bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in c‐fos expression in the dorsal column‐medial lemniscal system following dorsal column lesions
Authors: Riley L. A. , Bernstein J. J. 
Published: January 2005

AbstractTransection of the hindlimb dorsal column fibers leads to a partial deafferentation of the neurons of the nucleus gracilis, the first relay of the ascending dorsal column‐medial lemniscal (DC‐ML) neural network. In response to the deafferentation, a synaptic renewal cycle is initiated and the neurons of the nucleus gracilis atrophy. The present study examines the molecular changes that occur in synaptic relays of the ascending DC‐ML following a hindlimb dorsal column transection. Rats were sacrificed 0.5, 1, 24, or 72 hours postlesion. Steady‐state levels of mRNA coding for c‐fos were significantly elevated only at 24 hours postlesion in caudal dorsal medulla, which contains the nucleus gracilis. The increased c‐fos is neuronal in origin since there is an increased level of c‐fos immunoreactivity in both the cluster neurons and the interneurons of the nucleus gracilis. In the third relay of the DC‐ML system, the somatomotor cortex, levels of c‐fos mRNA were significantly decreased 72 hours postlesion. These data indicate that lesions of the hindlimb dorsal column fibers have transneuronal effects on gene expression that extend to at least the third synaptic relay in the DC‐ML system. © 1995 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
CNS myelinogenesis in vitro: Time course and pattern of rat oligodendrocyte development
Authors: Asou Hiroaki , Hamada K. , Miyazaki T. , Sakota T. , Hayashi K. , Takeda Y. , Marret S. , Delpech B. , Itoh K. , Uyemura K. 
Published: January 2005

AbstractOligodendrocyte precursor cells that develop into myelin‐forming cells of the central nervous system (CNS) were cultured from newborn rat brain to study how they proliferate and differentiate in normal conditioning medium, and their cell development was characterized by scanning electron microscopy (SEM) observation and immunocytochemical studies.We have identified A2B5‐negative pre‐O2A progenitor cells (so‐called “type‐1” oligodendrocytes) in the secondary cultures on the astrocyte feeder layer. These cells are very small (diameter: 3.5 μm), round, and glossy, and develop into the process‐bearing O2A progenitor cells (called “type‐2” oligodendrocytes), which also express myelin basic protein (MBP) both in the cell body and in their cell processes. Finally, they develop into mature oligodendrocytes (called “type‐3” oligodendrocytes). After MBP expression is elicited in these cells and MBP accumulates in the cell process in the area in contact with the axon, these cells are capable of forming the myelin sheath. Therefore, we examined the mechanism of myelin‐sheath formation of “type‐3” oligodendrocytes using video time‐lapse movies, and demonstrated that these cells initially sent out processes to search for axons several times before the onset of myelination. Then thick filopodia extended towards the axon, and at the same time, the axonal part of neuron moved forward. Finally the ruffling lamellipodial parts wrapped up the axon similarly to a transverse wave with the secured thick filopodial process on the axon acting as scaffolding. These results suggest that our experimental systems are useful in studying normal oligodendrocyte development and their cellular biochemistry, as well as investigating the mechanism of myelin formation by oligodendrocytes. © 1995 Wiley‐Liss, Inc.
Glutamate‐activated ionic currents in cultured astrocytes from trout: Evidence for the occurrence of non‐N‐methyl‐D‐aspartate receptors
Authors: Clasen T. , Jeserich G. , Krüppel T. 
Published: January 2005

AbstractGlutamate‐induced currents were recorded from cultured trout astrocytes with the whole‐cell variation of the patch‐clamp technique. Ninety percent of the tested cells were directly depolarized by the amino acid neurotransmitter in a concentration‐dependent manner. The depolarizing effect was due to an inward current that reversed near 0 mV and was accompanied by a noise increase, indicating the opening of an ion channel. Ion substitution experiments revealed that the glutamate‐induced current was mainly carried by sodium ions but not chloride or calcium ions. The glutamate‐induced response could be mimicked by the neuronal glutamate receptor subtype agonists kainate and quisqualate, while N‐methyl‐D‐aspartate was without detectable effect. © 1995 Wiley‐Liss, Inc.
Death of septal cholinergic neurons produced by chronic exposure to glutamate is prevented by the noncompetitive NMDA receptor/channel antagonist, MK‐801: Role of nerve growth factor and nitric oxide
Authors: Michel P. P. , Agid Y. 
Published: January 2005

AbstractTo study the sequence of degenerative events possibly associated with cholinergic cell death in Alzheimer's disease, septal cholinergic neurons derived from rat embryonic brains were exposed to chronic excitotoxic stress by glutamate. Counts of choline acetyltransferase (ChAT)‐immunopositive neurons and measurement of ChAT activity revealed that concentrations of glutamate on the order of 70 μM killed 50% of cholinergic neurons after 24 hr of treatment. Neurotoxic effects were not aimed at cholinergic neurons specifically, since other populations of cells present in these cultures were also affected at similar concentrations. The noncompetitive N‐methyl‐D‐aspartate (NMDA) receptor channel antagonist MK‐801 (10 μM) abolished acute neuronal swelling and rescued from late degeneration both cholinergic and non‐cholinergic cells when concentrations of glutamate up to 500 μM were added to the cultures. Protective effects declined progressively with increasing concentrations of the amino acid, even when MK‐801 was raised to its highest nontoxic levels, e.g., 50 μM. The kainate/quisqualate receptor antagonist CNQX provided no protection alone or in combination with MK‐801. Nerve growth factor (NGF), used in standard culture conditions to stimulate the expression of the cholinergic phenotype, was shown not to influence excitotoxic neurodegenerative changes. Several observations suggested that nitric oxide (NO) may act as an intercellular messenger of NMDA‐mediated cell death in septal cultures: (1) Most of the cholinergic neurons contained the NO synthase enzyme as characterized by NADPH‐diaphorase (NADPH‐d) staining; (2) sodium nitroprusside (SNP) [a chemical with the ability of generating NO] was capable of mimicking some of the aspects of the glutamate‐induced degenerative process; (3) the rise in cyclic GMP which was observed in the presence of toxic levels of glutamate and which is usually taken as an index of NO production, was antagonized by MK‐801 and by the inhibitor of the NO synthase enzyme, L‐NOARG. Yet, the fact that L‐NOARG and its congener, L‐NAME, were ineffective in preventing glutamate‐induced neurodegenerative changes in our culture system did not substantiate our working hypothesis. Altogether these results suggest that glutamate‐induced cholinergic neuronal death is the consequence of an overstimulation of NMDA receptors and that neither NGF nor NO plays a key role in the degenerative process. © 1995 Wiley‐Liss, Inc.
Regeneration of specific nerve cells in lesioned visual cortex of the human brain: An indirect evidence after constant stimulation with different spots of light
Authors: Potthof R. D. 
Published: January 2005

AbstractThe defective parts of the visual field of two braininjured patients were stimulated with different spots of light. There is evidence for at least five independent visual functions which can be restored due to constant stimulation of the blind part of the visual field: (1) The constant stimulation of the blind part of the visual field with spots of white light leads to an increase of the visual field for the perception of white light only. (2) The constant stimulation with spots of light of different wavelengths leads to an increase of the visual field for different color perception. To enlarge the visual field for the perception of the color red, a light stimulus with the wavelength of 656 nanometers (nm) was used; for the visual field for the perception of the color green 525 nm; for yellow 578 nm; and for blue 450 nm. (3) The constant stimulation of the blind visual field with black and white light bars of different orientations and constellations leads to an increase of the foveal acuity and an improvement of form perception in the periphery of the visual field.The results suggest that the recovery of visual functions, different color perception and form perception, may depend upon neuronal regeneration in the human visual cortex; regeneration occurs with adequate and constant stimulation of its specific neurons. © 1995 Wiley‐Liss, Inc.
Site‐directed mutagenesis of human CNTF: Functional analysis of recombinant variants
Authors: Thier M. , Simon R. , Krüttgen A. , Rose‐John S. , Heinrich P. C. , Schröder J. M. , Weis J. 
Published: January 2005

AbstractCiliary neurotrophic factor (CNTF), interleukin‐6 (IL‐6), leukemia inhibitory factor (LIF), and oncostatin M (OSM) share functional properties, a predicted common helical framework, and partially identical receptor components. CNTF is a survival promoting factor for various types of neurons in vitro and in vivo. In the present study, structural features essential for the biological function of human CNTF were investigated. Several recombinant CNTF variants were constructed by PCR and expressed in E.coli. Their survival promoting activities were determined using cultures of embryonic chick and newborn rat dorsal root ganglion cells. Deletion of 14 N‐terminal and 18 C‐terminal amino acids significantly increased bioactivity compared to wild‐type (wt) CNTF. Further truncation of the CNTF molecule at the N‐ or C‐terminus resulted in a significant reduction or complete loss of activity. Substitution of two amino acids (Lys154Glu and Trp157Pro) abolished the survival promoting effect. Recently described analogous substitutions in IL‐6 had resulted in a partial IL‐6 receptor antagonist. However, the double substitution variant had no significant inhibitory effect on wtCNTF activity in assays with both wt and mutant factor. The CNTF variants constructed had almost identical effects on both chick and rat neurons indicating a close similarity of the avian and the mammalian CNTF receptor complex. The present results also demonstrate that a core segment of the CNTF molecule is indispensable for biological function. Analogous segments important for activity have already been identified in the related molecules IL‐6, LIF, and OSM. Thus, our data confirm the close structural relationship of CNTF to these “neuropoietic” cytokines. In addition, they demonstrate that site‐directed mutagenesis of recombinant human CNTF can yield molecules which show increased survival promoting activity on mammalian neurons. © 1995 Wiley‐Liss, Inc.
Axonal atrophy in aging is associated with a decline in neurofilament gene expression
Authors: Parhad I. M. , Scott J. N. , Cellars L. A. , Bains J. S. , Krekoski C. A. , Clark A. W. 
Published: January 2005

AbstractNeurofilaments (Nfs) are major determinants of axonal caliber. Nf transcript levels increase during development and maturation, and are associated with an increase in Nf protein, Nf numbers, and caliber of axons. With aging there is axonal atrophy. In this study we asked whether the axonal atrophy of aging was associated with a decline in Nf transcript expression, Nf protein levels, and Nf numbers. Expression of transcripts for the three Nf subunits was evaluated in dorsal root ganglia (DRG) of Fischer‐344 rats aged 3–32 months by Northern and in situ hybridization. There was an approximately 50% decrease in Nf subunit mRNA levels in DRG of aged (>23 months) as compared to young and mature (3 and 12 months) rats, whereas expression of another neuronal mRNA, GAP‐43, showed no decline. Western analysis showed a corresponding decrease in Nf subunit proteins and no decline in GAP‐43. Morphometric analysis showed a 50% decrease in Nf numbers within axons. The decrease in Nf gene expression and Nf numbers was accompanied by a decrease in cross‐sectional area and circularity of all myelinated fibers, with the largest fibers showing the most marked changes, and a shrinkage in the perikaryal area of large neurons. Furthermore, we found a concomitant decrease in the expression of transcripts for the nerve growth factor receptors trkA and p75 with aging. Although the mechanisms leading to the decrease in Nf gene expression with aging are not known, a decrease in the availability of growth factors, or the neuron's ability to respond to them, may play a role in this process. © 1995 Wiley‐Liss, Inc.
Bilateral gliosis in unilaterally lesioned septohippocampal system: Changes in GFAP immunoreactivity and content
Authors: Jegliński W. , Koczyk D. , Zaremba M. , Oderfeld‐Nowak B. 
Published: January 2005

AbstractUnilateral damage to the lateral fimbria led to a bilateral gliosis in the septum and hippocampus. The gliosis was manifested by an increase in GFAP staining, accompanied by an increased number of glial fibrillary acidic protein (GFAP)(+) cells and GFAP content; the latter however was not visible in the contralateral septum. In general, the contralateral reaction appeared weaker than the ipsilateral one.The pattern of contralateral increase in GFAP‐immunoreactivity (IR) matched almost exactly that observed on the ipsilateral side in the hippocampus (the most evident increase was seen in the oriens and pyramidal layers of cornu Ammonis 3 and in polymorphie area of gyros dentatus). In the septum the bilateral increase in GFAP‐IR was mainly visible in the dorsolateral quadrant of the structure; however in the ipsilateral side it spread over the whole half of the structure.The astrocytic responses in the septum and hippocampus were not equivalent: they differed mainly with regard to the increase of GFAP(+) cells (over 300% of control in the anterior part of the septum and only about 120% in the dorsal hippocampus). The differences between astrocytic response in the septum and hippocampus were also manifested by different relations between the percentage increases of other gliotic indices: GFAP‐IR and GFAP content.Various possibilities that may account for the occurrence of contralateral gliosis are discussed, the most plausible being the contribution of interhemispheric and intraseptal links and the action of some diffusible agents. We suggest that bilateral gliosis may have an impact on compensatory postlesion processes, possibly by providing trophic support to impaired neurons. © 1995 Wiley‐Liss, Inc.
Glutamate‐induced antigenic changes of phospholipase C‐δ in cultured cortical neurons
Authors: Shimohama S. , Akaike A. , Tamura Y. , Matsushima H. , Kume T. , Fujimoto S. , Takenawa T. , Kimura J. 
Published: January 2005

AbstractPhosphoinositide‐specific phospholipase C (PLC) is a key enzyme in signal transduction. It was previously demonstrated that an antibody to an isozyme of PLC, PLC‐δ, produces intense staining of neurofibrillary tangles (NFT), the neurites surrounding senile plaque (SP) cores and neuropil threads in the brains of patients with Alzheimer's disease (AD). Although the etiology of neuronal degeneration in AD is still to be defined, excitotoxic glutamate might be a candidate. In the present study, an anti‐PLC‐δ antibody was used to examine the influence of glutamate on PLC‐δ immunoreactivity in cultured rat cortical neurons. Exposure to glutamate caused the death of cultured cortical neurons and exhibited increased immunostaining with the anti‐PLC‐δ antibody. Subtoxic doses of glutamate also increased PLC‐δ immunoreactivity in a dose‐dependent manner. Both glutamateinduced neuronal degeneration and the increases in PLC‐δ immunoreactivity were prevented by removal of extracellular Ca2+ or the application of an N‐methyl‐D‐aspartate (NMDA) receptor antagonist, MK801. The glutamate‐induced increase in PLC‐δ immunoreactivity was also prevented by Nω‐nitro‐Larginine, a nitric oxide (NO) synthase inhibitor. These results suggest that NO formation secondary to Ca2+ influx by NMDA receptor activation leads to similar modifications of PLC‐δ to those seen in AD. © 1995 Wiley‐Liss, Inc.
Studies on T‐cell receptors involved in experimental autoimmune encephalomyelitis using the complementary peptide recognition approach
Authors: Xian C. J. , Simmons R. D. , Willenborg D. O. , Vandenbark A. A. , Hashim G. A. , Carnegie P. R. 
Published: January 2005

AbstractBased upon Blalock's complementary recognition approach, a complementary or antisense peptide (CP) was designed to the experimental autoiramune encephalomyelitis (EAE) epitope peptide, rat myelin basic protein (MBP) peptide 72‐82. This peptide (EAE CP) was shown to have some sequence similarities to T‐cell receptors (TCR) and MHC II molecules in a sequence homology search. Solid‐phase binding as‐says demonstrated specific and high affinity binding (3 and 4 μM) between the EAE CP and the rat and guinea pig EAE epitope peptides (Rt72‐82 and Gp69‐82), respectively. This EAE CP was also found to be immunogenic in rats in an ear swelling test for delayed type hypersensitivity (DTH) reactions and an ELISA for antibody responses. However, a rabbit antibody generated to EAE CP was shown to be unable to stain the Vβ8+ EAE susceptible T‐cells in immunofluorescence analyses. This EAE CP was also used in attempts to down‐regulate EAE and the results showed that prior immunization with EAE CP in complete Freund's adjuvant could not prevent the Lewis rats from developing EAE. Although the data on sense‐antisense peptide interaction were positive and the EAE CP was immunogenic, the inability of EAE CP to regulate EAE indicates that the CP approach may not be generally applicable. © 1995 Wiley‐Liss, Inc.
Mitogn induced proliferation of isolated adult mouse schwann cells
Authors: Zhang B. T. , Hikawa N. , Horie H. , Takenaka T. 
Published: January 2005

AbstractThe proliferation of neonatal Schwann cells (SCs) in response to mitogenic agents has been well analyzed in vitro, but a limited range of mitogens have been defined. We investigated whether three identified neonatal SC mitogens [glial growth factor (GGF), platelet‐derived growth factor BB (PDGF‐BB), and basic fibroblast growth factor (bFGF)] are required to stimulate mitosis of adult SCs. Adult SCs were isolated from mouse sciatic nerves by mechanical and chemical dissociation, following three experimental steps: (1) culturing the dissociated cells for 24 hr in 10% FCS‐F12 medium, (2) culturing these cells in serum‐free medium for the next 48 hr, and (3) purifying adult SCs by differential adhesion. We describe a new method for preparation of SCs from peripheral nerves of adult mouse that provides 99.5% pure SCs populations at cell yields of greater than 3 × 103 cells/mg of starting nerve wet weight within 5 culture days. Although mitosis of SCs in culture in response to mitogens requires the presence of serum, the complex nature of serum renders difficult a complete analysis of mitogens required for SCs DNA synthesis, so we examined the proliferating response of adult SCs to GGF, PDGF‐BB, and bFGF in serum‐free medium. GGF alone had mitogenicity for adult SCs in a dose‐dependent manner, and synergistic activation coupling with forskolin was not observed. Neither PDGF‐BB nor bFGF was mitogenic for adult SCs when used alone or with forskolin. Measurement of intracellular cyclic AMP levels in SCs cultured with these growth factors showed that cAMP levels were not changed by GGF and bFGF, and PDGF‐BB reduced the cAMP level to half of basal one. This study demonstrated that adult SCs could proliferate without serum factors and forskolin in response to GGF, and adult SCs were activated by GGF through a signal transduction pathway separate from the cyclic AMP‐dependent system. In addition, PDGF‐BB or bFGF has no mitogenic effect on adult SCs under serum‐free conditions. © 1995 Wiley‐Liss, Inc.
Noradrenaline‐induced stimulation of glutamine metabolism in primary cultures of astrocytes
Authors: Huang R. , Hertz L. 
Published: January 2005

AbstractEffects of noradrenaline and of adrenergic subtype specific agonists on the uptake and metabolism of [14C]glutamine and [14C]glutamate in primary cultures of mouse astrocytes have been investigated. The total uptake of radioactivity from extracellular [14C]glutamine into the cells was enhanced during exposure to 100 μM noradrenaline, isoproterenol, or clonidine. This is partly dag to an increased radioactivity in the glutamile pool and partly due to an increased formation of labeled glutamate from glutamine, which had become very marked (66%) after 240 min of incubation. The CO2 formation from labeled glutamine during 4 hr of incubation was enhanced about twofold in the presence of noradrenaline. Ten millimolar amino oxyacetic acid (AOAA), a transamination inhibitor, had no effect on CO2 formation from glutamine, indicating that the formation of α‐ketoglutarate from glutamate occurs as an oxidative deamination. The stimulation of 14CO2 production from labeled glutamine was at least as large when glucose was deleted from medium, suggesting that the increased 14CO2 formation represents a stimulation of glutamine metabolism as such and is not only a reflection of an increase in oxidative metabolism of glucose and a bidirectional exchange between α‐ketoglutarate and glutamate. The opposite process, incorporation of radioactivity from labeled glutamate into glutamine, was not enhanced in the presence of noradrenaline. The findings suggest that noradrenaline stimulates the rates of glutamine uptake, glutamate synthesis, and CO2 production from glutamine and thus increases energy supply to astrocytes but has no effect on the opposite reaction, i.e., glutamine formation from glutamate, a reaction of importance for neuronal‐astrocytic interations. © 1995 Wiley‐Liss, Inc.
Early neuroblasts are pluripotential: Colocalization of neurotransmitter and neuropeptides
Authors: Kentroti S. , Vernadakis A. 
Published: January 2005

AbstractThis study was undertaken in order to establish the presence of pluripotential neuroblasts in the developing chick CNS. This has been suggested by our previous observations that expression of emerging neuronal phenotypes in the chick embryo CNS is affected by exposure to neurotrophic substances (i.e., GHRH, SRIF, NGF, EGF, muscle‐derived factors) or neurotoxins such as ethanol. We have proposed that one mechanism whereby these substances elicit their effects is by shifting phenotypic expression in populations of pluripotential neuroblasts. In order to establish the presence of significant populations of pluripotential neuroblasts, cultures obtained from 3‐day‐old whole chick embryos (E3WE) were doublestained with antibodies to markers specific for four neuronal phenotypes in various permutations. Cultures at 6 DIV were tested for the presence of tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), γ‐aminobutyric acid (GABA), and somatostatin (SRIF) alone, and in various combinations. We observed a colocalization of all phenotypic markers within neuronal perikarya and processes in more than fifty percent of neuronal cells in these cultures. These data suggest that developing neuroblasts at this stage of embryogenesis possess the machinery necessary to adopt multiple neuronal phenotypes. The colocalization of neurotransmitter proteins in early neuroblasts (60 hr of embryogenesis) supports the recent concept that these substances themselves may influence phenotypic expression and also supports our idea that microenvironmental factors (i.e., ethanol, growth factors) provide signals which affect emerging phenotypes. © 1995 Wiley‐Liss, Inc.