bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pertussis toxin provides evidence for two independent signalling pathways leading to the activation of the nerve growth factor gene
Authors: Wion D. , Neveu I. , Jehan F. , Brachet P. 
Published: May 2005

AbstractIncreased expression of the nerve growth factor (NGF) gene may be obtained by treating L929 fibroblasts with serum, phorbol 12‐myristate 13‐acetate (PMA), or 1,25‐dihydroxyvitamin D3 (1,25‐(OH)2 D3). The possible involvement of GTP‐binding proteins (G proteins) in these regulatory events was monitored by exposing the cells to pertussis toxin (PT), a compound known to inactivate several types of G proteins by ADP ribosylation. Measurements of the I pool of NGF mRNA by Northern blot analysis, and quantification of the factor secreted by the cells with a double‐site ELISA assay, indicate that pretreatment with PT decreases by about 60% the effect of serum on the levels of NGF transcript and secreted factor. This effect is accompanied by a corresponding decrease of the expression of c‐fos gene, which takes place soon after the addition of serum to the cells. In contrast, PT had no effect on the basal level of NGF mRNA found in cells maintained in serum‐free medium or in cells stimulated with PMA or 1,25‐(OH)2D3. These results indicate that some serum factor(s) acts via plasma membrane receptors able to interact with PT‐sensitive G proteins to modulate NGF gene expression. In contrast, 1,25‐(OH)2D3 appears to mediate its action through a different signalling pathway, which is likely to require its cytosolic receptor, and is independent of PT‐sensitive G protein and c‐fos induction. PMA is thought to directly activate enzymes of the protein kinase C family, and would therefore bypass the step involving activation of these enzymes by a G‐proteindependent pathway. These results suggest that a dys function in the G protein(s) and c‐fos pathway involved in the regulation of NGF gene could lead to neuropathological processes by altering the expression of the NGF gene. In addition, 1,25‐(OH)2 D3, in light of its ability to bypass these pathways, could be of potential interest in the treatment of neurodegenerative diseases.
Sequential effects of astroglial‐derived factors on neurite outgrowth: Initiation by protease inhibitors and potentiation by extracellular matrix components
Authors: Shea T. B. , Beermann M. L. , Nixon R. A. 
Published: May 2005

AbstractAstroglial‐conditioned medium (GCM) induced two distinct, but intimately related, phases of neuritogenesis in NB2a/dl neuroblastoma cells—a “rapid‐outgrowth,” unstable phase, and a delayed, relatively stable phase, which are apparently regulated by glial‐derived protease inhibitors and laminin, respectively. The initial rapid outgrowth (<4 hr) may be mediated by inhibition of a thrombin‐like protease, present as a serum component and/or adsorbed to the outer neuronal surface, since (1) a similar effect was obtained by serum removal or by adding the specific thrombin inhibitor, hirudin; (2) exogenous thrombin inhibited the rapid outgrowth of neurites by GCM; and (3) cell‐free enzyme assays confirmed the presence of thrombin‐inhibitory activity in GCM. Although neurites induced by removal of serum removal or hirudin addition are rapidly resorbed following serum replenishment or hirudin depletion, GCM‐induced neurites continued to elongate after GCM removal, indicating that GCM contained additional neurite‐promoting factors. Anti‐laminin antiserum did not inhibit the initial elaboration of neurites by GCM but prevented their continued elongation. Anti‐laminin antiserum had no affect on neurite outgrowth induced by serum deprivation. The more protracted, second phase of neurite outgrowth could also be achieved by the addition of soluble purified laminin to undifferentiated cells. Unlike neurites at 4 hr, neurites at 24 hr were no longer dependent on the protease inhibitors in GCM, since exogenous thrombin no longer caused them to retract. Simultaneous addition of thrombin and anti‐laminin antiserum with GCM had identical inhibitory effects on continued neurite elaboration at 24 hr as did anti‐laminin antiserum without thrombin. We conclude that protease inhibitors present in GCM initiate the rapid elaboration of unstable neurites and that glial‐derived extracellular matrix factors support the continued elaboration of these neurites.
Regional distribution of iron and iron‐regulatory proteins in the brain in aging and Alzheimer's disease
Authors: Connor J. R. , Snyder B. S. , Beard J. L. , Fine R. E. , Mufson E. J. 
Published: May 2005

AbstractIt is well established that iron, which is of considerable importance for normal neurological function, is highly regulated in all organ systems. However, until recently, iron regulation in the nervous system has received little attention. This study quantitatively compares the levels of the major iron‐regulatory proteins, transferrin and ferritin, and iron itself in three cerebral cortical regions of the human brain from material collected at autopsy. Three groups were studied: (1) normal adult (under 65 yr of age), (2) aged (> 65), and (3) Alzheimer's disease. Normally, transferrin is more abundant in white matter than in gray matter. Ferritin is approximately 10 x more abundant than transferrin throughout the brain regions examined and is evenly distributed, as is iron, in the gray and white matter. In Alzheimer's disease transferrin is consistently decreased particularly in the white matter of the various cerebral cortical regions examined whereas the iron and ferritin changes are inconsistent. The observations In this study are consistent with our general hypothesis that iron homeostasis is disrupted in the aging brain and the alterations in iron‐regulatory proteins are exacerbated in Alzheimer's disease. The decrease in transferrin levels could indicate a decreased mobility and subsequent utilization of iron in the brain. Such a decrease in iron availability could play a significant role in neuronal degeneration and increased peroxidative damage known to occur in Alzheimer's disease.
Expression of leucocyte adhesion molecules at the human blood‐brain barrier (BBB)
Authors: Rössler K. , Neuchrist C. , Kitz K. , Scheiner O. , Kraft D. , Lassmann H. 
Published: May 2005

AbstractThe expression of leucocyte adhesion molecules was studied on cerebral endothelia by immunocytochemistry. In peritumoral “normal” brain tissue we found low endothelial expression of 1CAMI, LFA3, CD44, and CD9, whereas VLA1 was present on vessels in high incidence and density. LFAl, CD2, and CR3 were found on intraluminal and parenchymal leucocytes, but were absent on brain vessels. In brain tumors and inflammatory brain lesions, we observed an up‐regulation of endothelial ICAM1 and LFA3 expression, whereas other adhesion molecules on endothelial cells remained unchanged.Within the brain parenchyma, ICAM1 and LFA3 were found on astrocytes and tumor cells; on the contrary, LFA1 was expressed on microglial cells similar to CR3. CD44 and CD9 showed a diffuse neuropil expression in normal and tumoral tissue, whereas VLA1 was not expressed on any parenchymal cells.Our data show that multiple different adhesion molecules are present on blood‐brain barrier endothelium (BBB) under normal conditions and some adhesion molecules are up‐regulated in brain tumors and under inflammatory conditions. The presence of adhesion molecules in the vessel walls as well as on parenchymal cells like astrocytes and microglia may guide inflammatory cells into and through the brain in the course of immune surveillance and inflammation.
Choline acetyltransferase activity in murine thymus
Authors: Tria M. A. , Vantini G. , Fiori M. G. , Rossi A. 
Published: May 2005

AbstractMurine thymus has been demonstrated to contain both cholinergic receptors and acetylcholinesterase activity. In the present study we have investigated the presence of the enzyme choline acetyltransferase in this organ, which is responsible for the synthesis of acetylcholine. Results reported here demonstrate that (1) an appreciable amount of the enzyme is already present in the thymus on the day of birth; (2) its expression is developmentally regulated; and (3) thymic atrophy, induced in young (2‐week‐old) and adult (6‐week‐old) mice by i.p. injection of hydrocortisone for 2 days, is accompanied by significant reduction of choline acetyltransferase activity only in young mice.Altogether these results demonstrate the presence in the murine thymus of functionally relevant markers of the cholinergic system that might interface the interactions between the nervous and immune systems.
Deprenyl reduces the death of motoneurons caused by axotomy
Authors: Salo P. T. , Tatton W. G. 
Published: May 2005

AbstractDeprenyl, a monoamine oxidase B inhibitor, appears to slow the progression of neurological deficits in Parkinson's disease and cognitive decline in Alzheimer's disease. The mechanisms for the slowing of the diseases are unknown. Deprenyl can reduce the death of murine substantia nigra neurons when administered after the neurons are damaged in MPTP parkinsonism by increasing the neurons' survival after they are damaged, rather than by just protecting the neurons against damage by blocking the conversion of MPTP to its active form as was previously thought. The death, of immature motoneurons after separation from their muscle targets by axotomy provides a model for assessing trophically dependent neuronal survival. To determine whether deprenyl can alter the survival of neurons other than those in the substantia nigra, we examined the survival of rat facial motoneurons after axotomy at 14 days of age. Using a combination of immunocytochemistry for choline acetyl transferase and Nissl staining, we found that deprenyl treatment (10 mg/kg every second day) increased by 2.2 times the number of motoneurons surviving 21 days after the axotomy. This finding showed that deprenyl treatment can rescue neurons other than those in the substantia nigra and can compensate in part for the loss of target‐derived trophic support caused by axotomy.
Effects of acidic fibroblast growth factor on higpocampal long‐term potentiation in fasted rats
Authors: Hisajima H. , Saito H. , Abe K. , Nishiyama N. 
Published: May 2005

AbstractEffects of human recombinant acidic fibroblast growth factor (haFGF) on long‐term potentiation (LTP) and the increase of the spike amplitude induced by weak tetanic stimulation were investigated and compared with those of CS23 (modified human basic FGF) in the dentate gyrus of fasted and non‐fasted rats. haFGF didn't influence the LTP induced by the tetanus of 100 pulses at 100 Hz in both 24 hr fasted and non‐fasted rats. On the other hand, the tetanus of 20 pulses at 60 Hz significantly enhanced the amplitude of population spike and facilitated the generation of LTP by the i.c.v. injection of 10 μl of 20–40 μg/ml haFGF in 24 hr fasted rats but not in non‐fasted rats. However, 40 μg/ml CS23 induced LTP when the tetanus of 20 pulses at 60 Hz was applied in both fasted and non‐fasted states. These results suggest that haFGF might be one of the regulating factors of feeding and memory.
Acrylamide exposure preferentially impairs axonal transport of glycoproteins in myelinated axons
Authors: Harry G. J. , Morell P. , Bouldin T. W. 
Published: May 2005

AbstractThe right L5 dorsal root ganglion of adult rats exposed to acrylamide (40 mg/kg body weight/day for nine consecutive days) was injected with either [3H]methionine or [3H]glucosamine. After allowing incorporation into macromolecules and axonal transport to proceed for 5 hr, the distribution of radioactivity in cross sections and longitudinal sections of sciatic nerve was determined by autoradiography. Control and treated animals showed no difference in distribution of label within the sciatic nerve with respect to rapidly transported proteins labelled with [3H]methionine. In control animals the distribution of rapidly transported glycoproteins labelled with [3H]glucosamine was similar to that found for [3H]methionine‐labelled proteins. In contrast, acrylamide‐exposed rats had a very different distribution of labelled glycoproteins; there was a marked paucity of label in the myelinated axons. We interpret this result as indicating that acrylamide preferentially inhibits glycosylation or axonal transport of glycoproteins in neurons bearing myelinated axons.
Cyclic AMP‐induced upregulation of proteolipid protein and myelin associated glycoprotein gene expression in C6 cells
Authors: Ye P. , Kanoh M. , Zhu W. , Laszkiewicz I. , Royland J. E. , Wiggins R. C. , Konat G. 
Published: May 2005

AbstractA Model culture system of C6 rat glioma cells was used to test the involvement of cAMP in the regulation of the myelin PLP and MAG genes. The treatment of cells with isoproterenol (10−5to 10−8M) upregulated the expression of the PLP and MAG genes in a concentration‐dependent manner. The mRNAf or PLP reached a maximum (sevenfold higher than in control cells) after about 12–24 hr, then declined to approximately fourfold over the control level. The response of MAG gene was delayed by at least 36 hr, and the level of MAG mRNA reached a maximum of approximately 48‐fold over the control level on the fourth day in culture. The co‐administration of propranolol blocked the effect of isoproterenol, whereas 10−5M forskolin simulated the effect of isoproterenol, inducating a role of camp in the signal transduction cascades leading to upregulation of the myelin genes. However, the dissimilarity in the timing and the extent of upregulation of the PLP and MAG genes by cAMP‐stimulating agents indicate the existence of different intracellular mechanisms for the activation of these two genes. Cyclocheximide blocked the stimulatory effect of isopoterenol on both the PLP and MAG genes, indicating that the effect of cAMP on the myelin genes is mediated by protein product(s) of other cAMP response gene(s).
Role of amyloid precursor protein (APP): Study with antisense transfection of human neuroblastoma cells
Authors: LeBlanc A. C. , Kovacs D. M. , Chen H. Y. , Villaré F. , Tykocinski M. , Autilio‐Gambetti L. , Gambetti P. 
Published: May 2005

AbstractThe function of amyloid precursor protein (APP) was investigated in human neuroblastoma La‐N‐1 cells by stable transfection with a DNA construct encoding antisense APP mRNA. Levels of APP mRNA, as well as proteins, were reduced by 80–90% in antisense APP transfected (ASAT) cells. ASAT cells exhibited three main features as a result of APP gene expression deprivation: (1) a 30% reduction in cell proliferation, (2) reduced cell adhesion that could be reversed by the addition of La‐N‐1 conditioned media as a source of secreted APP, and (3) a two‐ and four fold increase in neurite‐bearing cells suggesting that; cellular APP may be involved in neurite extension. The first two features confirm previously reported functions for APP in proliferation and adhesion of non‐neuronal cell types but the use of neuroblastoma cells in this study disclose a novel role for cellular APP in neurite extension.
Differentiation of PC12 cells with nerve growth factor is associated with induction of transin synthesis and release
Authors: Fillmore H. L. , Mainardi C. L. , Hasty K. A. 
Published: May 2005

AbstractWe have identified and characterized a calcium‐dependent metalloproteinase which is induced in rat pheochromocytoma cells (PC12 cells) during differentiation with nerve growth factor (NGF). Assays of proteolytic activity in media from differentiated PC 12 cell cultures revealed a NGF‐dependent increase in the activity of a proteinase which has a molecular weight of 62 kDa. Studies using serine, thiol, and metalloproteinase inhibitors demonstrated that the secreted enzyme is a metalloproteinase. Treatment of culture supernatants with aminophenylmercuric acid (APMA), a known activator of metalloproteinases, resulted in a decrease in the molecular weight of the proteinase. Western blot analysis of culture media from NGF‐treated PC12 cells using an antibody directed against a synthetic peptide of rat transin identified this metalloproteinase as transin. Treatment of PC12 cells with acidic and basic fibroblast growth factor (FGF) resulted in distinct morphological changes as well as transin release. Incubation with epidermal growth factor (EGF) did not induce transin release. Dexamethasone inhibited the induction of transin release by NGF. 35S‐methionine labeling and immunoprecipitation of newly synthesized proteins from culture supernatants confirmed that NGF induced the synthesis of this enzyme 8 hr after NGF treatment The NGF‐dependent induction of transin, a calcium‐dependent metalloproteinase which degrades type IV collagen, laminin, and fibronectin suggests that transin may function to degrade the surrounding extracellular matrix during the invasive process of axonal elongation in neuronal development thereby allowing the movement of growth cones and axons toward specific targets.
Novel antigenic determinant expressed in neurons of the dorsolateral hypothalamus in rat and human
Authors: Quinn J. , Eckenstein F. P. , Baughman R. W. 
Published: May 2005

AbstractPrevious studies have identified a group of cells in the dorsolateral hypothalamus that project to many different areas in the CNS, such as thalamus, diagonal band of Broca, basal ganglia, cerebral cortex, hippocampus, and olfactory bulb. Their role is presently unknown, but the cells have been reported to stain for an intriguing array of putative neurotransmitter‐related substances, including α‐melanocyte‐stimulating hormone (αMSH), melanin‐concentrating hormone (MCH), human growth‐hormone‐releasing factor 1–37 (hGRF 1–37), corticotropin‐releasing factor (CRF), metorphamide, and acetylcholine esterase. A monoclonal antibody produced in the present study, αCl1, stains both the cell bodies of this system in hypothalamus, with a punctate pattern, and varicose fibers in the various target areas. In double‐label immunocytochemical experiments in rat DLH, αCl1 and MCH staining exactly overlaps. Concentrations of αMSH and MCH high enough to completely block staining with the corresponding antisera had no effect on staining with αC11. Similarly, CRF, hGRF 1–37, and metorphamide were unable to block αCl1 staining. The results suggest that the antigenic epitope for αCl1 is not contained in αMSH, MCH, CRF, hGRF, or metorphamide, and thus, that αCl1 is detecting another antigen uniquely expressed in these neurons. The punctate appearance of staining in the hypothalamus and the concentration of staining in fiber varicosities suggests that the αCl1 epitope may be involved in synaptic function.
Bimodal regulation of protein phosphorylation by a ganglioside in mat brain membrane
Authors: Nakaoka T. , Tsuji S. , Nagai Y. 
Published: May 2005

AbstractWhether or not a ganglioside influences the protein phosphorylation in the rat brain membrane fraction was investigated. Phosphorylation of the 72 kDa protein was significantly affected by the addition of 80 nM GQlb in vitro, which is far below the reported concentration of gangliosides that affects protein phosphorylation in the neuronal membrane fraction. This action of GQlb was bimodal: it being not only stimulatory as to the incorporation of phosphate into the 72 kDa protein on incubation for 20 sec, but also as to the release of phosphate from or breakdown of the 72 kDa protein on incubation for more than 5 min. Eighty nM GQlb did not noticeably affect ATPase in the same fraction. These results suggest that the transphosphorylation of the 72 kDa protein is affected by the interaction of GQlb with either the responsible enzymes or the 72 kDa protein as a substrate.
Establishment and characterization of a mouse Schwann cell line which produces myelin in vivo
Authors: Boutry J.‐M. , Hauw J.‐J. , Gansmüller A. , Di‐Bert N. , Pouchelet M. , Baron‐Van Evercooren A. 
Published: May 2005

AbstractA Schwann cell line (MSC 80) was established from purified mouse Schwann cell cultures using large doses of serum. MSC 80 cell line is an aneuploid cell line which has a doubling time of 17 hr and has been maintained through more than 110 passages. Most of MSC 80 cells are of bipolar or stellate (3–5 processes) shape. A few others are irregular in shape, gigantic, and multinucleated. All MSC 80 cells express antigens of myelin‐forming Schwann cells such as S‐100, 224/58, laminin, and other glycoproteins of the extracellular matrix. However, they also express the nonmyelin‐forming Schwann cell antigen GFAP. By time‐lapse cinematography, MSC 80 cells exhibit the Schwann cell characteristic rhythmical undulations. When induced to form aggregates in agar, they form intercellular junctions and basement membrane‐like structures. In addition, after transplantation in or at a distance from a lysolecithin induced lesion, MSC 80 cells from myelin around the host demyelinated axons. MSC 80 cells thus express, when isolated in vitro, some of the normal myelin‐forming Schwann cell phenotype. In addition, they present the major advantage of forming myelin when associated with axons in vivo. © 1992 Wiley‐Liss, Inc.
Cloning of cDNAs encoding human S‐100 α and β subunits and their differential expression in human tumor cell lines
Authors: Morii K. , Tanaka R. , Takahashi Y. , Kuwano R. 
Published: May 2005

AbstractWe isolated nearly full‐length clones of S‐100 α and β subunit cDNAs from a human brain cDNA library. The α subunit cDNA was 579 bp long and contained 99 bp of 5′‐noncoding region, 282 bp of coding region, and 198 bp of 3′‐noncoding region. The β subunit cDNA was 743 bp long and contained 57 bp of 5′‐noncoding region, 276 bp of coding region, and 410 bp of 3′‐noncoding region. An amino acid sequence comparison between human and bovine α subunits and between human and rat β subunits showed that both subunits were nearly entirely conserved. The amino acid sequences of human α and β subunits were conserved at both Ca2+‐binding domains.Northern blot analysis of brain RNA showed that human α and β subunit cDNA probes discriminated between α and β subunit mRNAs. By using these subunit‐specific cDNA probes, it was demonstrated that α and β subunit mRNAs were expressed in different manners among tumor cell lines: β was detected in melanoma and some glioma cell lines, while α was detected only in a melanoma cell line. Southern blot analysis showed that there were no major deletions and rearrangements of α and β subunit genes in these cell lines, regardless of the level of α and β subunit expression, suggesting that the expression of these subunits may be regulated at the transcriptional or RNA stability level. © 1992 Wiley‐Liss, Inc.