bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon γ, interleukin 4 and transforming growth factor β in experimental autoimmune encephalomyelitis in lewis rats: Dynamics of cellular mrna expression in the central nervous system and lymphoid cells
Authors: Issazadeh S. , Mustafa M. , Ljungdahl Å. , Höjeberg B. , Dagerlind Å. , Elde R. , Olsson Tomas 
Published: January 2005

AbstractThe potential role of certain important immunoregulatory and effector cytokines in autoimmune neuroinflammation have been studied. We have examined the expression of mRNA, with in situ hybridization, of interferon ‐γ (IFN‐γ), interleukin 4 (IL‐4) and transforming growth factor β (TGF‐β) both in sections of spinal cords and the antigen‐induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63–88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats.In spinal cords, the target organ in EAE, cells expressing mRNA for IFN‐γ, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.), and then gradually decreased concomitant with recovery. Very few IL‐4 mRNA‐expressing cells appeared in the spinal cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF‐β did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN‐γ, while TGF‐β may act to limit central nervous system (CNS) inflammation.In lymphoid organs, primed MBP 63–88 reactive T cells showed an interesting time‐dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63–88‐induced production of both IFN‐γ and IL‐4. Such cells may act in the initiation and promotion of the disease. Later, in the recovery phase, MBP 63–88 induced lymphoid cells to TGF‐β production. Thus, an autoantigen‐specific production of TGF‐β occurred during EAE and hypothetically such a mechanism may serve to downregulate aggressive autoimmunity systemically. © 1995 Wiley‐Liss, Inc.
Kainic acid‐induced seizures and brain damage in the rat: Role of calcium homeostasis
Authors: Berg M. , Bruhn T. , Frandsen Aa. , Schousboe A. , Diemer N. H. 
Published: January 2005

AbstractSeizure activity induced by kainic acid (KA) and subsequent neuronal death are thought to be associated with an increase in cytoplasmic free calcium ([Ca2+]i) and can be prevented by N‐methyl‐D‐aspartate (NMDA) antagonists. In addition to influx through receptor operated Ca2+ channels the increase in [Ca2+]i may be the result of an increased influx through voltage‐operated calcium channels and/or release from intracellular deposits. It was therefore investigated whether compounds other than NMDA antagonists with known actions on the intracellular Ca2+ homeostasis had any protective effect against KA‐induced neuronal death. Voltage‐operated calcium channels in the cell membrane were blocked with the L‐type ion channel antagonist, Nimodipine (1.0 mg/kg), and release of Ca2+ from internal stores was prevented with Dantrolene (10 mg/kg). Animals from two control groups injected with kainate (8 mg/kg) exhibited a survival rate of 67 and 53%, respectively. Countings of neurons in dorsal hippocampus showed subtotal or total loss in the CA1 and CA3 subregions. There were no significant differences concerning seizure and survival rates in the groups injected with kainate and treated with Dantrolene or Nimodipine and the control groups. The group treated with Dantrolene showed no neuropathological changes in the hippocampal CA3 region and only slight changes in the CA1 region, while the neuron loss in the Nimodipine group did not differ from that of its control group. The results emphasize the importance of Dantrolene‐sensitive Ca2+ release from intracellular stores for the development of seizureinduced neuronal death. © 1995 Wiley‐Liss, Inc.
N‐methyl‐D‐aspartate‐evoked release of cyclo‐oxygenase products in rabbit hippocampus: An in vivo microdialysis study
Authors: Łazarewicz J. W. , Salińska E. 
Published: January 2005

AbstractIn vivo microdialysis of the rabbit hippocampus was used to study the effects of N‐methyl‐D‐aspartate (NMDA) receptor stimulation on dialysate concentrations of thromboxane B2 (Tx B2)‐ and 6‐keto prostaglandin F1α (6‐keto PGF1α)‐immunoreactive materials that are stable metabolites of biologically active thromboxane A2 and prostacyclin. All pharmacological substances were applied in the dialysis medium. The application of 1 mM NMDA for 20 min resulted in five‐ and eightfold increases in Tx B2 and 6‐keto PGF1α concentrations, respectively. An increase in NMDA concentration to 2.5 mM did not potentiate a peak eicosanoid release, but significantly prolonged this effect. Either 10μM MK‐801 or the extrusion of Ca2+ from the dialysis medium inhibited the release by about 50%. Quinacrine, a phospholipase A2 inhibitor (250 μM), decreased the NMDA‐evoked eicosanoid release by 30%, whereas 10μM indomethacin, a cyclo‐oxygenase inhibitor, completely suppressed the release. One hundred micromolar furegrelate, an inhibitor of thromboxane synthase, reduced by 75% Tx B2 release with concomitant 100% increase in 6‐keto PGFμ formation. Thus, stimulation of NMDA receptors induces calcium‐dependent formation of thromboxane A2 and prostacyclin in the hippocampus, which may have pathophysiological implications. The neuronal site of their formation seems probable, although a transcellular mechanism of their synthesis should be also considered. © 1995 Wiley‐Liss, Inc.
Biosynthesis and regulation of expression of the HNK‐1 epitope on myelin‐associated glycoprotein in a transfected cell model system
Authors: Pedraza L. , Spagnol G. , Latov N. , Salzer James L. 
Published: January 2005

AbstractThe HNK‐1 antibody recognizes a carbohydrate epitope expressed by many cell adhesion molecules in the nervous system that has been proposed to be an important adhesive determinant. This epitope is particularly prominent on the myelin‐associated glycoprotein (MAG) and is related to the antigenic target in an autoimmune mediated demyelinating neuropathy. Elucidation of the mechanisms underlying the biosynthesis and regulation of expression of the HNK‐1 epitope is therefore likely to have important functional and clinical implications. In order to investigate its biosynthesis and the regulation of its expression, we have expressed both human and rat MAG in several different cell lines by retroviral infection. These studies indicate that the cellular milieu determines whether the HNK‐1 epitope is expressed on the MAG polypeptide and provide an explanation for the significant variation in HNK‐1 levels that has been noted in different species. Using a transfected human neuroblastoma line, we have determined that this epitope is present on the fourth and/or fifth immunoglobulin‐like domain of rat MAG and that it is added intracellularly, probably in the trans Golgi. Finally we have found that expression of the HNK‐1 epitope is increased by activation of different second messenger systems, providing direct evidence that its expression can be regulated independently from that of the MAG polypeptide.© 1995 Wiley‐Liss, Inc.
Cyclic adenosine‐3′,5′‐monophosphate potentiates the synaptic potential mediated by NMDA receptors in the amygdala
Authors: Huang C. C. , Gean P. W. 
Published: January 2005

AbstractAn in vitro slice preparation of rat amygdala was used to study the actions of forskolin and cyclic adenosine‐3′,5′‐monophosphate (cAMP) analogues on the N‐methyl‐D‐aspartate (NMDA) receptor‐mediated synaptic potential (EPSPNMDA). Intracellular recordings were made from basolateral amygdala neurons in the presence of 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 10μM) and picrotoxin (50 μM) to pharmacologically isolate the EPSPNMDA. Application of forskolin (25 μM) markedly and persistently potentiated the EPSPNMDA In contrast, the inactive forskolin analogue, 1,9‐dideoxy‐forskolin, failed to affect the EPSPNMDA significantly. Superfusion of dibutyryl‐cAMP (dbcAMP, 200 μM) for 15 min caused a transient depression of the amplitude of EPSPNMDA. The EPSPNMDA amplitude was reduced to 68 ± 3% of control (n = 10) 15 min after the application, restored to its control value within 25 min, and followed by a long‐term potentiation (LTP). Pretreating the slices with 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, 5 μM), a selective A1 receptor antagonist, blocked the transient depressive phase produced by dbcAMP. This result suggests that the transient depression induced by dbcAMP was likely due to the interaction of dbcAMP or its breakdown products with adenosine A1 receptors.To determine the site of action, we examined the effect of forskolin on the postsynaptic responses to exogenously applied NMDA. Forskolin potentiated the postsynaptic depolarization induced by NMDA, suggesting that the enhancement is mediated, at least in part, by a persistent upregulation of postsynaptic NMDA receptor‐operated conductances.Occlusion experiments were performed to examine whether the sustained enhancements of EPSPNMDA produced by tetanic stimulation (TS) and forskolin share a common mechanism. Three episodes of TS were delivered to saturate the LTP and, under this condition, forskolin still caused a further potentiation of the EPSPNMDA. Similarly, TS, delivered after the EPSPNMDA was enhanced by forskolin or dbcAMP, produced LTP. These results suggest that the long‐term enhancements of EPSPNMDA produced by TS and forskolin are different and thus do not support the hypothesis that activation of protein kinase A triggers LTP. © 1995 Wiley‐Liss, Inc.
Purification and characterization of a low molecular weight endogenous glutamate binding inhibitor (LGBI) in porcine brain
Authors: Lee Y.‐H. , Bhattacharyya A. , Tang X. Wen , Seah E.‐C. , Schmidt K. , Deupree D. L. , Wu Jang‐Yen 
Published: January 2005

AbstractOne of the endogenous substances which modulate glutamate receptor binding was isolated and highly purified from porcine brain. The purification involved extraction of brain tissue with doubled distilled water, followed by gel filtration, anion exchange, cation exchange, and several steps of C18 reverse‐phase high performance liquid chromatography (HPLC). A low molecular weight glutamate binding inhibitor (LGBI) was purified to apparent homogeneity as judged from the elution profile of an HPLC column, in which a symmetrical peak was obtained when the eluate was monitored at 220 nm. The LGBI appears to be a small molecule (< 2 kD) that is heat‐and acid/base‐stable. The highly purified LGBI has no effect on GABAA and benzodiazepine receptor binding. The LGBI is not L‐glutamate, L‐aspartate or other negatively charged endogenous substances, since they are clearly separated from the LGBI in anion exchange chromatography. The inhibitory effect of the LGBI on [3H]L‐glutamate binding is reversible, and it only changes the Bmax while the Kd remains the same. Since the membrane preparations used for [3H]L‐glutamate binding assays for the detection of LGBI activity were enriched with quisqualate (QA)‐sensitive subtypes, it was suggested that the LGBI could be a modulator of the QA receptor. Some amino acids which produce significant inhibition of glutamate binding activity were also compared with the LGBI, and they all showed no resemblance to the LGBI. The chemical structure of the LGBI remains to be determined. © 1995 Wiley‐Liss, Inc.
Orphan receptor COUP‐TF I antagonizes retinoic acid‐induced neuronal differentiation
Authors: Neuman K. , Soosaar A. , Nornes H. O. , Neuman Toomas 
Published: January 2005

AbstractChicken ovalbumin upstream promoter‐transcription factors (COUP‐TF) are expressed in the developing nervous system and interact with nuclear hormone receptors to regulate expression of different genes. The role of COUP‐TF orphan receptors in neurogenesis is virtually unknown. To study the possible function of COUP‐TF I during neuronal differentiation, we generated COUP‐TF I overexpressing teratocarcinoma PCC7 cell lines and analyzed retinoic acid (RA)‐induced neuronal differentiation of these cells. COUP‐TF I overexpression results in the blockade of morphological differentiation after induction to differentiate. COUP‐TF I represses expression of micro‐tubule‐associated protein 2 (MAP2) gene and delays induction of growth‐associated protein 43 (GAP43) gene expression. In contrast, expression of the neurofilament light subunit (NF‐L) gene is not affected by COUP‐TF I overexpression during neuronal differentiation. Also, cells overexpressing COUP‐TF I do not stop proliferating after RA and dBcAMP treatment and possess suppressed transcriptional activation from different RA response elements. These results suggest that COUP‐TF I plays an important role in regulating RA‐induced neuronal differentiation.© 1995 Wiley‐Liss, Inc.
GABAB receptors increase intracellular calcium concentrations in chromaffin cells through two different pathways: Their role in catecholamine secretion
Authors: Parramón M. , González M. P. , Herrero M. T. , Oset‐Gasque M. J. 
Published: January 2005

AbstractThe activation of GABAB receptors of adrenal chomaffin cells produces an increase of [Ca2+]i measured by fura‐2 AM techniques. GABAB agonists 3‐aminopropylphosphinic acid or (‐)baclofen, at concentrations of 0.5 mM, increased basal Ca2+, values 332 ± 60.9 and 306 ± 40.5 nM, respectively, in cells suspended in a 2.5 mM Ca2+ buffer.The GABAB‐induced increase of [Ca2+]i seemed to have two different components. The first was due to an entry from the extracellular medium mainly through L‐type voltage‐dependent Ca2+ channels as the dihydropiridine nifedipine 50 μM was able to decrease it more than 60%, while ω‐conotoxin, which blocks N‐type channels, did not produce any change in the GABAB‐evoked Ca2+ increment. The second component was due to a release of Ca2+ from intracellular pools and was about one‐third of the total GABAB‐induced increase of [Ca2+]i. GABAB receptors stimulated inositol 1,4,5‐trisphosphate‐sensitive and not the caffeine‐sensitive Ca2+ store. In a low Ca2+ buffer after treatment with 2 μM angiotensin II, neither 0.5 mM 3‐APPA nor baclofen were able to produce an additional increase of [Ca2+]i, whereas 4 mM caffeine had no effect on GABAB response. This intracellular Ca2+ mobilization could be due to inositol 1,4,5‐trisphosphate accumulation produced by the activation of GABAB receptors. In fact, the specific agonists after 10 minutes incubation produced a dosedependent increase of inositol 1,4,5‐trisphosphate. The maximal effect was obtained at 100 μM baclofen and 3‐APPA, and it was 3.63 ± 0.75 and 3.2 ± 1.5 times the basal levels (7.3 ± 0.3 pmol/106 cells), respectively.In the absence of extracellular Ca2+, GABAB‐evoked catecholamine secretion and cyclic AMP formation were reduced more than 70%, suggesting an important role of extracellular Ca2+ in GABAB mechanisms in adrenal chromaffin cells. © 1995 Wiley‐Liss, Inc.
Hyperammonemia increases serotonin 1A receptor expression in both rat hippocampus and a transfected hippocampal cell line, HN2‐5
Authors: Alexander J. J. , Banerjee P. , Dawson G. , Tonsgard J. H. 
Published: January 2005

AbstractHyperammonemia is an important cause of cerebral dysfunction in liver failure. We used two well‐established models to induce hyperammonemia in rats, injection of urease and injection of methionine sulfoximine (MSO). Urease gave a 10‐fold increase in blood ammonia while MSO, a glutamine synthetase inhibitor, gave a 4‐fold increase in blood ammonia with no increase in brain glutamine levels. We observed a 2‐fold increase in 5‐HT1A receptor (5‐HT1A‐R) expression ([3H] 8‐OH‐DPAT binding) in hippocampus, and little change elsewhere, including thalamus in both models, thus eliminating a role for increased glutamine in the receptor induction. In contrast, a 4 to 8‐fold increase in 5‐HT1A‐R mRNA was observed both in hippocampus and thalamus, suggesting some post‐transcriptional regulation. In the absence of glutamine, ammonium acetate treatment of a hippocampal cell line which had been engineered to stably express the 5‐HT1A‐R (HN2‐5) gave a 1.5‐fold increase in [3H] 8‐OH‐DPAT binding and a 4‐fold increase in the mRNA levels for the 5‐HT1A‐R. We conclude that the cell line HN2‐5 is a good model for studying some of the biochemical sequelae of hyperammonemia and that changes in brain function are not only at the metabolic level, as thought earlier, but can also occur at the transcriptional level. © 1995 Wiley‐Liss, Inc.
Chromatographic and immunochemical characterization of rat brain neuropeptide Y‐like immunoreactivity (NPY‐LI) following repeated electroconvulsive, stimuli
Authors: Stenfors Carina , Mathé A. A. , Theodorsson E. 
Published: January 2005

AbstractThe present work investigates the possible existence of molecular heterogeneity of endogenous neuropeptide Y (NPY) in the rat brain and, if existing, whether it is affected by repeated electroconvulsive stimuli (ECS). Different column chromatographic techniques (gel‐permeation chromatography, HPLC, ion‐pair reverse‐phase HPLC) were used combined with immunochemical methods based on antisera directed towards two different epitopes of NPY (antiserum N1, directed towards the midportion of NPY, and antiserum C1, directed towards the C‐terminal end of NPY). Following repeated ECS increased concentrations of NPY were seen in the occipital cortex and hippocampus (P<0.001) when analyzed by direct radioimmunoassays (RIA). Chromatographic characterization showed that the NPY mainly consisted of intact NPY (1‐36) and sulphoxidated form of NPY, no short C‐terminal homologues were found. This is of importance since it has been shown that NPY (1‐36) has different biological properties compared to C‐terminal homologues. © 1995 Wiley‐Liss, Inc.
Effect of bacterial wall lipopolysaccharide (LPS) on morphology, motility, and cytoskeletal organization of microglia in cultures
Authors: Abd‐El‐Basset E. , Fedoroff S. 
Published: January 2005

AbstractWe examined the effect of bacterial wall lipopolysaccharide (LPS), a strong inflammatory agent, on the morphology, cell motility, cytoskeletal organization, and phagocytic activity of microglia in tissue cultures initiated from neopallia of newborn C3H/OuJ mice. Normally, the microglia in our cultures are non‐migratory and Mac‐1 positive, have ameboid cell morphology, no polarity, many short processes that extend into lamellipodia in opposing directions, and undulating cell membrane projections.When 1–5 μg/ml LPS is added to such cultures, some cells acquire polarity by forming a large lamellipodium and begin to migrate. Two hours later migration ceases; the membrane undulations stop; and the cells become non‐polar, assume a large, round, flat shape, and gradually develop many microspikes all over the cell body. Those cells that do not transform into large, round, flat cells enlarge and extend numerous lamellipodia in opposing directions.We found that the cytoskeleton of microglia is composed of actin, vimentin‐containing intermediate filaments (IF) and microtubules (MT). Vimentin‐containing IF and MT form dense networks that radiate into the cell periphery, whereas F‐actin is diffusely arranged throughout the cytoplasm. The LPS‐treated cells show changes in the organization of the main components of the cytoskeleton. F‐actin is reorganized by the formation of bundles‐ underneath and parallel to the cell membrane and other bundles projecting into the cores of the microspikes. The vimentin‐containing IF dense network reorganizes into two condensed rings, with fine strands of IF extended between the two rings and the MT networks become less dense and extend throughout the cytoplasm. The LPS treatment potentiates the phagocytic activity of the microglia. However, approximately 30% of microglia lose the expression of MHC class II antigens. © 1995 Wiley‐Liss, Inc.
Functional topography of myelin‐associated glycoprotein. II. Mapping of domains on molecular fragments
Authors: Meyer‐Franke A. , Tropak M. B. , Roder J. C. , Fischer P. , Beyreuther K. , Probstmeier R. , Schachner M. 
Published: January 2005

AbstractThe myelin‐associated glycoprotein (MAG), an adhesion molecule of the immunoglobulin (Ig) superfamily with five Ig‐like domains, was investigated with regard to its binding site(s) for the neuronal cell surface, collagen I, and heparin, using a panel of new monoclonal antibodies and cyanogen bromide cleavage fragments of MAG. All antibodies generated competed with each other for binding to MAG, indicating that they reacted with identical or closely related epitopes. Mapping of the reactive epitopes on recombinant deletion fragments of MAG expressed by Chinese hamster ovary (CHO) fibroblasts showed reactivity of monoclonal antibody 513 with domains I, II, and III, comprising the amino‐terminal end of the extracellular domain. Monoclonal antibody 15 recognized domain III only. Binding of MAG‐containing liposomes to neurons was blocked by antibodies 15 and 513. Cyanogen bromide (CNBr) fragments of domains I, II, and III bound to collagen type I under isotonic buffer conditions. CNBr fragments containing domains I and II were involved in binding to heparin. These observations suggest that domain III may be important for binding to the neuronal cell surface receptor for MAG, while domains I, II, and III interact with collagen type I and domains II and III with heparin. © 1995 Wiley‐Liss, Inc.
NGF‐producing transfected 3T3 cells: Behavioral and histological assessment of transplants in nigral lesioned rats
Authors: Westlund K. N. , Lu Y. , Kadekaro M. , Harmann P. , Terrell M. L. , Pizzo D. P. , Hulsebosch C. E. , Eisenberg H. M. , Perez‐Polo J. R. 
Published: January 2005

AbstractThe rodent fibroblast clonal cell line, 3T3, was retrovirally transfected with the rat nerve growth factor (NGF) gene and selected for NGF synthesis. This study tested the hypothesis that transplanted 3T3 cells, transfected to secrete nerve growth factor (3T3NGF+), change motor behavioral indices created by striatal denervation in a dose‐dependent fashion. 3T3NGF+ cells were transplanted into the lateral ventricle of rats following ipsilateral lesions of the substantia nigra pars compacta by stereotaxic injections of 6‐hydroxydopamine (10 μg), an established lesion model. Control groups included vehicle injections and transplanted untransfected cells. The extent of the lesions was measured by determining rotational behavior before and two weeks after transplantation. Immediately prior to transplantation, cells were incubated with the fluorescent dye marker, Dil. To assess cell viability, whole brains were cryosectioned and examined for Dil‐labeled 3T3 cells using fluorescent microscopy. The number Uf Dil‐labeled profiles in five animals per group were counted in at least five noncontiguous sections per animal. From these data a statistically derived estimate of viable, transplanted 3T3 cells was obtained. The number of surviving transplanted cells correlated with the behavioral changes measured. The 3T3NGF + transplants reduced rotational behavior, while control 3T3 transplants exacerbated rotational behavior. Thus, while NGF delivery was found to be beneficial, it was apparent that naive 3T3 had detrimental effects. These results underscore the importance of making doseresponse measurements when attempting transplantbased modifications of CNS behavior. © 1995 Wiley‐Liss, Inc.