bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive astrocytes are widespread in the cortical gray matter of amyotrophic lateral sclerosis
Authors: Nagy D. , Kato T. , Kushner P. D. 
Published: January 2005

AbstractThe distribution of reactive astrocytes was examined in the cortical gray matter of non‐motor and motor regions from cases of familial and sporadic amyotrophic lateral sclerosis (ALS) and compared to that of β‐amyloid deposits. By glial fibrillary acidic protein immunocytochemistry, patches of reactive astrocytes, characterized by multiple reactive astrocytes in a circular or patch‐like formation, occurred in 12 of 15 ALS cases examined. These patches of reactive astrocytes were not restricted to the motor cortex but were found in the gray matter in ALS in all examined brain regions, including frontal, temporal, inferior parietal, cingulate, occipital, and motor cortices, from both familial and sporadic ALS cases. Reactive astrocytes were also found in the subpial region and at the gray/white matter junction. Because patches of astrocytes can occur in association with senile plaques, β‐amyloid was localized. By immunostaining, β‐amyloid deposits were observed in five of the 15 ALS cases: three cases had only early plaques, two had both early and classic plaques. The number of ALS cases with both astrocyte patches and amyloid plaques was four of 15, but typically astrocyte patches in ALS occurred without any evidence of an association with β‐amyloid deposits. Therefore, the astrocyte patches in ALS are not the result of β‐amyloid deposition. The widespread occurrence of reactive astrocytes, as patches in the cortical gray matter and in the subpial region and at the gray/white matter junction, is evidence of a widespread pathology in ALS cortex in both familial and sporadic forms of the disease. © 1994 Wiley‐Liss, Inc.
Ubiquitin‐protein conjugates in different structures of the central nervous system of the rat
Authors: Adamo A. M. , Moreno M. Besio , Soto E. F. , Pasquini J. M. 
Published: January 2005

AbstractThe capacity to form ubiquitin (Ub)‐protein conjugates was investigated in the cytosol of different structures of the rat central nervous system (CNS) in order to confirm the presence of this extralysosomal, adenosine triphosphate (ATP)‐dependent, protein degradation system as well as its structural localization. Using 125I‐Ub, we found that in the presence of ATP, the cytosol obtained from whole brains was able to form high molecular weight Ub‐protein conjugates. These conjugates could be detected after sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and radioautography. The formation of these conjugates was much higher in the cerebral cortex than in the brain stem, which is mainly constituted by white matter, being intermediate in the cytosol isolated from whole brain total homogenates. These results suggested to us that under normal conditions the capacity to form Ub‐protein conjugates was mainly located in structures containing neuronal cell bodies. Strong support for this contention was obtained when the cytosol isolated from rat optic nerves or from oligodendroglial cells isolated from whole brain was found to be totally unable to form Ub‐protein conjugates. The inability of certain CNS structures to form conjugates with Ub could be attributed, among other reasons, to the lack of enzymes catalyzing the various steps of the Ub degradation system, to the absence of short half‐life (target) proteins in those structures, or to the lack of activity of the enzymes catalyzing the reaction due to regulatory control mechanisms operating under normal conditions. © 1994 Wiley‐Liss, Inc.
VASE exon expression alters NCAM‐mediated cell‐cell interactions
Authors: Chen A. , Haines S. , Maxson K. , Akeson R. A. 
Published: January 2005

AbstractThe neural cell adhesion molecule (NCAM) is found on cells as several related polypeptides formed by alternative splicing of the single NCAM gene. The alternatively spliced 30‐bp VASE exon in the fourth immunoglobulin‐like domain is the structural variation nearest those portions of the polypeptide proposed to mediate cell‐cell adhesion. To test the ability of distinct forms of the NCAM molecules to mediate cell adhesion, L cells were transfected with expression vectors encoding rat 140 kD NCAM ± the VASE exon. L cell lines which expressed these polypeptides were isolated and tested for self‐aggregation in a low shear, rapid aggregation assay. Increased cellular aggregation of the transfectants was observed to be a function of the NCAM molecule expressed. These transfected cells showed segregation in a long term co‐aggregation assay: cells expressing NCAM — VASE formed aggregates which tended to exclude cells expressing NCAM + VASE and vice versa. These results provide direct evidence that this small difference in NCAM structure is sufficient to allow segregation of cells. © 1994 Wiley‐Liss, Inc.
Human neurocytoma cells in culture show characteristics of astroglial differentiation
Authors: Westphal M. , Stavrou D. , Nausch H. , Valdueza J. M. , Herrmann H.‐D. 
Published: January 2005

AbstractCultured human neurocytoma cells from two neurosurgical patients were analysed for their immunocytochemical staining patterns and growth characteristics. In both cases, the cells stained positive for glial acidic fibrillary protein (GFAP) within one day of tissue culture in medium, with and without fetal calf serum, whereas the histological tumor specimens were negative. Both cases contained cells concomitantly expressing GFAP and synaptophysin (SNP) in the primary cultures. Epidermal growth factor (EGF) was mitogenic for the cultured cells but not platelet derived growth factor alpha (PDGF AA) or nerve growth factor (NGF). It is concluded that the human neurocytomas may represent neoplasms of a pluripotent neuroglial cell which can provide an interesting model to study the determinants for human glial/neuronal differentiation in vitro. © 1994 Wiley‐Liss, Inc.
Long‐term effects of deprivation of cell support in the distal stump on peripheral nerve regeneration
Authors: Bajrović F. , Bresjanac M. , Sketelj J. 
Published: January 2005

AbstractThe distal stump of an injured peripheral nerve supports regenerating axons by offering a favourable growth substratum and several cell‐produced growth factors. Deprivation of cellular factors alone has been shown not to prevent fairly rapid axonal elongation after nerve injury if the growth substratum was preserved. The present study examined possible long‐term untoward effects of cell support deprivation during an early phase of nerve regeneration. Rat sciatic nerve was crushed and a 25 mm long distal nerve segment was made acellular by freezing‐thawing, while the integrity of the growth substratum for the regenerating axons was preserved. Toe‐spreading reflex and skin sensitivity to pinch in the foot were monitored to follow recovery of motor and sensory function, respectively. The number of myelinated axons was determined in the sciatic nerve proximally to the lesion site, and distally in the predominantly sensory sural nerve as well as in the mixed motor nerve to the soleus muscle. Except for a short delay in the onset of recovery, explainable by the reduced elongation rate of axons growing through the acellular nerve segment, we found no deleterious effect of cell support deprivation on sensory or motor function recovery after nerve crush. Most of regenerating sensory neurons did not critically depend on the distal stump cell support. However, a 15% and 25% loss of myelinated axons both proximally to the lesion and distally in the sensory sural nerve, respectively, indicated that a corresponding minor loss of injured sensory neurons occurred when they were deprived of such cell support even if provided with a favorable growth substratum for successful regeneration. In these animals, Dexamethasone application in a dose shown to reduce nerve growth factor (NGF) production in the proximal nerve segment did not detectably affect nerve regeneration. Under the same conditions of cell support deprivation, however, no axon loss could be demonstrated in the nerve to the soleus muscle, suggesting that the regenerating proprioceptive sensory neurons are less dependent on the distal stump cell support than the cutaneous ones. Copyright © 1994 Wiley‐Liss, Inc.
Fever and feeding in the rat: Actions of intrahypothalamic interleukin‐6 compared to macrophage inflammatory protein‐1β (MIP‐1β)
Authors: Myers R. D. , Lopez‐Valpuesta F. J. , Minñano F. J. , Wooten M. H. , Barwick V. S. , Wolpe S. D. 
Published: January 2005

AbstractThe chemokines, macrophage inflammatory protein‐1 (MIP‐1) and its subunit MIP‐1β, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre‐optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (Tb) of MIP‐1β with that of interleukin‐6 (IL‐6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro‐injections, radio transmitters which monitor Tb continuously were inserted intraperitoneally in each of 15 male Sprague‐Dawley rats. Each micro‐injection was made in a site in the AH/POA in a volume of 1.0 μl of pyrogen‐free artificial CSF, recombinant murine MIP‐1β, or recombinant human IL‐6. MIP‐1β in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in Tb of 2.4 ± 0.21°C reached by 3.7 ± 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL‐6 induced a dose dependent fever of similar latency and a mean maximal increase in Tb of 1.2 ± 0.25°C, 1.8 ± 0.15°C, and 2.1 ± 0.22°C and duration of 6.2 ± 1.28 hr, 6.7 ± 0.49 hr, and 6.8 ± 0.65 hr when given in doses of 25, 50, and 100 ng, respectively. These results show that MIP‐1β and the highest dose of IL‐6 induce a fever of comparable intensity, but MIP‐1β exerts its action in a much lower concentration. Thus, the de novo synthesis and subsequent action of the MIP‐1 family of cytokines on neurons of the AH/POA in response to a pyrogen challenge apparently play a functional role in the pathogenesis of fever. Further, the endogenous activity of IL‐6 in the hypothalamus which is enhanced in response to a lipopolysaccharide also may reflect its essential part in the acute phase response to a bacterial challenge. Copyright © 1994 Wiley‐Liss, Inc.
Expression of the putative pheromone and odorant transporter vomeromodulin mRNA and protein in nasal chemosensory mucosae
Authors: Krishna N. S. Rama , Getchell M. L. , Getchell T. V. 
Published: January 2005

AbstractIn nasal chemosensory systems, glandular proteins associated with the vomeronasal and olfactory epithelia perform specific perireceptor functions associated with sensory transduction. Vomeromodulin, a recently identified glycoprotein synthesized by the lateral nasal glands, is proposed to be a pheromone transporter (Khew‐Goodall et al., FASEB J 5:2976–2982, 1991). In our study, we have investigated its expression in vomeronasal, olfactory, and respiratory nasal mucosae of rats and humans using in situ hybridization and immunocytochemical techniques. In the rat, vomeromodulin mRNA and protein were localized abundantly in the glandular acini of the maxillary sinus component of the lateral nasal glands. In addition, the vomeronasal and posterior glands of the nasal septum also expressed vomeromodulin mRNA and protein. Vomeromodulin immunoreactivity was localized extracellularly in the mucus of the sensory and non‐sensory epithelia of the vomeronasal organ, and in the mucociliary complex of the olfactory, respiratory, and associated nasal epithelia. In human nasal mucosae, vomeromodulin immunoreactivity was localized in the mucociliary complex of the vomeronasal and respiratory epithelia. Comparison of the localization of vomeromodulin with that of odorantbinding protein, which is also synthesized in the lateral nasal glands of rats, revealed that odorant‐binding protein was expressed in a completely separate glandular region, namely the ventral component. In the septal glands, vomeromodulin was expressed in the posterior glands whereas odorant‐binding protein was localized in the anterior glands. Odorant‐binding protein immunoreactivity was not observed in the vomeronasal glands. In contrast, both proteins were localized in the mucus of vomeronasal, olfactory, and respiratory epithelia. Our results suggest that vomeromodulin, like odorant‐binding protein, functions as a chemosensory stimulus transporter associated with perireceptor processes in vomeronasal and olfactory transduction. Copyright © 1994 Wiley‐Liss, Inc.
Astroglia‐released factor shows similar effects as benzodiazepine inverse agonists
Authors: Rigo J.‐M. , Belachew S. , Lefebvre P. P. , Leprince P. , Malgrange B. , Rogister B. , Kettenmann H. , Moonen G. 
Published: January 2005

AbstractMedia conditioned by cultured neonatal cerebral cortex microexplants (CCM) or astrocytes (ACM) contain low molecular weight (<1,000 Da) substance(s) which inhibits the gamma aminobutyric acid (GABA)‐induced inward current recorded in cerebellar granule cells and hippocampal neurons in culture using the whole‐cell patch‐clamp technique. This effect is specific for CCm and ACM, as medium conditioned by PC12 cells (PC12CM) does not affect the GABA response of these cells. It is also specific for GABA‐induced currents because glutamate‐induced currents do not change either in amplitude or in shape in the presence of CCM or ACM. The inhibitory effect on the GABA response in cerebellar granule cells of both ACM and CCM could be suppressed by flumazenil, a specific benzodiazepine (BZD) antagnoist and could be mimicked by two BZD inverse agonists. These data thus demonstrate the presence of a BZD inverse agonist‐like activity in CCM and ACM. This effect of ACM on different neuronal cell types was heterogenous since no detectable effect could be observed on the GABA‐induced current in GABA‐responsive dorsal root ganglion (DRG) neurons, presumably reflecting a functional heterogeneity of the GABAA receptors present in these different neuronal subsets. By the release of such an endogenous BZD inverse agonist like activity, glia cells could possibly modulate GABAA receptor‐mediated responses. © 1994 Wiley‐Liss, Inc.
β/A4‐evoked degeneration of differentiated SH‐SY5Y human neuroblastoma cells
Authors: Lambert M. P. , Stevens G. , Sabo S. , Barber K. , Wang G. , Wade W. , Krafft G. , Snyder S. , Holzman T. F. , Klein W. L. 
Published: January 2005

Abstractß/A4 peptides are known to induce neurodegeneration in cultures of rat brain cells and rat neural cell lines (Yankner et al: Science 250:279–282, 1990; Behl et al: Biochem Biophys Res Commun 186:944–950, 1992). The current data show that these peptides induce similar neurodegeneration in SH‐SY5Y neuroblastoma cells, extending characterization of ß/A4 toxicity to a human nerve cell line. Human SH‐SY5Y cells respond to aggregated ß/A4 with changes in cell shape, membrane blebbing, antigenic modification, loss of attachment to the substrate, and cell death. ß/A4 peptides require aggregation for maximum toxic effects, as cellular degeneration is evoked by aggregated ß/A4 1‐42 and 4‐41 cysteine but not by monomeric ß/A4 1‐40. Aged (pre‐aggregated) ß/A4 1‐40 also evoked neurodegeneration. Antigenic changes comprise upregulation of Alzheimer's‐type tau epitopes, recognized by the PHF‐1 and Alz‐50 monoclonals. These particular changes in tau support the connectivity between this in vitro model and mechanisms leading to neurodegeneration in Alzheimer's disease. A significant feature of the SH‐SY5Y response is that cells must be differentiated before they become sensitive to the degeneration evoked by ß/A4. Signaling pathways leading to ß/A4‐evoked neurodegeneration thus are under experimental control, becoming complete only when proliferating cells withdraw from the cell cycle and develop a postmitotic phenotype. © 1994 Wiley‐Liss, Inc.
ω‐Contoxin binding sites and regulation of transmitter release in cerebellar granule neurons
Authors: Elster L. , Saederup E. , Schousboe A. , Squires R. F. 
Published: January 2005

AbstractThe protective action of Ca2+ and a series of other divalent cations on heat inactivation (48°C, 30 min) of [125I]ω‐conotoxin (CTX) binding sites was investigated in membranes prepared from rat forebrain. Moreover, the influence of GABA (500 ω) on this protection was studied. Binding of [125I]CTX as well as its inhibitory action on K+ (55 mM) stimulated, Ca2+‐dependent transmitter release were studied in rat cerebellar granule neurons cultured in the presence or absence of the GABAA receptor agonist THIP (4,5,6,7‐tetratydroisoxazolo[5,4‐c]pyridin‐3‐ol). In cells cultured in the presence of THIP (150 ω) it was investigated whether the ability of THIP to inhibit evoked transmitter release could be influenced by CTX. Ca2+ and other divalent cations could effectively protect against heat inactivation of [125I]CTX binding sites in rat forebrain membranes, but this protective action was not influenced by the presence of 500 ω GABA. The cultured cerebellar granule neurons exhibited specific binding sites for [125I] CTX, the number of which was independent of exposure of the cells to THIP during the culture period. Evoked transmitter release was inhibited by CTX with an IC50 value of 13 nM. In neurons cultured in the presence of 150 ω THIP, THIP could dose‐dependently inhibit evoked transmitter release, but this inhibitory action was not influenced by CTX (20 nM). The results show that cerebellar granule neurons exhibit functionally meaningful CTX binding sites. An association between such sites and GABA receptors is not apparent. © 1994 Wiley‐Liss, Inc.
Mitogenic effects of platelet‐derived growth factor, fibroblast growth factor, transforming growth factor‐β, and heparin‐binding serum factor for adult mouse Schwann cells
Authors: Watabe K. , Fukuda T. , Tanaka J. , Toyohara K. , Sakai O. 
Published: January 2005

AbstractMitogenic effects of fetal calf serum (FCS), platelet‐derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor‐β (TGF‐β), and forskolin to adult mouse Schwann cells were examined by bromodeoxyuridine (BrdU) incorporation and double immunofluorescence for S100 and BrdU. PDGF‐BB, basic FGF, and TGF‐β1 and β2 were all mitogenic for Schwann cells in media containing FCS. Forskolin suppressed the mitogenic activity of these factors. In serum‐free media, PDGF‐BB and bFGF were also mitogenic, but TGF‐β1 and β2 were not. Heparin‐binding fractions of FCS obtained by heparin‐Sepharose chromatography synergized with TGF‐β1 and β2 to produce a mitogenic response. Since PDGF‐BB, acidic FGF, and basic FGF were not detected in these fractions by immunoabsorption and immunoblot assays, the presence of unidentified heparin‐binding molecules in FCS bioactive for adult mouse Schwann cells is suggested. © 1994 Wiley‐Liss, Inc.
Induction of low‐affinity GABAA receptors by the GABA‐agonist THIP (4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol) in cultured rat cerebellar granule cells is prevented by inhibition of polyamine sbiosynthesis
Authors: Abraham J. H. , Seiler N. , Schousboe A. 
Published: January 2005

AbstractGABAA agonist‐induced formation of low‐affinity GABAA receptors in cultured cerebellar granule cells was studied in the presence or absence of α‐difluoromethylornithine (DFMO), a blocker of polyamine formation. High‐ and low‐affinity GABAA receptors were monitored by Scatchard analysis of [3H]GABA binding to membranes from cells cultured for either 4 or 10 days in the presence or absence of the GABA agonist 4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol (THIP). Cultures grown for 4 days were exposed to THIP and DFMO for an additional period of 6 hr (acute exposure), whereas cultures grown for 10 days were exposed to the same agents during the entire culture period (chronic exposure). Regardless of the culture period or drug exposure protocol, control cells expressed only a high‐affinity (KD 7 nM) binding site for GABA, whereas the cultures treated with THIP for either 6 hr or 10 days exhibited an additional low‐affinity binding site (KD ∼ 500 nM). Chronic exposure to DFMO prevented the THIP induction of low‐affinity GABAA receptors, whereas acute exposure to DFMO had no effect on the ability of THIP to induce low‐affinity GABAA receptors. Measurements of the intracellular polyamine concentration demonstrated a slight decrease in the putrescine level in the granule cells exposed to DFMO or THIP + DFMO for 6 hr. In contrast, granule cells chronically (10 days) exposed to DFMO or THIP + DFMO were depleted of putrescine and spermidine. Hence, the ability of THIP to induce low‐affinity GABAA receptors was prevented by the simultaneous depletion of the cellular content of putrescine and spermidine, whereas inhibition of ornithine decarboxylase and of putrescine formation was not sufficient to prevent THIP‐induced receptor formation. © 1994 Wiley‐Liss, Inc.
Acute tolerance to the excitatory effects of opioids in the rat hippocampus
Authors: Angelopoulos E. , Koutsoukos E. , Maillis A. , Zioudrou C. , Stefanis C. 
Published: January 2005

AbstractProlonged iontophoretic administrations of δ‐ and μ‐selective opioid receptor agonists were conducted in the hippocampus of rats, in order to study the possible development of acute tolerance to the excitatory effects of the opioids. Acute tolerance (AT) to the excitatory effects of the 8‐selective opioid receptor agonist Tyr‐D‐Ser‐Gly‐Phe‐Leu‐Thr (DSLET) was observed when the drug was applied locally for 3–5 min in the CA1 hippocampal pyramidal neurons. The acute tolerance was expressed as a decrease in the commissurally evoked spike responsiveness during peptide's administration and led to a long‐lasting potentiation of the population spike (PS) upon its withdrawal. In all cases, where AT and spike potentiation were evident, the population excitatory postsynaptic potential (pEPSP) remained unaltered. Pharmacological studies of AT and long‐lasting spike potentiation showed the following: (1) the non‐selective opioid receptor antagonist, naloxone, while effective in blocking the excitatory effects of DSLET when applied prior and during the application of the latter, failed to exhibit and effect on the long‐lasting potentiating effect of the opioid; and (2) during the spike potentiation phase, administration of DSLET exhibited a depressant effect towards baseline values. This depressant effect of the opioid was evident 2–3 min from the beginning of the application and was completely antagonized by naloxone. The above results show that the development of acute tolerance to the excitatory effects of the DSLET led to long‐lasting spike potentiation, which manifests a withdrawal phenomenon. © 1995 Wiley‐Liss, Inc.
Insulin‐like growth factors protect against diabetic neuropathy: Effects on sensory nerve regeneration in rats
Authors: Ishii Douglas N. , Lupien S. B. 
Published: January 2005

AbstractNeuropathy is an enigmatic and debilitating complication of diabetes. A consensus as to the pathogenesis of this disorder has yet to emerge. Recently, it has been found that the insulin‐like growth factors (IGFs) regulate peripheral nerve regeneration, and IGF content is reduced in various diabetic tissues. We tested herein the hypothesis that IGF administration can prevent or ameliorate the impairment of sensory nerve regeneration in streptozotocin diabetic rats. Miniosmotic pumps released small local doses of IGF‐I from a catheter routed near a site of sciatic nerve crush or larger systemic doses of IGF‐I or IGF‐II from a distant subcutaneous site. Whether administered locally or systemically, IGFs protected against the impairment of sensory nerve regeneration. Surprisingly, this protection was obtained despite unabated hyperglycemia. Therefore, the neuropathy involving sensory nerve regeneration in diabetes can be ameliorated or prevented by IGF treatment, independently of hyperglycemia. © 1995 Wiley‐Liss, Inc.