bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of [Ca2+]i Transients in Rat Adrenal Chromaffin Cells by Neuropeptide Y Role for a cGMP‐dependent Protein Kinase‐activated K+ Conductance
Authors: Lemos Virginia Soares , Bucher Bernard , Côrtes Steyner F. , Takeda Kenneth 
Published: April 2006

AbstractThe effects of neuropeptide Y on the intracellular level of Ca2+ ([Ca2+]i) were studied in cultured rat adrenal chromaffin cells loaded with fura‐2. A proportion (16%) of cells exhibited spontaneous rhythmic [Ca2+]i oscillations. In silent cells, oscillations could be induced by forskolin and 1,9–dideoxyforskolin. This action of forskolin was not modified by H‐89, an inhibitor of protein kinase A. Spontaneous [Ca2+i fluctuations and [Ca2+]i fluctuations induced by forskolin‐ and 1,9‐dideoxyforskolin were inhibited by neuropeptide Y. Increases in [Ca2+]i induced by 10 and 20 mM KCI but not by 50 mM KCI were diminished by neuropeptide Y. However, neuropeptide Y had no effect on [Ca2+]i increases evoked by (‐)BAY K8644 and the inhibitory effect of neuropeptide Y on responses induced by 20 mM KCI was not modified by o‐conotoxin GVIA, consistent with neither L‐ nor N‐type voltage‐sensitive Ca2+ channels being affected by neuropeptide Y. Rises in [Ca2+]i provoked by 10 mM tetraethylammonium were not decreased by neuropeptide Y, suggesting that K+ channel blockade reduces the effect of neuropeptide Y. However, [Ca2+]i transients induced by 1 mM tetraethylammonium and charybdotoxin were still inhibited by neuropeptide Y, as were those to 20 mM KCI in the presence of apamin. The actions of neuropeptide Y on [Ca2+]i transients provoked by 20 and 50 mM KCI, 1 mM tetraethylammonium, (‐)BAY K8644 and charybdotoxin were mimicked by 8–bromo‐cGMP. In contrast, 8–bromo‐CAMP did not modify responses to 20 mM KCI or 1 mM tetraethylammonium. The inhibitory effects of neuropeptide Y and 8–bromo‐cGMP on increases in [Ca2+]i induced by 1 mM tetraethylammonium were abolished by the Rp‐8–pCPT‐cGMPS, an inhibitor of protein kinase G, but not by H‐89. A rapid, transient increase in cGMP level was found in rat adrenal medullary tissues stimulated with 1 μM neuropeptide Y. Rises in [Ca2+]i produced by DMPP, a nicotinic agonist, but not by muscarine, were decreased by neuropeptide Y. Our data suggest that neuropeptide Y activates a K+ conductance via a protein kinase G‐dependent pathway, thereby opposing the depolarizing action of K+ channel blocking agents and the associated rise in [Ca2+]i.
PrP and β‐Amyloid Fragments Activate Different Neurotoxic Mechanisms in Cultured Mouse Cells
Authors: Brown David R. , Herms Jochen W. , Schmidt Bernhard , Kretzschmar Hans A. 
Published: April 2006

AbstractAlzheimer's disease and prion diseases such as Creutzfeldt‐Jakob disease are caused by as yet undefined metabolic disturbances of normal cellular proteins, the amyloid precursor protein and the prion protein (PrP). Synthetic fragments of both proteins, β‐amyloid 25–35 (βA25–35) and PrP106–126, have been shown to be toxic to neurons in culture. Cell death in both cases occurs by apoptosis. Here we show that there are considerable differences in the mechanisms involved. Thus, PrP106–126 is not toxic to cortical cell cultures of PrP knockout mouse neurons whereas PA25–35 is. The toxicity of both peptides involves Ca2+ uptake through voltage‐sensitive Ca2+ channels but only PrP106–126 toxicity involves the activity of NMDA receptors. The toxicity of PA25–35, but not PrP106–126, is attenuated by the action of forskolin. These results indicate that PrP106–126 and βA25–35 induce neuronal apoptosis through different mechanisms.
Heparin Inhibits Acetylcholine Receptor Aggregation at Two Distinct Steps in the Agrin‐induced Pathway
Authors: Hopf Carsten , Hoch Werner 
Published: April 2006

AbstractMuscle cells depend on motoneurons for the initiation of postsynaptic differentiation during early development of the neuromuscular junction. Motoneurons secrete specific isoforms of the extracellular matrix protein agrin which trigger the aggregation of acetylcholine receptors (AChRs) on the muscle surface. Both motoneuron‐ and agrin‐induced AChR aggregation are inhibited by heparin. Here we show that this inhibition is due to two separate and distinguishable mechanisms. At high concentrations, heparin directly binds to agrin isoforms which contain the peptide KSRK, resulting in a virtually complete inhibition of AChR clustering. Heparin and other polyanions do not bind to agrin splicing variants without KSRK insert. Isoforms containing or lacking the KSRK insert have a high potency to induce AChR aggregation in the presence of an activating eight‐amino‐acid insert. This activity is inhibited by low concentrations of heparin even in the absence of any binding of heparin to agrin. Therefore, this second type of inhibition is due to the interaction of heparin with a downstream component of the agrin‐induced clustering pathway. Binding of heparin to this yet unidentified component substantially decreases, but does not completely abolish AChR aggregation. The inhibition is particularly strong on myotubes which have not completely matured in culture.
Induction of Adhesion/Differentiation of Human Neuroblastoma Cells by Tumour Necrosis Factor‐α Requires the Expression of an Inducible Nitric Oxide Synthase
Authors: Obregón Eva , Punzón M. Carmen , González‐Nicolás Josefa , Fernández‐Cruz Eduardo , Fresno Manuel , Muñoz‐Fernández M. Angeles 
Published: April 2006

AbstractNeuroblastoma cell lines (SK‐N‐SH and SK‐N‐MC) were induced to differentiate, as detected by the expression of neurofilament proteins of 68 and 200 kDa, and to express adhesion molecules (intercellular adhesion molecule‐1 and vascular cell adhesion molecule) after stimulation with tumour necrosis factor‐α (TNF‐α). This induction was accompanied by the arrest of cell growth. The induction of neuroblastoma adhesion by TNF‐α could be inhibited by the nitric oxide synthase inhibitors, L‐N‐monomethyl arginine (L‐NMMA) andL‐N6‐(1–imidoethyl)‐lysine (highly specific for the inducible enzyme), but not by the inactive enantiomer D‐NMMA. These results indicate that TNF‐α induces the adhesion of neuroblastoma cells via nitric oxide. This was confirmed by the finding that the adhesion/differentiation of SK‐N‐SH and SK‐N‐MC cells can be directly induced by the addition of nitric oxide donors, sodium nitroprusside and S‐nitroso‐N‐acetyl‐penicillamine, into the culture medium. The isoform of the nitric oxide synthase induced in human neuroblastoma cells by TNF‐α treatment was identified enzymatically as isoform II by Western blotting and by the polymerase chain reaction. Thus TNF‐α induces the in vitro adhesion/differentiation of human neuroblastoma cells through nitric oxide synthesized by a calcium‐independent inducible form of nitric oxide synthase, clearly indicating that isoform II of nitric oxide synthase can be expressed in human neuronal cell types.
Localization of Neuropeptide Y Y1 mRNA in the Human Brain: Abundant Expression in Cerebral Cortex and Striatum
Authors: Caberlotto Laura , Fuxe Kjell , Sedvall Göran , Hurd Yasmin L. 
Published: April 2006

AbstractMany neurobiological functions have been ascribed to the NPY Y1 receptor subtype, but autoradiographic analysis has failed to detect Y1 binding sites in most human brain areas, in contrast to the rat. We examined the regional distribution of Y1 mRNA‐containing cells in the post‐mortem human brain to clarify if there is a major species difference in terms of the existence of Y1 receptors in the human telencephalon, in particular the striatum and cortex. In situ hybridization experiments revealed widespread distribution of Y1 mRNA signals in all layers of most limbic and neocortical regions, predominantly in layer IV (most cortical regions) and layer VI. The striatum showed moderate Y1 receptor mRNA expression levels with intensely expressing cells localized to the nucleus accumbens. The highest Y1 receptor mRNA expression was apparent within the dentate gyrus, and the lowest in the subiculum, parahippocampal gyrus, cerebellum, and thalamus. In vitro autoradiography using [125I]Leu31Pro34‐PYY and [125I]PYY with NPY (13–36) or Leu31 Pro34 NPY; confirmed the presence of low Y1–like binding in the human brain despite abundant Y1 mRNA expression. However, using a rat model of the human autopsy process, it was apparent that the inability to reveal high Y1– versus Y2–like receptors in the human brain was related in part to marked reductions of Y1–like, but not Y2–like, receptors within a 4 h post‐mortem delay. Altogether, the results indicate that the Y1 receptor gene is abundant in the human brain and this receptor may have important roles in cognitive, limbic and motor function.
Neuronal and Glial Glutamate Transporters Possess an SH‐based Redox Regulatory Mechanism
Authors: Trotti Davide , Rizzini Barbara Lodi , Rossi Daniela , Haugeto Oyvind , Racagni Giorgio , Danbolt Niels C. , Volterra Andrea 
Published: April 2006

AbstractGlutamate uptake into nerve cells and astrocytes via high‐affinity transporters controls the extracellular glutamate concentration in the brain, with major implications for physiological excitatory neurotransmission and the prevention of excitotoxicity. We report here that three recently cloned rat glutamate transporter subtypes, viz. EAAC1 (neuronal), GLT1 and GLAST (glial), possess a redox‐sensing property, undergoing opposite functional changes in response to oxidation or reduction of reactive sulphydryls present in their structure. In particular, thiol oxidation with 5,5′‐dithio‐bis(2–nitrobenzoic) acid (DTNB) and disulphide reduction with dithiothreitol (DTT) result, respectively, in reduced and increased uptake capacity by a preparation of partially purified brain transporters as well as by the three recombinant proteins reconstituted into liposomes. In this model system, EAAC1, GLT1 and GLAST react similarly to DTT/DTNB exposures despite their different contents of cysteines, suggesting that only the conserved residues might be involved in redox modulation. Redox sensitivity is a property of the glutamate transporters also when present in their native cell environment. Thus, by using cultured cortical astrocytes and the whole‐cell patch‐clamp technique we were able to observe dynamic increase and decrease of the glutamate uptake current in response to application of DTT and DTNB in sequence. Moreover, in the same paradigm, DDT‐reversible current inhibition was observed with hydrogen peroxide instead of DTNB, indicating that the SH‐based redox modulatory site is targeted by endogenous oxidants and might constitute an important physiological or pathophysiological regulatory mechanism of glutamate uptake in vivo
Leukaemia Inhibitory Factor is Retrogradely Transported by a Distinct Population of Adult Rat Sensory Neurons: C‐o‐localization with trkA and other Neurochemical Markers
Authors: Thompson Stephen W. N. , Vernallis Ann B. , Heath John K , Priestley John V. 
Published: April 2006

AbstractSciatic sensory afferents that retrogradely transport and accumulate leukaemia inhibitory factor (LIF) within their soma were characterized in the adult rat in vivo. Twenty‐four percent of neurons within the L4 and L5 dorsal root ganglia accumulated biotinylated LIF following intraneural injection of the cytokine into the sciatic nerve. Labelled cell bodies were predominantly of small diameter (20.1 ± 2 0.5 μm). Retrograde transport was eliminated by excess unlabelled LIF but not by the related cytokines, ciliary‐derived neurotrophic factor (CNTF) and interleukin‐6 (IL‐6). Double labelling revealed that the majority (81%) of LIF‐accumulating neurons were immunopositive for CGRP and 34% were immunopositive for the cell surface glycoconjugate IB4. Sixty‐two percent of LIF‐accumulating neurons were immunopositive for trkA. Our results demonstrate a group of small‐diameter sensory neurons that retrogradely transport LIF, comprising cells that constitutively express neuropeptides and those likely to be peptide‐deficient. LIF‐accumulating neurons expressing trkA are also potentially responsive to nerve growth factor. It is likely that the LIF‐accumulating neurons described in this study are nociceptive in function.
Role of the Dorso—Caudal Neostriatum in Filial Imprinting of the Domestic Chick: a Pharmacological and Autoradiographical Approach Focused on the Involvement of NMDA‐Receptors
Authors: Bock Jörg , Schnabel Reinhild , Braun Katharina 
Published: April 2006

AbstractNewly hatched domestic chicks were either acoustically imprinted on 400 Hz tone pulses or visually imprinted on a rotating red light. Compared to naive control animals, both groups of imprinted chicks expressed significantly enhanced stimulus evoked 2‐fluoro‐2‐deoxyglucose (2‐FDG) uptake in circumscribed areas of the dorso‐caudal neostriatum (Ndc). This enhanced excitability after imprinting seems not to be related to changes of NMDA‐receptor densities as measured by quantitative receptor autoradiography. However, pharmacological blockade of NMDA‐receptors in the dorso‐caudal neostriatum leads to a marked suppression of stimulus‐evoked 2‐FDG uptake in the dorso‐caudal neostriatum and also in the interconnected imprinting relevant forebrain area, medio‐rostral neostriatum/hyperstriatum ventrale (MNH). Furthermore, chicks which received bilateral Ndc injections of the competitive NMDA antagonist DL‐2‐amino‐5‐phosphono valeric acid (APV) during the imprinting experiments showed a dose‐dependent decrease of imprinting success compared to vehicle‐injected controls. These results indicate that the dorso‐caudal neostriatum may represent a polysensory associative brain region in which visual and acoustic features of imprinting objects may be integrated. The activation in this area evoked by the imprinting stimulus during and after imprinting is critically dependent on NMDA‐receptor activation, which appears to be required for this learning process.
Na+—Ca2+ Exchange Currents in Cortical Neurons: Concomitant Forward and Reverse Operation and Effect of Glutamate
Authors: Yu Shan Ping , Choi Dennis W. 
Published: April 2006

AbstractNa+‐Ca2+ exchanger‐associated membrane currents were studied in cultured murine neocortical neurons, using whole‐cell recording combined with intracellular perfusion. A net inward current specifically associated with forward (Na+o‐Ca2+i) exchange was evoked at ‐40 mV by switching external 140 mM Li+ to 140 mM Na+. The voltage dependence of this current was consistent with that predicted for 3Na+:1Ca2+ exchange. As expected, the current depended on internal Ca2+, and could be blocked by intracellular application of the exchanger inhibitory peptide, XIP. Raising internal Na+ from 3 to 20 mM or switching the external solution from 140 mM Li+ to 30 mM Na+ activated outward currents, consistent with reverse (Na+,‐Ca2+o) exchange. An external Ca2+‐sensitive current was also identified as associated with reverse Na+‐Ca2+ exchange based on its internal Na+ dependence and sensitivity to XIP. Combined application of external Na+ and Ca2+ in the absence of internal Na+ triggered a 3.3–fold larger inward current than the current activated in the presence of 3 mM internal Na+, raising the intriguing possibility that Na+‐Ca2+ exchangers might concurrently operate in both the forward and the reverse direction, perhaps in different subcellular locations. With this idea in mind, we examined the effect of excitotoxic glutamate receptor activation on exchanger operation. After 3–5 min of exposure to 100–200 μM glutamate, the forward exchanger current was significantly increased even when external Na+ was reduced to 100 mM, and the external Ca2+‐activated reverse exchanger current was eliminated.
FGF‐2 Induces Nerve Growth Factor Expression in Cultured Rat Hippocampal Neurons
Authors: Ferhat Lotfi , Represa Alfonso , Zouaoui‐Aggoun Djamila , Ferhat Walid , Ben‐Ari Yezekiel , Khrestchatisky Michel 
Published: April 2006

AbstractBasic fibroblast growth factor (FGF‐2) is expressed in the hippocampus and has been demonstrated to promote neurotrophic effects on hippocampal neurons in vifro. We show that these neurons, even at the embryonic stage, express the mRNAs encoding the FGF receptors, bek and flg. We have characterized the effects of FGF‐2 on the expression of nerve growth factor (NGF) using the reverse transcription‐coupled polymerase chain reaction, in situ hybridization and immunocytochemistry. In hippocampal neurons grown in the absence of serum, FGFB exposure induces an important elevation of NGF mRNA expression followed by a marked increase in NGF immunoreactivity. Combining in situ hybridization with an NGF probe and microtubule‐associated protein‐2 (MAP2) immunocytochemistry we show that the induction of NGF mRNA by FGF‐2 is localized in MAP2–immunoreactive neurons. These results suggest roles for FGF‐2 in the development of hippocampal neurons and in the maintenance of connections in the central nervous system, particularly the septo‐hippocampal pathway, via the regulation of an important neurotrophins
192 IgG—Saporin‐induced Loss of Cholinergic Neurons in the Septum Abolishes Cholinergic Sprouting After Unilateral Entorhinal Lesion in the Rat
Authors: Naumann Thomas , Deller Thomas , Bender Roland , Frotscher Michael 
Published: April 2006

AbstractAfter unilateral lesion of the entorhinal cortex, cholinergic septohippocampal fibres are believed to sprout in the denervated outer molecular layer of the rat dentate gyrus. This cholinergic sprouting has been demonstrated by acetylcholinesterase (AChE) histochemistry, a method said selectively to label cholinergic septohippocampal fibres in the hippocampus. However, a recent report has questioned this concept, suggesting that AChE may not be an adequate marker to monitor cholinergic sprouting and that other, non‐cholinergic axons sprouting after entorhinal cortex lesion cause the dense AChE‐positive band in the denervated outer molecular layer. In order to determine the contribution of cholinergic septohippocampal fibres to the dense AChE band appearing after entorhinal cortex lesion, the neurotoxin 192 IgG‐saporin, known to destroy cholinergic neurons in the basal forebrain selectively, was used. Rats received bilateral injections of 192 IgG‐saporin into the lateral ventricles 3 weeks before entorhinal cortex lesion, simultaneously with entorhinal cortex lesion, or 8 weeks after entorhinal cortex lesion. lmmunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrated the loss of cholinergic neurons in the medial septum and diagonal band after 192 IgG‐saporin treatment. The cholinergic sprouting response in the molecular layer, as visualized with AChE histochemistry, was abolished in all animals treated with immunotoxin. These data indicate that the dense AChE band forming after entorhinal cortex lesion represents the sprouting of cholinergic septohippocampal fibres.
A Metabolic Mapping Study of Orientation Discrimination and Detection Tasks in the Cat
Authors: Vanduffel Wim , Vandenbussche Erik , Singer Wolf , Orban Guy A. 
Published: April 2006

AbstractIncreasing evidence suggests that a large number of distinct cortical areas and associated subcortical structures participate in the processing of visual information and that different aspects of visual scenes are evaluated in different areas. This necessitates identification of cortical and subcortical regions cooperating in particular visual tasks. Using the 2‐deoxyglucose technique, we monitored the differential activation of areas in the cat visual cortex participating in an orientation discrimination and a detection task. Concordant with previous lesion studies, we found increased activity levels in area 17 in the discrimination condition relative to the detection condition. In addition, the 2‐deoxyglucose technique revealed discrimination‐related increased activations in the claustrum, the putamen and in parts of the anteromedial, anterolateral and posterolateral lateral suprasylvian visual areas. Regions activated differentially with the detection task comprised subdivisions of areas 17, 18, 19 and 21, posterior area 7 (7p), several areas of the posterior part of the middle and posterior suprasylvian sulcus, the pulvinar complex and the superior colliculus. These results show that the 2‐deoxyglucose technique is useful to investigate cognitive brain functions, and that different sets of cortical and subcortical regions are activated during two visual tasks with similar visual stimulation.
The Functional Organization of Working Memory Processes Within Human Lateral Frontal Cortex: The Contribution of Functional Neuroimaging
Authors: Owen Adrian M. 
Published: April 2006

AbstractRecent functional neuroimaging studies have provided a wealth of new information about the likely organization of working memory processes within the human lateral frontal cprtex. This article seeks to evaluate the results of these studies in the context of two contrasting theoretical models of lateral frontal‐lobe function, developed through lesion and electrophysiological recording work in non‐human primates (Goldman‐Rakic, 1994, 1995; Petrides, 1994, 1995). Both models focus on a broadly similar distinction between anatomically and cytoarchitectonically distinct dorsolateral and ventrolateral frontal cortical areas, but differ in the precise functions ascribed to those regions. Following a review of the relevant anatomical data, the origins of these two theoretical positions are considered in some detail and the main predictions arising from each are identified. Recent functional neuroimaging studies of working memory processes are then critically reviewed in order to assess the extent to which they support either, or both, sets of predictions. The results of this meta‐analysis suggest that lateral regions of the frontal lobe are not functionally organized according to stimulus modality, as has been widely assumed, but that specific regions within the dorsolateral or ventrolateral frontal cortex make identical functional contributions to both spatial and non‐spatial working memory.
Type 2 Metabotropic Glutamate (mGlu) Receptors Tonically Inhibit Transmitter Release in Rat Caudate Nucleus: In Vivo Studies with (2S,1′S,2′S,3′R)‐2‐(2′‐carboxy‐3′‐phenylcyclopropyl)glycine, a New Potent and Selective Antagonist
Authors: Cozzi Andrea , Attucci Sabina , Peruginelli Fiamma , Marinozzi Maura , Luneia Roberto , Pellicciari Roberto , Moroni Flavio 
Published: April 2006

AbstractAnatomical, biochemical and electrophysiological studies have previously shown that cortico‐striatal terminals contain abundant presynaptic group 2 metabotropic glutamate (mGlu) receptors. Using brain slices we have previously shown that these receptors inhibit depolarization‐induced transmitter release. Using microdialysis in freely moving rats, we now report the effects of group 2 mGlu receptor agonists and antagonists on glutamate concentration in the caudate extracellular fluid. A mild decrease (20–30%) in glutamate concentration in caudate dialysates was observed when 1S,3R‐1‐aminocyclopentane‐1,3‐dicarboxylic acid or (2S,3S,4S)‐α‐carboxycyclopropyl‐glycine (L‐CCG‐1), mGlu receptor agonists, was locally administered. On the contrary, α‐methyl‐4‐carboxyphenylglycine, an antagonist of type 1 and type 2 mGlu receptors, increased the glutamate concentration in dialysates by up to 3.5‐fold, and its effects were prevented by the simultaneous administration of L‐CCG‐1, a preferential type 2 mGlu receptor agonist. A significant increase of glutamate output in striatal dialysate was also found after local administration of (2S,1′S,2′S,3′R)‐2‐(2′‐carboxy‐3′‐phenylcyclopropyl)glycine, another structurally unrelated, relatively selective and potent type 2 mGlu receptor antagonist. The results suggest that type 2 mGlu receptors tonically inhibit transmitter release from corticostriatal terminals. Since the cortico‐striatal pathway profoundly affects the function of a large percentage of caudate neurons, it is reasonable to predict that the use of selective type 2 mGlu receptor agents will be helpful for scientific and therapeutic studies on the physiopathology of basal ganglion disorders.