bluuebunny/crossref_metadata_2025_split huggingface dataset:
GluR1 and GluR2/3 subunits of the AMPA‐type glutamate receptor are associated with particular types of neurone in laminae I–III of the spinal dorsal horn of the rat
Authors: Kerr R. C. Spike R. , Maxwell  , Todd  
Published: March 2003

AbstractGluR1 and GluR2 subunits of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor are expressed at high levels by neurones in laminae I–III of rat spinal dorsal horn, an area which contains numerous, densely packed small neurones. In order to determine whether these subunits are expressed by inhibitory or excitatory neurones, we combined pre‐embedding immunocytochemistry with antibodies that recognize either GluR1, or an epitope common to GluR2 and 3, with postembedding detection of γ‐aminobutyric acid (GABA) and glycine. Most (78%) of the neurones with GluR1‐immunoreactivity were GABA‐immunoreactive, and some of these were also glycine‐immunoreactive, whereas nearly all (97%) of the GluR2/3‐immunoreactive neurones were not GABA‐ or glycine‐immunoreactive.We carried out double‐immunofluorescence and confocal microscopy to provide further information on the neurochemistry of cells that express these subunits. As expected, all neurotensin‐ and virtually all somatostatin‐immunoreactive cells (which are thought to be excitatory interneurones) were GluR2/3‐ but not GluR1‐immunoreactive, whereas parvalbumin‐containing cells (most of which are GABAergic) possessed GluR1‐, but usually not GluR2/3‐immunoreactivity. Neurones that contained nitric oxide synthase (most of which are GABAergic) were more variable, with 57% GluR1‐immunoreactive and 41% GluR2/3‐immunoreactive. Cholinergic neurones in lamina III (which are also GABAergic) invariably showed each type of GluR‐immunoreactivity.These results suggest that neuronal populations in laminae I–III have characteristic patterns of GluR expression: GluR1 is particularly associated with inhibitory neurones, and GluR2 with excitatory neurones. This makes it likely that some of the AMPA receptors present on the inhibitory interneurones lack the GluR2 subunit, and may therefore have significant Ca2+‐permeability.
In vitro and in vivo behaviour of NDF‐expanded monkey Schwann cells
Authors: Avellana‐Adalid  , Bachelin  , Lachapelle  , Escriou  , Ratzkin  , Van Evercooren A. Baron‐ 
Published: March 2003

AbstractSchwann cells, the myelin‐forming cells of the peripheral nervous system may play a major role in the regeneration and remyelination not only of the peripheral but also of the central nervous system. The discovery of the mitogenicity of human recombinant forms of neuregulins (glial growth factors) on primate Schwann cells allows us to envisage a considerable expansion of these cells in culture with a view to autologous transplantation in the central nervous system. To assay this possibility, we used human recombinant neu‐differentiation factor beta (NDFβ) to expand monkey Schwann cells derived from perinatal and adult nerve biopsies. We report that NDFβ containing the epidermal growth factor (EGF)‐like domain (residues 177–228) is a potent mitogen for monkey Schwann cells but is more effective on perinatal than adult Schwann cells. Moreover, continuous treatment with NDFβ, does not seem to prevent Schwann cells differentiation into myelin‐forming cells after their transplantation into the demyelinated mouse spinal cord. These observations, in addition to the close similarities of in vitro behaviour which exist between human and monkey Schwann cells, indicate that monkey Schwann cells could be an ideal tool to study the potential and limits of autologous transplantation in a non‐human primate model of central nervous system demyelination.
VAMP‐1 and VAMP‐2 gene expression in rat spinal motoneurones: differential regulation after neuronal injury
Authors: Jacobsson Gunilla , Piehl Fredrik , Meister Björn 
Published: March 2003

AbstractVesicle‐associated membrane protein (VAMP; synaptobrevin) is involved in the molecular regulation of transmitter release at the presynaptic plasma membrane. VAMP exists in two isoforms, VAMP‐1 and VAMP‐2, which are transcribed from two separate genes and differentially expressed in the nervous system. In situ hybridization was used to examine whether VAMP isoform mRNA expression may be altered by experimental manipulations. The effect of nerve injury on VAMP‐1 and VAMP‐2 mRNA levels in motoneurones of the rat lumbar spinal cord was compared with lesion‐induced changes in the expression of choline acetyl transferase (ChAT) and α‐calcitonin gene‐related peptide (α‐CGRP) mRNA. After unilateral sciatic nerve transection (axotomy), VAMP‐1 mRNA expression decreased significantly in parallel with a downregulation of ChAT mRNA in axotomized motoneurones compared with the corresponding motoneurones on the contralateral unlesioned side. There was a rapid decrease in VAMP‐1 and ChAT mRNA levels at 2 days after axotomy, and at 7 days there was a 65% decrease in VAMP‐1 mRNA and a 48% decrease in ChAT mRNA. VAMP‐1 mRNA levels continued to decrease at 14 and 21 days, while ChAT mRNA levels had returned to normal at this time. In contrast, VAMP‐2 and α‐CGRP mRNA levels were upregulated in axotomized motoneurones. A significant increase for both VAMP‐2 and α‐CGRP mRNA levels was present 2 days after axotomy, and a maximum was reached after 7 days for α‐CGRP mRNA (163%) and after 14 days for VAMP‐2 mRNA (587%). Immunohistochemical analysis did not reveal any detectable changes in VAMP‐1‐ or VAMP‐2‐like immunoreactivity in the motoneurone cell soma after axotomy. In the proximal end of the transected sciatic nerve, there was an increase in VAMP‐1‐ and VAMP‐2‐LI, which was most prominent at 2 days after lesion. The results show that, in axotomized spinal motoneurones, VAMP‐1 mRNA is downregulated and VAMP‐2 mRNA is upregulated, indicating differential regulation of the two separate VAMP genes and differential roles for the two VAMP isoforms in the regulation of exocytosis after nerve injury.
Two types of calcium currents of the mouse bipolar cells recorded in the retinal slice preparation
Authors: De La Villa Pedro , Vaquero Cecilia F. , Kaneko Akimichi 
Published: March 2003

AbstractIn the vertebrate retina, the bipolar cell makes reciprocal synapses with amacrine cells at the axon terminal. It has been postulated that amacrine cells may control the transmitter release from bipolar cells by modulating their calcium currents (ICa). To clarify this possibility calcium currents were studied in bipolar cells of the mouse retina using a slice preparation. ICa was identified by voltage clamp protocols, ionic substitution and pharmacological tools.Depolarization to –30 mV from a holding voltage of –80 mV induced an inward current consisting of an initial transient and a long‐lasting sustained component. The transient component was inactivated by holding the membrane at more positive voltages. Addition of 100 μm nifedipine suppressed the sustained component, leaving the transient component almost intact. The sustained component was enhanced when external solution contained 0.1 μm Bay K 8644 or when the external Ca2+ was substituted by equimolar Ba2+. Omega‐conotoxin (10 μmω‐ctxn GVIA) did not alter either component. We concluded that the transient component is a low‐voltage activated T‐type ICa, while the sustained component is a high‐voltage activated L‐type ICa.T‐type ICa was recorded in all cells tested, while L‐type ICa was found only in cells that retained axon terminals ramifying in the inner plexiform layer. Thus, it is highly likely that L‐type ICa is generated at the axon terminal and contributes to the transmitter release from the bipolar cell.The present results confirm that in addition to the T‐type ICa that had been previously described, bipolar cells of the mammalian retina also contain L‐type ICa similar to the one that has been reported in bipolar cells of the goldfish. The use of retinal slice preparation allowed us to record this current that was not seen previously in the dissociated mouse bipolar cells.
VIP and PACAP potentiate the action of glutamate on BDNF expression in mouse cortical neurones
Authors: Pellegri Giovanni , Magistretti Pierre J. , Martin Jean‐Luc 
Published: March 2003

AbstractIn view of the neurotrophic effect of vasoactive intestinal peptide (VIP), the regulation of brain‐derived neurotrophic factor (BDNF) expression by VIP and the related peptide pituitary adenylate cyclase‐activating polypeptide (PACAP) was analysed by Northern blot in primary cultures of cortical neurones. Results reported in this article demonstrate that VIP and PACAP stimulate the expression of BDNF mRNA in primary cultures of cortical neurones and astrocytes. In primary cultures of cortical neurones, induction of BDNF mRNA by VIP and PACAP is completely inhibited by the N‐methyl‐d‐aspartate (NMDA) receptor antagonists MK‐801 and AP5, therefore indicating that VIP and PACAP do not stimulate BDNF expression directly but rather by potentiating the effect of glutamate tonically released by neurones and acting at NMDA receptors.In addition to its neurotrophic effects, BDNF has been shown to be involved in neuronal plasticity and results reported here suggest that by stimulating BDNF expression, VIP and PACAP could modulate synaptic plasticity in the cerebral cortex.
Pre‐ and postsynaptic blockade of neuromuscular transmission by Miller–Fisher syndrome IgG at mouse motor nerve terminals
Authors: Buchwald Brigitte , Weishaupt Andreas , Toyka Klaus Viktor , Dudel Josef 
Published: March 2003

AbstractMiller–Fisher syndrome, a variant of an acute inflammatory neuropathy is often associated with serum antibodies to the ganglioside GQ1b, but the pathogenic role of these antibodies and other serum factors is unclear. We here investigated the effect of highly purified immunoglobulin G (IgG) from patients with typical Miller–Fisher syndrome, recording quantal endplate currents by means of a perfused macro‐patch‐clamp electrode on hemidiaphragms of adult mice. The GQ1b‐positive and the GQ1b‐negative Miller–Fisher IgG as well as its monovalent Fab‐fragments depressed evoked quantal release in a fast and fully reversible, concentration and voltage dependent manner. The time‐course of quantal release was changed with the late releases becoming more frequent. The extent of depression of release followed a Michaelis–Menten kinetic and depended on the extracellular calcium concentration. In addition the amplitude of quanta was reduced postsynaptically. IgG and sera from healthy subjects had no effect. Our results indicate that in Miller–Fisher syndrome, IgG antibodies to an undetermined antigen depress the release process, most likely by interfering with the presynaptic Ca2+ inflow or by interacting with proteins of the exocytotic apparatus, and prevent the activation of postsynaptic channels. Antibodies thus seem to be one pathogenic factor for muscle weakness in Miller–Fisher syndrome and our findings may explain why muscle strength recovers rapidly after therapeutical plasmapheresis.
Long‐lasting enhanced expression in the rat hippocampus of NMDAR1 splice variants in a kainate model of epilepsy
Authors: Rafiki Amina , Ben‐Ari Yezekiel , Khrestchatisky Michel , Represa Alfonso 
Published: March 2003

AbstractChronic epilepsy is associated with increased excitability which may result from abnormal glutamatergic synaptic transmission involving altered properties of N‐methyl‐d‐aspartate (NMDA) receptors. To date two gene families encoding NMDA receptor subunits have been cloned, NR1 and NR2. Eight NR1 mRNAs are generated by alternative splicing of exons 5, 21 and 22; the NR1–1 to NR1–4 C‐terminal variants exist in the a or b version depending on the presence or absence of the domain encoded by exon 5. Epilepsy was induced in rats by unilateral intra‐amygdalar injection of kainate and animals were killed from 6 h to 4 months following the injection. Increased NR1 mRNA levels were observed during status epilepticus (6–24 h after the injection), both ipsilateral and contralateral, while a second wave of NMDAR1 mRNA increase occurred in chronic epileptic animals, between 21 days and 4 months following kainate injection. Our data show: (i) a permanent increase of the NR1–2a and NR1–2b mRNA species (containing exon 22) in all hippocampal fields, both ipsilateral and contralateral, and (ii) an increase of the NR1–3 (a and b) mRNAs (containing exon 21) in the ipsilateral CA1, and NR1–3a mRNA in the ipsilateral dentate gyrus. No long‐term changes were observed for the NR1–1 and NR1–4 splice variants. In the ipsilateral CA3 area a globally decreased mRNA expression was associated with neuronal loss. A possible contribution to the maintenance of the epileptic state by an increased expression of NMDA receptors is discussed.
Developmental regulation of T‐, N‐ and L‐type calcium currents in mouse embryonic sensory neurones
Authors: Desmadryl G. , Hilaire C. , Vigues S. , Diochot S. , Valmier J. 
Published: March 2003

AbstractWe investigated the development of a low (T‐type) and two high voltage‐activated (N‐ and L‐type) calcium channel currents in large diameter dorsal root ganglion neurones acutely isolated from embryonic mice using the whole‐cell patch‐clamp technique. The low and high voltage‐activated barium currents (LVA and HVA) were identified by their distinct threshold of activation and their sensitivity to pharmacological agents, dihydropyridines and ω‐conotoxin‐GVIA, at embryonic day 13 (E13), E15 and E17–18, respectively, before, during and after synaptogenesis. The amplitude and density of LVA currents, measured during a –40 mV pulse from a holding potential of –100 mV, increased significantly between E13 and E15, and remained constant between E15 and E17–18. The density of global HVA current, elicited by 0 mV pulse, increased between E13 and E15/E17–18.The density of the N‐type current studied by the application of ω‐conotoxin‐GVIA (1 μm) increased significantly between E13 and E15/E17–18. The use of the dihydropyridine nitrendipine (1 μm) revealed that the density of L‐type current remained constant at each stage of development. Nevertheless, application of dihydropyridine Bay K 8644 (3 μm) demonstrated a significant slowing of the deactivation tail current between embryonic days 13 and 15, which may reflect a qualitative maturation of this class of calcium channel current.The temporal relationship between the changes in calcium channel pattern and the period of target innervation suggests possible roles of T‐, N‐ and L‐type currents during developmental key events such as natural neurone death and onset of synapse formation.
Development and characterization of antibodies directed against the mouse D4 dopamine receptor
Authors: Mauger C. , Sivan B. , Brockhaus M. , Fuchs S. , Civelli O. , Monsma F. 
Published: March 2003

AbstractPolyclonal antibodies against the mouse D4 dopamine receptor have been developed in order to investigate the anatomical localization of this receptor in the mouse brain. Two antibodies were generated against specific peptides corresponding to predicted extracellular and intracellular regions of the D4 protein. Specificity of these antibodies was demonstrated on human embryonic kidney 293 (HEK 293) cells transfected with different dopamine receptor subtypes; immunoreactivity was detected only in cells transfected with the mouse D4 dopamine receptor cDNA. Following in vitro transcription/translation of the mouse D4 cDNA, a single protein band of 36 kDa was selectively immunoprecipitated with the anti‐D4 antibodies. The antibodies also detected a single protein of 36 kDa in Western blot of HEK 293 cells transiently transfected with the mouse D4 receptor. These antibodies were able to detect the D4 receptor in several regions of the mouse brain. In the regions examined, D4 immunoreactivity was found in neurones located in layers II–VI of the frontal and piriform cortices, with the highest concentration in layer II; in scattered neurones in the caudate putamen and in larger neurones in the globus pallidus. In all experiments, both antibodies exhibit the same specificity, and all immunoreactivity could be abolished by preincubation with the corresponding peptide antigen.
High‐affinity copper block of GABAA receptor‐mediated currents in acutely isolated cerebellar Purkinje cells of the rat
Authors: Sharonova Irina N. , Vorobjev Vladimir S. , Haas Helmut L. 
Published: March 2003

AbstractThe actions of Cu2+ ions on GABAA receptor‐mediated currents in acutely isolated Purkinje cells from rat cerebellum were studied using the whole‐cell patch‐clamp technique and a rapid perfusion system. Bath application of Cu2+ reduced currents induced by 2 μmγ‐aminobutyric acid (GABA) in a concentration‐dependent manner with an IC50 of 35 n
m. The Cu2+‐induced block of GABA responses was not voltage‐dependent. Increasing the GABA concentration (from 2 to 50 μm) decreased the blocking effect of Cu2+. Dose–response analysis for activation of GABAA receptors revealed a twofold decrease in apparent affinity for GABA in the presence of 0.1 μm Cu2+. Recovery from the block required several minutes after removal of Cu2+ from the medium. The block was removed by histidine, which preferentially forms complexes with Cu2+, or by other chelating substances. Application of 10 μm histidine immediately before application of 2 μm GABA completely relieved the block of GABA responses produced by 0.1 μm Cu2+. The effect of histidine was concentration‐dependent with an EC50 of 0.75 μm. The results demonstrate that Cu2+ is a potent inhibitor of GABA‐evoked responses in rat Purkinje cells. Copper may be an endogenous synaptic modulating factor. Cu2+ toxicity, notably in Wilson’s disease, could result to some extent from chronic GABAA receptor blockade.
Reversible impairment of long‐term potentiation in transgenic Cu/Zn‐SOD mice
Authors: Gahtan E. , Auerbach J.M. , Groner Y. , Segal M. 
Published: March 2003

AbstractCopper/zinc superoxide dismutase (CuZn‐SOD) is a key enzyme in the metabolism of oxygen free radicals. The gene encoding CuZn‐SOD resides on human chromosome 21 and is overexpressed in Down syndrome (DS) patients. Overexpression of CuZn‐SOD in transgenic (Tg) mice and cultured cells creates chronic oxidative stress leading to enhanced susceptibility to degeneration and apoptotic cell death. We have now found that three lines of Tg‐CuZn‐SOD mice, one of which also overexpresses S100β, a glial calcium binding protein, are deficient in spatial memory. Furthermore, hippocampal slices taken from these mice have an apparently normal synaptic physiology, but are impaired in the ability to express long‐term potentiation (LTP). This effect on hippocampal LTP was abrogated by treatment of slices with the H2O2 scavenger catalase or the antioxidant N‐t‐butyl‐phenylnitrone (BPN). It is proposed that elevated CuZnSOD causes an increase in tetanic stimulation‐evoked formation of H2O2 which leads to diminished LTP and cognitive deficits in these mice.
CRE and TRE sequences of the rat tyrosine hydroxylase promoter are required for TH basal expression in adult mice but not in the embryo
Authors: Trocmé Caryn , Sarkis Chamsy , Hermel Jean‐Michel , Duchateau René , Harrison Stephen , Simonneau Michel , Al‐Shawi Raya , Mallet Jacques 
Published: March 2003

AbstractTyrosine hydroxylase (TH), the rate‐limiting enzyme in the biosynthesis of catecholamine neurotransmitters, is expressed in a restricted number of areas, and subject to numerous regulations during development and in adulthood. Two transcription factor binding sites present in the proximal region of the TH gene, the TPA‐responsive element (TRE) and the c‐AMP responsive element (CRE), have been shown to play important roles in TH gene regulation in vitro. In order to elucidate in vivo the role of these two sites, we produced transgenic mice bearing a 5.3‐kb fragment from the 5′ flanking sequence of the TH gene with mutations in either the CRE‐ or TRE‐sites. Using the intact 5.3‐kb fragment fused to two different reporter genes (HSV1‐tk and lacZ), we show that this promoter fragment is able to specifically direct expression in catecholaminergic tissues both in adult mice and embryos. Interestingly, the CRE‐ and TRE‐mutated transgenes were not expressed in adult mice, contrary to the situation in embryos where they were specifically expressed in catecholaminergic regions. These results demonstrate that the CRE and TRE play an essential role in basal TH expression in adult tissues in vivo. Moreover, they suggest that distinct transcription factors are involved in TH regulation in developing and adult tissues. In support of this, gel mobility shift experiments revealed a complex present only in embryonic tissues. Taken together, these data highlight the diversity of the mechanisms underlying the establishment and maintenance of the catecholaminergic phenotype.
Influence of automatic word reading on motor control
Authors: Gentilucci Maurizio , Gangitano Massimo 
Published: March 2003

AbstractWe investigated the possible influence of automatic word reading on processes of visuo‐motor transformation. Six subjects were required to reach and grasp a rod on whose visible face the word ‘long’ or ‘short’ was printed. Word reading was not explicitly required. In order to induce subjects to visually analyse the object trial by trial, object position and size were randomly varied during the experimental session. The kinematics of the reaching component was affected by word presentation. Peak acceleration, peak velocity, and peak deceleration of arm were higher for the word ‘long’ with respect to the word ‘short’. That is, during the initial movement phase subjects automatically associated the meaning of the word with the distance to be covered and activated a motor program for a farther and/or nearer object position. During the final movement phase, subjects modified the braking forces (deceleration) in order to correct the initial error. No effect of the words on the grasp component was observed. These results suggest a possible influence of cognitive functions on motor control and seem to contrast with the notion that the analyses executed in the ventral and dorsal cortical visual streams are different and independent.
Anticonvulsant properties of BIBP3226, a non‐peptide selective antagonist at neuropeptide Y Y1 receptors
Authors: Gariboldi Marco , Conti Mirco , Cavaleri Davide , Samanin Rosario , Vezzani Annamaria 
Published: March 2003

AbstractSeveral lines of evidence indicate that neuropeptide Y (NPY)‐mediated neurotransmission in the hippocampus is altered by limbic seizures. The functional consequences of this change are still unresolved and clearly depend on the type of NPY receptors involved. We have investigated the role of NPY Y1 receptor subtypes, which are enriched in the dentate area of the hippocampus, on EEG seizures induced by a local injection of 0.04 μg kainic acid in rats.Intrahippocampal administration of 10 μg BIBP3226 (N2‐ (diphenylacetyl)‐N‐[(4‐hydroxyphenyl)methyl]d‐arginamide), a non‐peptide selective antagonist at the NPY Y1 receptors, increased threefold on average (P < 0.01) the time to onset of seizures and reduced the number of seizures and the total time in seizures three‐ and fourfold, respectively (P < 0.01). Its inactive S‐enantiomer BIBP3435 was ineffective on seizure activity. One microgram [Leu31,Pro34]NPY, an agonist at Y1 receptors, did not modify per se the EEG sequelae induced by kainic acid but it antagonized the anticonvulsant effect of BIBP3226.These results indicate that NPY Y1 receptors in the hippocampus are involved in epileptic phenomena and suggest that selective Y1 receptor antagonists may be of value for attenuating limbic seizures.