bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Glutamate‐induced Neurotoxicity by a Tau Antisense Oligonucleotide in Primary Culture of Rat Cerebellar Granule Cells
Authors: Pizzi Marina , Valerio Alessandra , Arrighi Virginia , Galli Paola , Belloni Marco , Ribola Marina , Alberici Antonella , Spano PierFranco , Memo Maurizio 
Published: April 2006

AbstractShort‐term exposure of primary cultures of cerebellar granule cells from neonatal rat brain to high concentrations of glutamate resulted in a significant increase of both immunoreactivity to and mRNA levels of tau protein. Time‐course experiments revealed the increases of tau immunoreactivity and mRNA levels to be maximal 2 h after the glutamate pulse. To investigate the relationship between newly synthesized tau protein and glutamate‐induced neurotoxicity, neurons were preincubated with a specific tau antisense oligonucleotide. This treatment resulted in (i) inhibition of the glutamate‐induced increase of tau immunoreactivity and (ii) a decrease in the sensitivity of the neurons to neurotoxic concentrations of glutamate. These data indicate that induction of the cytoskeleton‐associated tau protein participates in the cascade of events promoted by glutamate leading to neurodegeneration.
NMDA and Kainate Induce Internucleosomal DNA Cleavage Associated With Both Apoptotic and Necrotic Cell Death in the Neonatal Rat Brain
Authors: van Lookeren Campagne M. , Lucassen P. J. , Vermeulen J. P. , Balazs R. 
Published: April 2006

AbstractInjection of N‐methyl‐D‐aspartate (NMDA) or kainate in the striatum of 7‐day‐old rats induced massive cell loss in the ipsilateral striatum, hippocampus and inner cortical layers. In order to examine whether apoptosis contributes to cell death in this model of excitotoxic injury we examined the progression of internucleosomal DNA fragmentation and changes in cellular ultrastructure. Agarose gel electrophoresis of DNA extracted from the ipsilateral striatum, cerebral cortex and hippocampus clearly showed breakdown of DNA into oligonucleosome‐sized fragments, indicative of apoptosis, 12 h post‐NMDA injection. In addition, an increase between 12 and 24 h was observed as well as a continuous presence 5 days later. Kainate induced a similar time course of oligonucleosomal DNA fragmentation, but the intensity of the ethidium bromide stained bands was less compared with that observed for NMDA. DNA fragmentation was not detected in animals intrastriatally injected with Tris‐HCl or in animals treated with MK‐801 [(+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohept‐5,10‐imine hydrogen maleate, 1 mg/kg] 30 min after NMDA injection. MK‐801 had no effect on DNA fragmentation induced by kainate. In addition to agarose gel electrophoresis, terminal deoxynucleotidyltransferase‐mediated dUTP‐biotin nick end labelling (TUNEL) was used for detection of DNA fragmentation in sections. A gradual increase in the density of both apoptotic and non‐apoptotic TUNEL nuclei was found in the anterior cingulate (ACC) and retrosplenial (RSC) areas of the cortex, the striatum, and the CA1 area and dentate gyrus of the hippocampus over the first 24 h post‐NMDA or kainate injection. In the contralateral hemisphere hardly any TUNEL nuclei were present and their density was comparable with that in animals injected with vehicle only. In the ipsilateral mammillary nucleus (MN), which showed no signs of acute cell swelling after intrastriatal injection with NMDA, internucleosomal DNA fragmentation was found 24 and 48 h after intrastriatal NMDA injection. Here, the density of TUNEL cells with apoptotic morphology was high at 12 and 24 h post‐NMDA injection but returned to control levels by 5 days. Electron microscopy showed cells with a clearly apoptotic morphology in the ACC and RSC and in the MN 24 h after NMDA injection. In the CA1 area of the hippocampus a necrotic, rather than an apoptotic, ultrastructure prevailed, indicating that the TUNEL method stained both apoptotic and necrotic cells. Based on biochemical and morphological criteria this study provides strong evidence that both apoptosis and necrosis are involved in NMDA‐ or kainate‐induced excitotoxic cell death in the neonatal rat brain.
Brain Structure and Task‐specific Increase in Expression of the Gene Encoding Syntaxin 1B During Learning in the Rat: A Potential Molecular Marker for Learning‐induced Synaptic Plasticity in Neural Networks
Authors: Davis S. , Rodger J. , Hicks A. , Mallet J. , Laroche S. 
Published: April 2006

AbstractThe mRNAs encoding the synaptic vesicle proteins syntaxin 1 B and synapsin I were measured using in situ hybridization in several brain regions‐the dentate gyrus, CA3 and CA1 of the hippocampus, the parietal, the motor and prefrontal cortices and the core and shell of the accumbens‐of rats that were learning a spatial reference or working memory task on a radial arm maze. The mRNA encoding syntaxin 1B was significantly increased in all hippocampal regions in rats learning the working memory task, whereas it was increased in the prelimbic area of the prefrontal cortex and the shell of the accumbens in rats learning the spatial reference memory task. No change in mRNA encoding syntaxin 1B was observed in the motor and parietal cortices or the core of the accumbens, and the mRNA encoding synapsin I was not significantly different from that of naive caged controls or rats running the maze for continuous reinforcement in any of the brain structures examined. These results demonstrate that the gene encoding a key member of synaptic vesicle function is up‐regulated in a task‐ and brain‐specific manner during learning. They are discussed in terms of the potential role this protein may play in trans‐synaptic propagation of plasticity within specific neural networks as a function of the information required in the laying down of different types of memory.
Two Glutamate Decarboxylase Forms Corresponding to the Mammalian GAD65 and GAD67 are Expressed During Development of the Chick Telencephalon
Authors: Åhman Anna‐Karin , Wågberg Fredrik , Mattsson Mats‐Olof 
Published: April 2006

AbstractThe γ‐aminobutyric acid (GABA)‐synthesizing enzyme glutamate decarboxylase (GAD) was studied during development of the chick telencephalon. By means of reverse‐phase HPLC analysis, we showed that GABA indeed accumulates during embryogenesis, whereas the levels of glutamate, the substrate for GAD, are more or less unchanged up to later developmental stages. The enzyme activity increased ∼25‐fold from embryonic day 3 to embryonic day 17. Immunoblotting data revealed that two GAD proteins, of ∼65 and 67 kDa, were present during the period investigated. Furthermore, Northern blot analysis with probes obtained from rat cDNA sequences, as well as a chicken‐specific probe for GAD65 generated by means of reverse transcriptase‐polymerase chain reaction (RT‐PCR), strengthened the interpretation that the chick embryo expresses genes corresponding to GAD65 and GAD67. The rat probes recognized transcript sizes of 3.9 kb (GAD65) and 5.6 kb (GAD67), sizes which are different from those of the rat brain (Erlander et al., Neuron, 7, 91−100, 1991). Sequencing of the RT‐PCR products revealed a high level of homology (82% at the nucleotide level) between the mammalian and chick GAD65 genes. Taken together, these findings suggest that the chick embryo expresses two GAD genes during embryogenesis. The functional properties of each gene product remain to be investigated.
Selective Depletion of Clear Synaptic Vesicles and Enhanced Quantal Transmitter Release at Frog Motor Nerve Endings Produced by Trachynilysin, a Protein Toxin Isolated from Stonefish (Synanceia trachynis) Venom
Authors: Colasante Cesare , Meunier Frédéric A. , Kreger Arnold S. , Molgó Jordi 
Published: April 2006

AbstractOur previous observation that low concentrations of stonefish (Synanceia trachynis) venom elicit spontaneous quantal acetylcholine release from vertebrate motor nerve terminals prompted our present study to purify the quantal transmitter‐releasing toxin present in the venom and to characterize the toxin's ability to alter the ultrastructure and immunoreactivity of frog motor nerve terminals. Fractionation of S. trachynis venom by sequential anion exchange fast protein‐liquid chromatography (FPLC) and size‐exclusion FPLC yielded a highly purified preparation of a membrane‐perturbing (haemolytic) protein toxin, named trachynilysin. Trachynilysin (2–20 μg/ml) significantly increased spontaneous quantal acetylcholine release from motor endings, as detected by recording miniature endplate potentials from isolated frog cutaneous pectoris neuromuscular preparations. Ultrastructural analysis of nerve terminals in which quantal acetylcholine release was stimulated to exhaustion by 3 h exposure to trachynilysin revealed swelling of nerve terminals and marked depletion of small clear synaptic vesicles. However, trachynilysin did not induce a parallel depletion of large dense‐core vesicles. Large dense‐core vesicles contained calcitonin gene‐related peptide (CGRP), as revealed by colloidal gold immunostaining, and trachynilysin‐treated nerve endings exhibited CGRP‐like immunofluorescence similar to that of untreated terminals. Our results indicate that the ability of stonefish venom to elicit spontaneous quantal acetylcholine release from vertebrate motor nerve terminals is a function of trachynilysin, which selectively stimulates the release of small clear synaptic vesicles and impairs the recycling of small clear synaptic vesicles but does not affect the release of large dense‐core vesicles. Trachynilysin may be a valuable tool for use in other secretory terminals to discriminate between neurotransmitter and neuropeptide release.
Zinc Modulation of Bicuculline‐sensitive and ‐insensitive GABA Receptors in the Developing Rat Hippocampus
Authors: Martina Marco , Mozrzymas Jerzy W. , Strata Fabrizio , Cherubini Enrico 
Published: April 2006

AbstractIntracellular recordings were used to study the effects of zinc on the bicuculline‐sensitive and ‐insensitive responses evoked by GABA in CA3 rat hippocampal neurons in slices obtained from postnatal day (P) 0 to P8. In the absence of bicuculline, zinc inhibited GABA‐induced responses in a concentration‐dependent manner. This effect was developmentally regulated, being maximal (50%) between P0 and P5 and then declining to 30% after P5. In the presence of bicuculline, GABA‐resistant responses were potentiated in 49% of cases, depressed in 38% and not affected in 13%. The period of maximum potentiation between P0 and P2 coincided with that of maximum expression of the bicuculline‐resistant receptors. The effects of zinc were also studied using the whole‐cell and outside‐out configuration of the patch‐clamp technique on bicuculline‐sensitive and ‐insensitive GABA‐induced currents elicited in isolated cells acutely dissociated from the same slices as those used for intracellular recordings. At a holding potential of ‐50 mV in symmetrical chloride solutions, GABA (50 and 100 μM) activated whole‐cell inward currents which were reversibly blocked by zinc. The EC50 values for the blocking effect of zinc on currents evoked by 50 and 100 μM GABA were 6.6 nM and 5.8 μM respectively. In the presence of bicuculline (100 μM), zinc potentiated the residual responses to GABA; the response curve was bell‐shaped with a peak at 1 μM. When the response to GABA was completely abolished by bicuculline, zinc (1 μM) was often able to restore it. In the presence of bicuculline, however, zinc was not able to restore the response to isoguvacine. In two excised outside‐out patches, zinc (1 μM) increased the activity of opening of bicuculline‐resistant GABA‐evoked single channel currents (Np) from 1 to 1.87 and from 0.25 to 0.42 respectively, without changing single‐channel conductance. These data suggest that down‐ or up‐regulation of bicuculline‐sensitive or ‐insensitive GABA receptors may be functionally important in regulating synaptic activity during development.
Olfactory Bulb Repetitive Stimulations Reveal Non‐homogeneous Distribution of the Inhibitory Processes in the Rat Piriform Cortex
Authors: Litaudon P. , Cattarelli M. 
Published: April 2006

AbstractOptical signals were recorded in the in vivo rat piriform cortex in response to a burst of seven electrical stimulations (100 ms interval) delivered in the olfactory bulb. Based on the recorded responses, three types of signal could be identified according to the relative amplitude of their monosynaptic and disynaptic components. The disynaptic component had a larger (type 1) or an equal amplitude (type 2) compared with the monosynaptic one. Type 3 exhibited only the monosynaptic component. Type 1 represented 96% of the first response. The second response was characterized by an increase in type 3 signals (39%). The remaining type 1 signals were lower in amplitude when compared with the first response. The responses to the last five stimulations did not differ from one another but were different from the first two (type 1, 74%; type 2, 7.8%; type 3, 18.2% on average). The spatial distribution of these three types of signal was analysed by dividing the piriform cortex into several areas. These areas were not homogeneous in the percentage of each signal type: the percentage of type 3 signals was highest (˜30%) in the area near the lateral olfactory tract and <10% in the most posterodorsal area. Thus the level of inhibition remained high in some piriform areas whereas it decreased rapidly in others, suggesting that the inhibitory processes were not homogeneously distributed in the whole piriform cortex. Functional implications are discussed.
Responses of Neurons of the Nucleus of the Optic Tract and the Dorsal Terminal Nucleus of the Accessory Optic Tract in the Awake Monkey
Authors: Ilg Uwe J. , Hoffmann Klaus‐Peter 
Published: April 2006

AbstractThe nucleus of the optic tract (NOT) and the dorsal terminal nucleus of the accessory optic tract (DTN) are essential nuclei for the generation of slow‐phase eye movements during horizontal optokinetic nystagmus. We recorded from 101 neurons (all directionally selective) in four NOT/DTN of three trained and behaving rhesus monkeys. Neuronal activity increased when stimuli moved ipsiversively with respect to the recording site and decreased below spontaneous activity when stimuli moved contraversively. While the monkey fixated a small spot, some NOT/DTN neurons did not respond at all to the retinal image slip of a whole‐field random dot pattern; others showed a monotonic increase of activity to increasing velocities of that stimulus. The velocity range tested was up to 100°/s. During the execution of optokinetic nystagmus, 39 of 73 cells tested showed a velocity‐tuned response with an average optimum at 21°/s retinal image slip. Following saccades during optokinetic nystagmus (quick phases), the NOT/DTN neuronal activity briefly attained the level of spontaneous activity, as predicted from the velocity selectivity during optokinetic nystagmus. Immediately upon cessation of optokinetic stimulation in the preferred direction, NOT/DTN activity returned to the spontaneous level and did not reflect the ongoing optokinetic afternystagmus in darkness. Most NOT/DTN neurons displayed direction selectivity also during smooth pursuit. Twenty‐one of 50 cells tested (42%) always responded to the retinal slip of the target (target velocity cells), 16 cells (32%) responded to the retinal slip of the background (background velocity cells), and 13 cells (26%) did not respond at all during smooth pursuit. We conclude from our results that the NOT/DTN is an essential structure for the processing of the direction and speed of retinal image slip. This information is then used for the generation and maintenance of slow eye movements, preferentially during horizontal optokinetic nystagmus but also during pursuit eye movements.
Mechanisms for Synchronous Calcium Oscillations in Cultured Rat Cerebellar Neurons
Authors: Nuñez Lucia , Sanchez Ana , Fonteriz Rosalba I. , Garcia‐Sancho Javier 
Published: April 2006

AbstractRemoval of Mg2+ caused oscillations of the cytosolic Ca2+ concentration ([Ca2+]i) and the membrane potential in cultured cerebellar granule neurons. Oscillations of [Ca2+]i were synchronous in all the cells, and were restricted to the neurons (immunocytochemically identified) that responded to exogenous N‐methyl‐D‐aspartate (NMDA). Oscillations were blocked by Ca2+ removal, nickel, NMDA receptor antagonists, ω‐agatoxin IVA, tetrodotoxin, sodium removal and γ‐aminobutyric acid, but not by dihydropyridines, ω‐conotoxin M VIIA or by emptying the intracellular Ca2+ stores with thapsigargin or ionomycin. The upstroke of the [Ca2+]i oscillations coincided in time with an increase in manganese permeability of the plasma membrane. Propagation of the [Ca2+]i wave followed more than one pathway and the spatiotemporal pattern changed with time. Membrane potential oscillations consisted of transient slow depolarizations of ˜20 mV with faster phasic activity superimposed. We propose that the synchronous [Ca2+]i oscillations are the expression of irradiation of random excitation through a neuronal network requiring generation of action potentials and functional glutamatergic synapses. Oscillations of [Ca2+]i are due to cyclic Ca2+ entry through NMDA receptor channels activated by synaptic release of glutamate, which requires Ca2+ entry through P‐type Ca2+ channels activated by action potentials at the presynaptic terminal.
TGF‐β Rescues Target‐deprived Preganglionic Sympathetic Neurons in the Spinal Cord
Authors: Blottner Dieter , Wolf Nicole , Lachmund Astrid , Flanders Kathleen C. , Unsicker Klaus 
Published: April 2006

AbstractTransforming growth factors β (TGF‐β), a family of pleiotropic cytokines, are widely distributed in the developing and adult nervous system. In order to further determine the neural functions of TGF‐β, we have localized the TGF‐β isoforms 1, 2 and 3 in the adult rat adrenal medulla and studied the neuroprotective capacity of one representative family member, TGF‐β2, for those spinal cord neurons which innervate adrenal chromaffin cells and which die after destruction of the adrenal medulla. Unilateral electrothermal destruction of the adrenal medulla led to the disappearance of 25% of sympathetic preganglionic neurons, which are located in the intermediolateral (IML) column of thoracic spinal cord segments 7–10 and can be selectively marked by NADPH‐diaphorase. The neurons which disappeared following adrenomedullectomy constitute the full set of neurons that innervate the adrenal medulla. Implantation of gelfoam soaked with 0.5 μg TGF‐β2 into the adrenal wound cavity rescued all spinal cord neurons in the IML ipsilaterally to the lesioned side. Cytochrome c was not effective. Injections of [125l]TGF‐β2 into the adrenal medulla did not result in retrograde transport and subsequent labelling of spinal cord neurons, suggesting that TGF‐β may exert its neuroprotective actions by indirect mechanisms. TGF‐β applied to cultured adrenocortical cells did not overtly increase the amount of mRNA for fibroblast growth factor‐2, an established trophic molecule for sympathetic preganglionic spinal cord neurons. The mechanisms by which TGF‐β exerts its neurotrophic effect are therefore unclear. Even so, our data provide the first evidence that TGF‐β may play an important role in vivo in the control of maintenance of a population of spinal cord neurons.
Cholinergic Modulation of the Action Potential in Rat Hippocampal Neurons
Authors: Figenschou Anne , Hu Guo‐Yuan , Storm Johan F. 
Published: April 2006

AbstractThe cholinergic input to the hippocampus from the medial septum is important for modulating hippocampal activity and functions, including theta rhythm and spatial learning. Neuromodulation by transmitters in central nervous system neurons usually affects cell excitability by modifying the membrane potential, discharge pattern and spike frequency. Here we describe another type of neuromodulation: changing the action potential waveform. During intracellular recordings from CA1 pyramidal cells in hippocampal slices from rats, the cholinergic agonist carbachol caused several reversible changes in the action potential: low doses (2 μM) caused an increase in spike duration; high doses (10–40 μM) or long‐lasting applications also reduced the spike amplitude and rate of rise, and raised the spike threshold. These effects are similar to those of metabotropic glutamate receptor agonists or phorbol esters, both of which activate protein kinase C. The effects were blocked by the muscarinic antagonist atropine, and were prevented by Ca2+‐free medium and by Ca2+‐channel blockers. However, the cholinergic spike modulation was not occluded or mimicked by blocking the Ca2+‐dependent K+ currents Ic or IAHP, suggesting that these K+ currents are not involved in the modulation.
Differential Localization of AMPA Glutamate Receptor Subunits in the Two Segments of the Globus Pallidus and the Substantia Nigra Pars Reticulata in the Squirrel Monkey
Authors: Paquet Maryse , Smith Yoland 
Published: April 2006

AbstractThe subthalamic nucleus has long been known as the main source of glutamatergic afferents to the pallidum and the substantia nigra in primates. Recent findings showed that the excitatory effects induced by the subthalamic nucleus in pallidal cells are mediated through the activation of non‐NMDA receptors in the rat. The objective of the present study was to analyse the distribution of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionate (AMPA) glutamate receptor subunits in the external pallidum (GPe), the internal pallidum (GPi) and the substantia nigra pars reticulata (SNr) in squirrel monkeys (Saimiri sciureus). This was achieved by means of immunohistochemistry using antibodies raised against the GluR1 and the GluR2/3 subunits of the AMPA receptor. Our results show that all neuronal perikarya in GPe and GPi display immunoreactivity for GluR2/3 subunits whereas GluR1 is confined exclusively to cells in the GPe. The proportion of GluR1‐immunoreactive neurons is not uniform throughout the rostrocaudal extent of GPe; in the rostral third all GPe cells display GluR1 immunoreactivity, whereas in the caudal third the proportion of GluR1‐positive cells decreases to 50%. The intensity of GluR1 immunostaining associated with GPe cells is lower than that associated with neighbouring large‐sized neurons in the nucleus basalis of Meynert. In contrast to GPi cells, the neurons in the SNr display immunoreactivity for both GluR1 and GluR2/3 subunits. In conclusion, our results provide the first evidence for a different distribution of the GluR1 subunit of the AMPA receptors in the two segments of the globus pallidus in monkeys. These findings imply that the control of the basal activity of GPe and GPi cells by the subthalamic nucleus is exerted via the activation of AMPA receptors composed of different subunits. These data reinforce the view that the two segments of the globus pallidus are different entities that possess their own functional characteristics in primates.
A Critique of a New Analysis Proposed for Functional Neuroimaging
Authors: Frackowiak R. S. J. , Zeki S. , Poline J.‐B. , Friston K. J. 
Published: April 2006

AbstractMethods for analysing functional imaging data have evolved rapidly over the last ten years. Standardized techniques based on formal mathematical and statistical theory and rigorous empirical validation have been proposed to facilitate comparisons of biological results between laboratories. This paper examines an image analysis technique that appears to identify unexpectedly large numbers of activated brain areas for the data collected. It concludes that the method may not adequately control for false positives, rendering interpretation of the functional anatomy difficult.