLG were also present in myelin, although at different levels. Treatment with 50 nM 4β‐phorbol‐12,13‐dibutyrate (PDB) caused a delayed downregulation of PKC‐δ levels after 8 hr without modulating the expression of other PKC isozymes in 1‐day OLG; in the 3‐day‐old and 6‐day‐old OLG, PDB downmodulated PKC‐βI, ‐δ and ϵ isozymes with only a minor effect on PKC‐α and no reduction in PKC‐ζ. Induction or downmodulation of individual PKC isozymes by phorbol esters appears to depend on the differentiation state of OLG. These data suggest that PKC‐βI, ‐δ and ‐ϵ isozymes have an important function in different cellular events of OLG differentiation. We conclude that the PKC‐dependent modulation of myelin gene expression in OLG results predominantly from the Ca++‐dependent PKC‐βI isozyme activity and the Ca++‐independent PKC‐δ and PKC‐ϵ activities in a cell differentiation state‐dependent manner. Because of continuous presence of PKC‐ζ isozyme in all the OLG phenotypes and its regulation by a mechanism unlike that for the regulation of other PKC isozymes, PKC‐ζ may have a unique role in OLG function. © 1994 Wiley‐Liss, Inc.
Deafferentation removes calretinin immunopositive terminals, but does not induce degeneration of calbindin D‐28k and parvalbumin expressing neurons in the hippocampus of adult rats
Authors: Beck K. D. , Hefti F. , Widmer H. R. 
Published: January 2005

AbstractUnilateral combined transections of the fimbriafornix and angular bundle in adult Fischer 344 rats were used to study the effects of deafferentation on hippocampal expression of calretinin, calbindin D‐28k, and parvalbumin. Reflecting the widespread degeneration of synaptic contacts, immunostaining for glial fibrillary acidic protein 6 days after the lesions was increased in lacunosum‐molecular and oriens layers of CA1, 2, and 3 in ipsi‐ and contralateral hippocampus and in the ipsilateral dentate gyrus outer molecular layer. At 21 days the immunoreactivity had decreased to control levels except for a still slightly increased signal in the oriens layer of CA1‐3. At 6 and 21 days after the combined lesions the numbers of hippocampal neurons containing calretinin, parvalbumin, and calbindin D‐28k was unaltered. The combined lesions abolished calretinin containing terminals in the dentate gyrus inner molecular layer on the deafferentated side. This could be reproduced by single unilateral fimbria‐fornix transections, suggesting that the axons of these calretinin positive terminals project to the hippocampus through the fimbria‐fornix. The most likely origin of the calretinin positive terminals are neurons in the supramammillary hypothalamic nucleus. Our findings demonstrate that the extensive lesion‐induced synaptic rearrangements in the adult hippocampus do not induce degeneration of hippocampal neurons expressing calretinin, calbindin D‐28k, and parvalbumin, but do remove calretinin containing terminals which reach their targets in the hippocampus through the fimbria‐fornix. © 1994 Wiley‐Liss, Inc.