bluuebunny/crossref_metadata_2025_split huggingface dataset:
NGF Deprivation of Adult Rat Brain Results in Cholinergic Hypofunction and Selective Impairments in Spatial Learning
Authors: Van der Zee Catharina E. E. M. , Lourenssen Sandra , Stanisz Jolanta , Diamond Jack 
Published: April 2006

AbstractCholinergic hypofunction has often been correlated with a variety of behavioural impairments. In the present study, adult Wistar rats were intraventricularly infused with antibodies to nerve growth factor (anti‐NGF) to examine the effects on cholinergic neurons of the basal forebrain, and on behavioural performance. Immunocytochemical techniques indicated that chronically infused anti‐NGF penetrates into the basal forebrain, cortex, striatum, corpus callosum and hippocampus, confirming previous findings after a single injection. Treatment with anti‐NGF for 1 or 2 weeks resulted in a significant decrease of 27‐33% in density of choline acetyltransferase immunostaining of the cholinergic cell bodies in the medial septum and vertical diagonal band, and a 26% reduction in choline acetyltransferase enzyme activity in the septal area. An array of spatial learning Morris water maze tasks was used to distinguish between acquisition skills and the flexible use of learned information in novel tests. Rats subjected to the spatial learning paradigm received anti‐NGF infusion for 2 weeks prior to and for another 2 weeks during the behavioural testing. The anti‐NGF‐treated animals were found to be no different from those receiving control serum in the Morris water maze acquisition task, either in the latency to find the platform or in the time spent searching in the training quadrant when the platform was removed. However, in consecutive extinction trials, anti‐NGF rats continued to search in the empty training quadrant, suggesting the occurrence of perseveration; control rats expanded their search over other areas of the pool. This inflexibility of the anti‐NGF rats was also evident from their difficulty in learning to find a relocated platform in the reversal task. Finally, the anti‐NGF‐treated animals demonstrated hyperactivity in the open field, resembling in this respect the behaviour of animals after septal and fimbria fornix lesions, and during pharmacological cholinergic blockade. While these data support a role for NGF in cholinergic function and spatial learning behaviour, they indicate that deficits in the latter, e.g. those demonstrated in impaired aged rats, may not be attributable selectively to deficits in the function of NGF‐sensitive cholinergic neurons of the basal forebrain.
Exocytosis and Selective Neurite Calcium Responses in Rat Cerebellar Granule Cells During Field Stimulation
Authors: Cousin Michael A. , Held Brigitte , Nicholls David G. 
Published: April 2006

AbstractThe free calcium concentration, [Ca2+]c, in fura‐2‐loaded rat cerebellar granule cells was investigated by digital imaging during trains of uniform field stimuli in order to compare the ability of calcium channels in somata and neurites to respond to brief, physiologically relevant depolarizations. Very few somata responded to 20 Hz trains of 1 ms pulses, while virtually all neurites showed an extensive increase which was rapidly reversed when stimulation was terminated. In contrast, both somata and neurites responded when cells were depolarized with 50 mM KCl. The field stimuli evoked a tetrodotoxin‐sensitive increase in Na+ concentration in both somata and neurites. When 4‐aminopyridine, which inhibits delayed K+ currents in these cells, was present during the field stimulus both somata and neurites increased their [Ca2+]c, suggesting that prolongation of the duration of depolarization is required for somatic Ca2+ channel activation. The neurite response did not depend on the orientation of the neurite relative to the applied field. The neurite response was insensitive to nifedipine (1 μM) and ω‐agatoxin‐IVA (30 nM) but was uniformly inhibited by ω‐conotoxin‐GVIA (30% inhibition at 1 μM) and ω‐conotoxin‐MVIIC (44% inhibition at 5 μM). The two inhibitors were not additive. The neurite [Ca2+]c response was insensitive to the combination of ionotropic glutamate receptor antagonists. Field stimulation caused the exocytosis of the fluorescent probe FM1‐43 previously loaded during KCl depolarization, suggesting that presynaptic Ca2+ channels contribute to the field‐evoked neurite response.
Ammonia Prevents Activation of NMDA Receptors by Glutamate in Rat Cerebellar Neuronal Cultures
Authors: Marcaida Goizane , Miñana María‐Dolores , Burgal María , Grisolía Santiago , Felipo Vicente 
Published: April 2006

AbstractAcute ammonia toxicity is mediated by activation of NMDA receptors and is prevented by chronic moderate hyperammonaemia. The aim of this work was to assess whether the protective effect of chronic hyperammonaemia is due to impaired activation of the NMDA receptor. It is shown that chronic hyperammonaemia in rats decreases the binding of [3H]MK‐801 to synaptosomal membranes from the hippocampus but not the amount of NMDAR1 receptor protein as determined by immunoblotting. In primary cultures of cerebellar neurons, long‐term treatment with 1 mM ammonia also decreased significantly the binding of [3H]MK‐801. These results suggest that ammonia impairs NMDA receptor activation. To confirm this possibility we tested the effect of long‐term treatment of the cultured neurons with 1 mM ammonia on three well known events evoked by activation of the NMDA receptor: neuronal death induced by glutamate, increase in aspartate aminotransferase activity and increase in free intracellular [Ca2+]. Long‐term treatment with ammonia prevented noticeably the effects of glutamate or NMDA on all these parameters. These results indicate that long‐term treatment of neurons with 1 mM ammonia leads to impaired function of the NMDA receptor, which cannot be activated by glutamate or NMDA. Activation of protein kinase C by a phorbol ester restored the ability of the NMDA receptor to be activated in neurons treated with ammonia. This suggests that ammonia impairs NMDA receptor function by decreasing protein kinase C‐dependent phosphorylation.
An NK1 Receptor‐dependent Component of the Slow Excitation Recorded Intracellularly from Rat Motoneurons Following Dorsal Root Stimulation
Authors: Baranauskas G. , Traversa U. , Rosati A. M. , Nistri A. 
Published: April 2006

AbstractIntracellular recording from lumbar motoneurons of the neonatal rat spinal cord in vitro was used to study how recently developed non‐peptide antagonists such as SR‐140333 and SR‐48698, known to block distinct subtypes of tachykinin receptors peripherally, might affect synaptic transmission elicited by electrical stimulation of dorsal root fibres. SR‐140333 (1 μM) preferentially antagonized responses mediated by an exogenously applied agonist acting on the NK1 receptor subclass, while SR‐48968 (0.5 μM) preferentially reduced responses mediated by an exogenously applied agonist acting on the NK2 receptor subclass. SR‐48968 did not affect fast or slow excitatory postsynaptic potentials (EPSPs) or ‘wind‐up’responses induced by repetitive, low‐frequency stimulation (mimicking certain types of nociceptive input); binding studies using this radiolabelled ligand disclosed specific binding activity (21 fmol/mg protein) selectively displaced by an NK2 receptor agonist. SR‐140333 reduced the late component of fast and slow EPSPs, and of wind‐up. Pharmacological block of ionotropic glutamate receptors abolished all dorsal root‐evoked EPSPs. In comparison to glutamate receptor blockers, SR‐140333 was a weaker antagonist of slow synaptic responses, though it displayed preferential antagonism towards some components of the wind‐up phenomenon. The present results provide evidence obtained with a novel NK1 antagonist that a neuropeptide (presumably substance P), although not directly released by primary afferents onto motoneurons, is a neurotransmitter (acting via NK1 receptors) in the pathway mediating slow synaptic responses of motoneurons, and is presumably involved in signalling nociceptive inputs from the periphery.
Discriminative Cues Indicating Reward Magnitude Continue to Determine Reaction Time of Rats Following Lesions of the Nucleus Accumbens
Authors: Brown Verity J. , Bowman Eric M. 
Published: April 2006

AbstractThe role of the nucleus accumbens in incentive motivation is accepted but poorly understood. In this study, we examined in the rat one aspect of motivated behaviour which might be mediated by the nucleus accumbens, namely the translation of a motivational signal (the expected value of a reward) into motor output (responding for the reward). Rats were trained in a reaction time task in which on each trial they received one, two or three pellets. The number of pellets for each trial was randomly determined in advance and signalled to the rats by cue lights. Rats responded with faster reaction times as the size of the expected reward increased. Following ibotenic acid lesions of the nucleus accumbens, there was no difference in the pattern or the speed of reaction times. Although lesions of the nucleus accumbens did not disconnect the motivational system from the motor system, it is possible that the nucleus accumbens is involved in the learning of the incentive salience of external stimuli. Therefore, after postoperative testing the cue contingencies were reversed. Initially, the cues continued to be interpreted according to their prior significance, but eventually both the lesioned rats and the control group acquired the new relationship and did so in equivalent times. We conclude that the nucleus accumbens is not involved in the acquisition or expression of the processes whereby the expectation of rewards of different value is translated into a motor initiation signal.
Patch‐clamp Analysis of Synaptic Transmission to Cerebellar Purkinje Cells of Prion Protein Knockout Mice
Authors: Herms Jochen W. , Kretzschmar Hans A. , Titz Stefan , Keller Bernhard U. 
Published: April 2006

AbstractThe prion protein (PrP) plays a pivotal role in transmissible spongiform encephalopathies such as Creutzfeldt‐Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. Previous experiments have suggested that the normal cellular prion protein (PrPC) is involved in synaptic function in the hippocampus. Here, we utilized the controlled recording conditions of the patch‐clamp technique to investigate the synaptic function of prion protein in cerebellar Purkinje cells. By performing whole‐cell and outside‐out patch‐clamp experiments in thin slices, we investigated synaptic transmission in prion protein knockout mice (PrP‐null) and control animals. In PrP‐null mice, the kinetics of GABA‐ and glutamate receptor‐mediated currents showed no significant deviation from those in control animals. In contrast to previous results in hippocampal neurons, our findings support the view that synaptic transmission is unimpaired in prion protein‐deficient mice.
Metabotropic Glutamate Receptors Inhibiting Excitatory Synapses in the CA1 Area of Rat Hippocampus
Authors: Manzoni Olivier , Bockaert Joël 
Published: April 2006

AbstractIn the CA1 region of hippocampal slices prepared from young adult rats, we studied the ability of several specific agonists of metabotropic glutamate receptors (mGluRs) to depress excitatory synaptic transmission at the CA3–CA1 pyramidal cell synapses. Three groups of mGluRs have been described: group 1 (mGluR1 and 5) receptors are positively coupled to phospholipase C whereas group 2 (mGluR2 and 3) and group 3 (mGluR4, 6, 7 and 8) receptors are negatively coupled to adenylate cyclase. We found that the broad‐spectrum agonist (1S,3R)‐1‐aminocyclopentyl‐1,3‐dicarboxylate and the group 1‐specific agonist (R,S)‐dihydroxyphenylglycine both reversibly inhibited evoked field excitatory postsynaptic potentials, indicating the involvement of group 1 mGluRs. (R,S)‐3,5‐dihydroxyphenylglycine presumably inhibited transmission via a presynaptic mechanism, as whole‐cell voltage‐clamp recordings revealed that inhibition of the synaptic transmission was always accompanied with an increase in paired‐pulse facilitation. Treatment with a specific blocker of mGluR1 receptors, the phenylglycine derivative (S)‐4‐carboxyphenylglycine, was without effect on the (1S,3R)‐1‐amino‐cyclopentyl‐1,3‐dicarboxylate‐induced depression of the field excitatory postsynaptic potentials, strongly suggesting that mGluR5 receptors are responsible for the (1S,3R)‐1‐aminocyclopentyl‐1,3‐dicarboxylate effect. Two selective agonists of group 2 mGluRs, (2S,1′s,2′s)‐2‐(2′‐carboxycyclopropyl)glycine and 4‐carboxy‐3‐hydroxyphenylglycine, were totally ineffective in blocking CA3‐CA1‐evoked synaptic transmission, excluding the involvement of mGluR2/3 subtypes at this developmental stage.
Ischaemia‐induced Long‐term Hyperexcitability in Rat Neocortex
Authors: Luhmann Heiko J. , Mudrick‐Donnon Lori A. , Mittmann Thomas , Heinemann Uwe 
Published: April 2006

AbstractThe long‐term structural and functional consequences of transient forebrain ischaemia were studied with morphological, immunohistochemical and in vitro electrophysiological techniques in the primary somatosensory cortex of Wistar rats. After survival times of 10–17 months postischaemia, neocortical slices obtained from ischaemic animals were characterized by a pronounced neuronal hyperexcitability in comparison with untreated age‐matched controls. Extra‐and intracellular recordings in supragranular layers revealed all‐or‐none long‐latency recurrent responses to orthodromic synaptic stimulation of the afferent pathway. These responses were characterized by durations up to 1.7 s, by multiple components and by repetitive synaptic burst discharges. The reversible blockade of this late activity by dl‐aminophosphonovaleric acid (APV) suggested that this activity was mediated by Kmethyl‐l‐aspartate (NMDA) receptors. The peak conductance of inhibitory postsynaptic potentials was significantly smaller in neurons recorded in neocortical slices obtained from ischaemic animals than those from the controls. However, the average number of parvalbumin (PV)‐labelled neurons per mm3, indicative of a subpopulation of GABAergic interneurons, and the average number and length of dendritic processes arising from PV‐containing cells was not significantly different between ischaemic and control cortex. The prominent dysfunction of the inhibitory system in ischaemic animals occurred without obvious structural alterations in PV‐labelled cells, indicating that this subpopulation of GABAergic interneurons is not principally affected by ischaemia. Our data suggest a long‐term down‐regulation of inhibitory function and a concurrent NMDA receptor‐mediated hyperexcitability in ischaemic neocortex. These alterations may result from structural and/or functional properties of inhibitory non‐PV‐positive neurons or permanent functional modifications on the subcellular molecular level, i.e. alterations in the phosphorylation status of GABA and/or NMDA receptors. The net result of these long‐term changes is an imbalance between the excitatory and inhibitory systems in the ischaemic cortex with the subsequent expression and manifestation of intracortical hyperexcitability.
Initial Tract Formation in the Brain of the Chick Embryo: Selective Expression of the BEN/SC1/DM‐GRASP Cell Adhesion Molecule
Authors: Chédotal Alain , Pourquié Olivier , Sotelo Constantino 
Published: April 2006

AbstractThis study reports the spatio‐temporal pattern of BEN expression (a molecule of the immunoglobulin superfamily) during early stages of the first axonal tract formation, in the fore‐ and midbrain of chick embryos [Hamburger and Hamilton (HH) stages 12–22]. The expression of BEN has been analysed using immunohistochemistry and non‐radioactive in situ hybridization. Furthermore, double labelling experiments (combining anti‐class III β‐tubulin, a pan‐neuronal marker, and anti‐BEN antibodies) have been carried out to determine whether BEN is expressed by all first axonal tracts. The first neurons expressing BEN appear around stage HH13–14, in the caudal diencephalon. They belong to the interstitial nucleus of Cajal, and their axons are the first components of the medial longitudinal fasciculus. By HH14, two other early axonal tracts appear: the tract of the postoptic commissure and the descending root of the mesencephalic nucleus of the trigeminal nerve. Only the latter expresses BEN. At later stages of development numerous new axonal tracts appear in the telencephalic, diencephalic and mesencephalic domains. Only a few of them (the fourth nerve, the lemniscus lateralis, the tectobulbar and habenulopeduncular tracts) express BEN. In all BEN positive systems, the cell bodies, axons and growth cones are uniformly labelled by the antibody. We have found that none of the early axonal tracts grows preferentially at interneuromeric boundaries. Moreover, each tract is formed by several thin fascicles rather than a single one. The expression of BEN is transient and disappears shortly before hatching. These results suggest that BEN may serve to promote axonal outgrowth of precise neuronal systems involved in ‘axonal scaffolding’.
Radiation‐induced Reductions in Macrophage Recruitment Have Only Slight Effects on Myelin Degeneration in Sectioned Peripheral Nerves of Mice
Authors: Perry V. H. , Tsao J. W. , Feam S. , Brown M. C. 
Published: April 2006

AbstractMacrophage recruitment into the distal nerve stump of the cut or crushed sciatic or saphenous nerves of C57BL/6J mice was reduced by prior whole body irradiation. This procedure was successful in keeping the numbers of cells stained with the mouse macrophage‐specific antibody F4/80 to the levels found in unsectioned nerves. Quantitative image analysis of immunostained sections showed that the rate of loss of myelin basic protein was identical in nerves from irradiated and unirradiated mice up to 5 days but thereafter was slower in macrophage‐deprived nerves. Similar analysis of semithin sections stained with toluidine blue detected more undegenerated myelin in the nerves from irradiated mice 10 days after operation. Quantitative counts made from electron micrographs of the sectioned nerves at 7 days also showed slightly less extensive myelin breakdown in the nerves from irradiated mice. Complete removal of myelin from some Schwann cells can occur without macrophages, but macrophages accelerate the removal of myelin in the later stages of Wallerian degeneration. It is concluded that there are two phases to the breakdown of myelin in peripheral nerves undergoing Wallerian degeneration: an initial stage entirely dependent on the activity of Schwann cells and a later stage dependent on both Schwann cells and the presence of macrophages.
BDNF‐activated Sianal Transduction in Rat Cortical Glial Cells
Authors: Roback John D. , Marsh H. Nicholas , Downen Martha , Palfrey H. Clive , Wainer Bruce H. 
Published: April 2006

AbstractCortical glial cells in culture were found to be responsive to the neurotrophin brain‐derived neurotrophic factor (BDNF), as evidenced by activation of multiple signal transduction processes. BDNF produced an increase in mitogen‐activated protein (MAP) kinase tyrosine phosphorylation, MAP kinase activity, intracellular calcium concentration and c‐fos expression in the glial cells. Only a subset of the glial cells responded to BDNF, as reflected in single‐cell analysis of calcium transients and c‐fos expression. BDNF had no detectable effect on glial mitotic activity, as measured by DNA synthesis. In parallel studies, nerve growth factor and neurotrophin‐3 had no effect on signalling in these cultures. BDNF has previously been demonstrated to act via trkB receptors with a cytoplasmic tyrosine kinase domain (gp145trkB). Pretreatment of glial cultures with K252a, which at low concentrations specifically inhibits the trk tyrosine kinases, abolished BDNF effects on MAP kinase stimulation, suggesting that BDNF was acting through gp 145trkB. However, subsequent studies showed that gp 145trkB was expressed at extremely low levels in the cultures: gp145trkB mRNA transcripts could only be detected using the reverse transcription‐polymerase chain reaction, and gp 145trkB protein was not detected by either immunoblotting or immunocytochemistry. On the other hand, the glia expressed significantly higher levels of gp95trkB mRNA and protein, which represent truncated forms of trkB receptors lacking the tyrosine kinase domain. The results of these studies demonstrate that a subset of cultured CNS glia respond to BDNF with the activation of conventional signal transduction processes. The mechanism of BDNF‐initiated signal transduction in glial cells most likely involves a relatively small number of gp 145trkB receptors, but involvement of the more abundant truncated gp95trkB receptors cannot be excluded.
Acidic FGF and FGF Receptors are Specifically Expressed in Neurons of Developing and Adult Rat Dorsal Root Ganglia
Authors: Oellig Cornelia , Pirvola Ulla , Taylor Lesley , Elde Robert , Hökfelt Tomas , Pettersson Ralf F. 
Published: April 2006

AbstractEmploying complementary technical approaches, we have studied the expression of acidic fibroblast growth factor (aFGF) and FGF receptors in rat dorsal root ganglia. The results clearly showed that within spinal nerves aFGF and two high‐affinity FGF receptors, FGFR‐1 and FGFRQ, were prominently expressed in neurons, while expression in Schwann cells was undetectable. FGFR‐3 and FGFR‐4 were not expressed in dorsal root ganglia. Acidic FGF mRNA was detected in the majority of dorsal root ganglion neurons, including all size classes; FGFR‐1 and FGFR‐2 transcripts were only detected in subpopulations of mainly large and medium size neurons. In subcellular fractionation studies on dorsal root ganglion and spinal root tissue, aFGF was recovered in the soluble fraction and was thus not tightly associated with neuronal membranes. During development FGFR‐1 and FGFRQ mRNAs were found to be present at all stages examined (embryonic days 15–21 and postnatal days 1–120). Acidic FGF mRNA and protein were first detected at embryonic day 18, and their expression then increased progressively up to postnatal levels. In cultures of dorsal root ganglion neurons derived from day 15 embryos, aFGF expression was first detected 3 days after plating. The resulting neuron cultures continued to express aFGF in a Schwann cell‐independent manner. In combination, these results indicate that aFGF expression in dorsal root ganglia is initiated and maintained in postmitotic neurons. Furthermore, the data suggest that the physiological function of aFGF in the peripheral nervous system is connected to processes specific to the mature sensory (and motor) system, such as the maintenance and survival of peripheral nerve neurons.
The Effect of Barium on [3H]Noradrenalin Release from the Human Neuroblastoma SH‐SY5Y
Authors: Vaughan Peter F. T. , Kaye David F. , Ball Stephen G. , Reeve Helen L. , Peers Chris 
Published: April 2006

AbstractReplacement of Ca2+ with Ba2+ in HEPES‐buffered saline stimulated [3H]noradrenalin release in the human neuroblastoma clone SH‐SY5Y by up to 20% of the cell content in the absence of other secretory stimuli. The Ba2+‐evoked release was inhibited by 85% by 3 μM tetrodotoxin and 95% by 5 μM nifedipine. Ba2+ also increased the potency of K+‐evoked release of [3H]noradrenalin, as maximal release was observed with 60 mM K+ compared with the 100 mM K+ necessary to achieve maximal release in the presence of Ca2+. In contrast, replacing Ca2+ with Ba2+ had little effect on carbachol‐ and bradykinin‐evoked release of [3H]noradrenalin. No evidence was obtained from studies on changes in [Ca2+]i (in response to 100 pM carbachol) using fura‐2 that Ba2+ could enter intracellular stores in SH‐SY5Y cells. Whole‐cell patch‐clamp studies showed that Ba2+ depolarizes SH‐SY5Y cells as well as enhancing inward Ca2+ channel currents and shifting their voltage dependence to more negative values. These results are discussed in terms of the hypothesis that Ba2+ blocks K+ channels, leading to depolarization followed by opening of voltage‐sensitive Na+ channels. This in turn opens voltage‐sensitive L‐type Ca2+ channels, which are coupled to the release of [3H]noradrenalin in SH‐SY5Y cells.