bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel pluripotential neural progenitor lines exhibiting rapid controlled differentiation to neurotransmitter receptor‐expressing neurons and glia
Authors: Jung Marion , Krämer Eva‐Maria , Müller Thomas , Antonicek Horst , Trotter Jacqueline 
Published: March 2003

AbstractThe immortalization of progenitor cells from embryonic murine hippocampus using oncogene‐carrying retroviral vectors is described. Use of a vector encoding the oncogene v‐myc results in lines of nestin‐positive progenitor cells. Limited differentiation ensues if the cells are cultured in the presence of dibutyryl cyclic adenosine monophosphate. In contrast, use of a vector in which the extracellular portion of the epidermal growth factor (EGF) receptor is fused to the neu tyrosine kinase generates lines of pluripotential nestin‐positive progenitor cells, which differentiate upon withdrawal of EGF into neurons and glia. Differentiated neurons expressing action potentials and neurotransmitter receptors make up a high proportion of the cells. These cell lines are useful tools to investigate the characteristics of differentiating neurons and glia, as well as to screen neuroactive drugs. This work has been reported in preliminary form as an abstract (1996 Society for Neuroscience Abstract, #606.20, p. 1537).
Attenuation of 6‐OHDA‐induced neurotoxicity in glutathione peroxidase transgenic mice
Authors: Bensadoun J. C. , Mirochnitchenko O. , Inouye M. , Aebischer P. , Zurn A. D. 
Published: March 2003

AbstractNormal cellular metabolism produces oxidants which are neutralized within cells by antioxidant enzymes and other antioxidants. An imbalance between oxidants and antioxidants has been postulated to lead to the degeneration of specific populations of neurons in neurodegenerative diseases, e.g. Parkinson's disease. The present study investigates whether overexpression of glutathione peroxidase, the enzyme which metabolizes hydrogen peroxide to water, can prevent or slow down neuronal injury in an animal model of Parkinson's disease. Transgenic mice overexpressing the human glutathione peroxidase gene under the control of the mouse hydroxymethylglutaryl‐coenzyme A promoter and genetically matched control mice were injected intracerebroventricularly with the dopaminergic neurotoxin 6‐hydroxydopamine. Seven days after injection, the number of tyrosine hydroxylase‐positive nigral dopaminergic neurons was decreased by 52.4% and 20.5% in 6‐hydroxydopamine‐injected control and glutathione peroxidase transgenic mice, respectively. Similarly, 3 days after injection of the neurotoxin, striatal dopamine was decreased by 71.2% and 56.5%, respectively. Overexpression of glutathione peroxidase therefore partially protects dopaminergic neurons against 6‐hydroxydopamine‐induced toxicity.
Differential time course of neuronal and glial apoptosis in neonatal rat dorsal root ganglia after sciatic nerve axotomy
Authors: Whiteside G. , Doyle C. A. , Hunt S. P. , Munglani R. 
Published: March 2003

AbstractSensory neurons in neonatal rat lumbar dorsal root ganglia die after sciatic nerve axotomy, and previous studies have estimated the total cell loss to be 40–95%. We have used the terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labelling (TUNEL) technique, combined with immunohistochemistry, to investigate the contribution of apoptosis to the cell loss that occurs after unilaterally transecting the sciatic nerve of new‐born rats.  TUNEL‐positive cells were detected 1 day post‐lesion, and their number peaked 3 days after the injury. Combining TUNEL labelling with immunohistochemistry, for neuron‐specific neurofilament 150 kDa, or glial‐specific S‐100β, enabled us to identify dying neurons and dying glia. One day after axotomy, most of the TUNEL‐positive cells (58%) were neurons, whereas 3 days post‐injury, only a small number of dying cells (6%) were neuronal. This lower incidence was due to a decrease in neuronal death and an increase in glial death. The glia in the dorsal root ganglia therefore die subsequent to the neurons. The apoptotic nature of the cell death was confirmed by electron microscopy, with fine structural features of apoptotic cell death, e.g. chromatin compaction and membrane blebbing, being observed in both glia and neurons.  Our results confirm that extensive apoptosis occurs in the neonatal lumbar dorsal root ganglia after sciatic nerve section, and show that neurons and glial cells die with different time‐courses. The results suggest a neuron‐glia trophic interdependence in the dorsal root ganglia.
Regional and differential expression of gelatinases in rat brain after systemic kainic acid or bicuculline administration
Authors: Zhang J. Wenjun , Deb Suman , Gottschall Paul E. 
Published: March 2003

AbstractIndirect evidence from in vitro studies implicates a functional role for matrix metalloproteinases (MMPs) in the central nervous system (CNS), including induction of neuronal migration during development and enhancement of neurite extension. Few reports have documented the expression of these enzymes in the brain, especially after injury in vivo. The objective of this study was to determine whether MMPs are expressed in various regional areas of rat brain after administration of the neurotoxin, kainic acid. Limbic motor seizures and neuronal degeneration were induced in Sprague–Dawley rats by systemic administration of kainate (10 mg/kg). Rats were subsequently divided into convulsive and non‐convulsive groups, after observing their behaviour in response to the drug. Animals were killed 6, 12, 24, 72 and 168 h (7 days) after injection of kainate. Gelatinases were extracted from various brain regions and assayed by gelatin‐substrate zymography. Levels of glial fibrillary acidic protein (GFAP) in corresponding regions were measured by ELISA. In the absence of treatment, MMP‐2 and MMP‐9 activities were expressed differentially in various brain regions with the highest levels in the hippocampus and the lowest in the cerebellum. In areas from convulsive rats, MMP‐9 activity was markedly elevated at 6 h, and reached a maximum at 12 h after injection of kainate (8.1‐fold hippocampus, 7.7‐fold diencephalon, 7.2‐fold striatum, 5.7‐fold frontal cortex, 5.5‐fold cerebellum, 2.6‐fold midbrain). MMP‐2 activity was induced more than two‐fold in the hippocampus, diencephalon and striatum, to a lesser extent in the frontal cortex and midbrain, and was unchanged in the cerebellum, 72 h after injection. Neither MMP activity was altered in any brain region derived from non‐convulsive rats. Treatment with the GABAA antagonist, bicuculline, resulted in increased levels of MMP‐9, 12 h after drug administration, but no change in levels of MMP‐2 up to 3 days following treatment. GFAP levels were induced 3 days after kainic acid injection in brain regions where MMP‐2 was elevated. Nissl staining displayed the classical, regional neurodegeneration in kainate‐treated animals that exhibited seizures. No obvious degeneration was detected in kainate‐treated, non‐convulsive rats or bicuculline‐treated animals. These data demonstrate that MMP‐9 and MMP‐2 are differentially expressed with respect to time after kainic acid injection, and suggest that they are regulated by convulsion and/or neurodegenerative‐associated mechanisms, respectively. Although similar in catalytic activity, MMP‐9 and MMP‐2 may play different roles in response to kainic acid‐induced seizure and neuronal degeneration.
European Neuroscience Association Pre‐ and post‐synaptic muscarinic receptors in thin slices of rat adrenal gland
Authors: Barbara Jean‐Gaël , Lemos Virginia Soares , Takeda Kenneth 
Published: March 2003

AbstractThe effects of activation of muscarinic receptors on chromaffin cells and splanchnic nerve terminals were studied in a rat adrenal slice preparation. In chromaffin cells, muscarine induced a transient hyperpolarization followed by a depolarization associated with cell spiking. The hyperpolarization was blocked by charybdotoxin (1 μm) and tetraethylammonium chloride (TEA, 1 mm), but was not affected by 200 μm Cd2+ or removal of external Ca2+, consistent with activation of BK channels. This would follow internal Ca2+ mobilization, as shown by Ca2+ imaging with fura‐2 on isolated chromaffin cells in culture. Under voltage‐clamp, outward BK currents were insensitive to MT3 toxin, a specific muscarinic m4 receptor antagonist. In contrast, muscarine‐induced depolarization was due to a m4 receptor‐mediated inward current blocked by MT3 toxin. This current was permeable to cations and was associated with Ca2+ entry and subsequently, Ca2+‐induced Ca2+ release. Finally, both muscarine (25 μm) and oxotremorine (10 μm) decreased the amplitude and frequency of KCl‐evoked excitatory postsynaptic currents, without affecting quantal size, consistent with a presynaptic inhibitory effect. Taken together, our data suggest that activation of m4 and probably m3 muscarinic receptors results in a strong, long‐lasting excitation of chromaffin cells, as well as an uncoupling of synaptic inputs onto these cells.
Molecular cloning and characterization of an invertebrate homologue of a neuropeptide Y receptor
Authors: Tensen Cornelis P. , Cox Kingsley J. A. , Burke Julian F. , Leurs Rob , Van Der Schors Roel C. , Geraerts Wijnand P. M. , Vreugdenhil Erno , Van Heerikhuizen Harm 
Published: March 2003

AbstractNeuropeptide Y is an abundant and physiologically important peptide in vertebrates having effects on food intake, sexual behaviour, blood pressure and circadian rhythms. Neuropeptide Y homologues have been found in invertebrates, where they are very likely to play similar, important roles. Although five neuropeptide Y‐receptor subtypes have been identified in mammals, none has been reported from invertebrates. Here we describe the cloning of a neuropeptide Y‐receptor from the brain of the snail Lymnaea stagnalis. The identity of the receptor was deduced by expressing the neuropeptide Y‐receptor‐encoding cDNA in Chinese Hamster Ovary cells, which were subsequently challenged with size‐fractionated Lymnaea brain extracts. An active peptide, selected on the basis of its ability to induce changes in cAMP levels, was purified to homogeneity, analysed by mass spectrometry and amino acid sequence determination, and turned out to be a Lymnaea homologue of neuropeptide Y.
Involvement of GABAB receptors in convulsant‐induced epileptiform activity in rat neocortex in vitro
Authors: Sutor Bernd , Luhmann Heiko J. 
Published: March 2003

AbstractThe role of γ‐aminobutyric acid B (GABAB) receptors in the generation and maintenance of bicuculline‐induced epileptiform activity in rat neocortical slices was studied using electrophysiological methods. A block of GABAB receptors in the presence of functional GABAA receptor‐mediated inhibition was not sufficient to induce epileptiform activity. In the presence of the GABAA receptor antagonist bicuculline (10 μm) and at suprathreshold stimulation, the GABAB receptor antagonist CGP 35348 (10–300 μm) significantly potentiated epileptiform activity. With stimulation at threshold intensity, low concentrations of CGP 35348 (10–30 μm) potentiated bicuculline‐induced activity, whereas higher concentrations (100–300 μm) invariably led to a reversible suppression of stimulus‐evoked epileptiform discharges. CGP 35348 also enhanced picrotoxin‐induced epileptiform activity, but at higher concentrations it was considerably less effective in suppressing such epileptiform discharges. The GABA uptake inhibitor nipecotic acid partially mimicked the actions of CGP 35348: with stimulation at threshold intensity, it reversibly suppressed bicuculline‐induced epileptiform field potentials, but it did not influence epileptiform activity induced by picrotoxin. We conclude that a postsynaptic blockade of GABAB receptors induces an amplification of epileptiform activity in neocortical slices disinhibited by GABAA receptor antagonists. An additional blockade of presynaptic GABAB receptors, especially under conditions of weak stimulation of the neurons, reduces the inhibitory auto‐feedback control of GABA release, leading to a displacement of competitive antagonists from the postsynaptic GABAA receptor and hence, to a suppression of epileptiform activity induced by competitive GABAA receptor antagonists.
Corticotrophin‐releasing factor produces a long‐lasting enhancement of synaptic efficacy in the hippocampus
Authors: Wang H. L. , Wayner M. J. , Chai C. Y. , Lee E. H. Y. 
Published: March 2003

AbstractWe have previously demonstrated that intra‐hippocampal injection of corticotrophin‐releasing factor improved memory retention of an inhibitory avoidance learning in rats; while the electrophysiological effects corticotrophin‐releasing factor produces on hippocampal neurons are largely uncharacterized. In the present study, we found that corticotrophin‐releasing factor injected into the dentate gyrus of hippocampus produced a dose‐dependent and long‐lasting enhancement in synaptic efficacy of these neurons, as measured by an increase in the amplitude and slope of population excitatory postsynaptic potentials, as well as the amplitude of population spike. The onset of corticotrophin‐releasing factor‐induced potentiation was slow. It was observed approximately 40–60 min after corticotrophin‐releasing factor administration and lasted for more than 5 h. This effect of corticotrophin‐releasing factor was blocked by pretreatment with the cyclase‐adenosine‐3,5‐monophosphate (cAMP) inhibitor Rp‐adenosine‐3,5‐cyclic monophosphothiolate triethylamine (Rp‐cAMPS) and partially blocked by the N‐methyl‐D‐aspartate receptor antagonist MK‐801. Further, pretreatment with corticotrophin‐releasing factor receptor antagonist dose‐dependently diminished tetanization‐induced long‐term potentiation, and corticotrophin‐releasing factor and tetanic stimuli had an additive effect on hippocampal neuron excitation. Moreover, direct injection of corticotrophin‐releasing factor increased cAMP level in the dentate gyrus. These results together suggest that corticotrophin‐releasing factor‐induced potentiation simulates the late phase of tetanization‐induced long‐term potentiation and cAMP seems to be the messenger mediating this effect. Moreover, corticotrophin‐releasing factor‐induced potentiation and long‐term potentiation may share some similar mechanisms, and corticotrophin‐releasing factor is probably involved in the neural circuits underlying long‐term potentiation. Thus, corticotrophin‐releasing factor may play an important role in modulating synaptic plasticity in the hippocampus.
Effect of GABA on the processing of interaural time differences in nucleus laminaris neurons in the chick
Authors: Brückner Susanne , Hyson Richard L. 
Published: March 2003

AbstractNeurons in the avian nucleus laminaris (NL) are the first to receive binaural information and are presumed to play a role in encoding interaural time differences (ITD). NL not only receives excitatory projections from the ipsi‐and contralateral nucleus magnocellularis, but also receives inhibitory (GABAergic) input. This study investigates how GABA (γ‐aminobutyric acid) influences ITD coding in NL.  Intracellular responses of chick NL neurons were studied in a brain slice preparation. Both excitatory inputs to NL were electrically activated and the delay between trains of bilateral stimuli (simulated‐interaural time difference [s‐ITD]) was varied. The resulting s‐ITD functions were recorded in the presence of 0–75 μm GABA.  The discharge rate of NL neurons varied with s‐ITD. Cells responded maximally using s‐ITDs at which the peak of the ipsi‐ and contralateral excitatory postsynaptic potentials occurred simultaneously (favourable s‐ITD). At unfavourable s‐ITDs, the discharge rates usually fell below unilateral levels.  GABA had contrary effects on the s‐ITD functions depending on the drug concentration. A low GABA dose enhanced excitability at favourable s‐ITD, but not at unfavourable s‐ITDs. In contrast, higher GABA concentrations diminished excitability. Moderate GABA concentrations had no consistent effect.  These results suggest that the GABAergic input to NL will either increase or decrease the excitability of the NL neuron depending on the degree to which this GABAergic input is activated. A gain control hypothesis is presented in which the GABAergic input makes ITD processing in NL independent of the stimulus intensity by adjusting the excitability of NL neurons.
P2X3 is expressed by DRG neurons that terminate in inner lamina II
Authors: Vulchanova L. , Riedl M. S. , Shuster S. J. , Stone L. S. , Hargreaves K. M. , Buell G. , Surprenant A. , North R. A. , Elde R. 
Published: March 2003

AbstractThe P2X3 receptor subunit, a member of the P2X family of ATP‐gated ion channels, is almost exclusively localized in sensory neurons. In the present study, we sought to gain insight into the role of P2X3 and P2X3‐containing neurons in sensory transmission, using immunohistochemical approaches. In rat dorsal root ganglia (DRG), P2X3‐immunoreactivity (‐ir) was observed in small‐ and medium‐sized neurons. Approximately 40% of DRG neuronal profiles in normal rats contained P2X3‐ir. In rats that had received neonatal capsaicin treatment, the number of P2X3‐positive neurons was decreased by approximately 70%. Analysis of the colocalization of P2X3‐ir with cytochemical markers of DRG neurons indicated that approximately 94% of the P2X3‐positive neuronal profiles were labelled by isolectin B4 from Bandeiraea simplicifolia, while only 3% contained substance P‐ir, and 7% contained somatostatin‐ir. In dorsal horn of rat spinal cord, P2X3‐ir was observed in the inner portion of lamina II and was reduced subsequent to dorsal rhizotomy, as well as subsequent to neonatal capsaicin treatment. Finally, P2X3‐ir accumulated proximal to the site of sciatic nerve ligation, and was seen in nerve fibres in skin and corneal epithelium. In summary, our results suggest that P2X3 is expressed by a functionally heterogeneous population of BSI‐B4‐binding sensory neurons, and is transported into both central and peripheral processes of these neurons.
AMPA receptor subunits are differentially expressed in parvalbumin‐ and calretinin‐positive neurons of the rat hippocampus
Authors: Catania Maria Vincenza , Bellomo Maria , Giuffrida Raffaella , Giuffrida Rosario , Stella Anna Maria Giuffrida , Albanese Vincenzo 
Published: March 2003

AbstractRecent studies suggest a functional diversity of native α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate‐type glutamate receptor channels (AMPARs). In several types of interneurons, AMPARs are characterized by higher Ca2+ permeability and faster kinetics than AMPARs in principal cells. We studied the expression profile of AMPAR subunits in the hippocampal parvalbumin (PV)‐ and calretinin (CR)‐positive cells, which represent different populations of non‐principal cells. To this end, non‐radioactive in situ hybridization with AMPAR subunit specific cRNAs was combined with immunocytochemistry for PV or CR. Double‐immunolabelling using antibodies against AMPAR subunits and PV or CR was also performed. PV‐containing neurons represent a fairly homogeneous population of cells expressing high levels of GluR‐A and GluR‐D mRNAs, moderate levels of GluR‐C and low levels of GluR‐B mRNAs in all the examined regions of hippocampus. The vast majority of CR‐containing cells have a much lower expression of GluR‐A, ‐C and ‐D mRNA than PV‐positive neurons, although similarly featuring low levels of GluR‐B mRNA. Only a subpopulation of CR‐containing cells, the spiny neurons of the dentate gyrus and CA3 region of the hippocampus were characterized by a strong expression of GluR‐A and ‐D subunit mRNAs. The differential pattern found for the AMPAR subunit mRNA expression was confirmed by immunocytochemistry at protein level. Despite the common feature of low GluR‐B subunit expression, PV‐ and CR‐containing interneurons differ with respect to the density and combination of their expressed AMPAR subunits. The different combination of subunits might subserve different properties of the AMPA channels featured by these cell types, with implications for the functioning of the hippocampal network.
Dopaminergic modulation of early signs of excitotoxicity in visualized rat neostriatal neurons
Authors: Cepeda Carlos , Colwell Christopher S. , Itri Jason N. , Gruen Ehud , Levine Michael S. 
Published: March 2003

AbstractCell swelling induced by activation of excitatory amino acid receptors is presumably the first step in a toxic cascade that may ultimately lead to cell death. Previously we showed that bath application of N‐methyl‐d‐aspartate (NMDA) or kainate (KA) produces swelling of neostriatal cells. The present experiments examined modulation of NMDA and KA‐induced cell swelling by dopamine (DA) and its receptor agonists. Nomarski optics and infra‐red videomicroscopy were utilized to visualize neostriatal medium‐sized neurons in thick slices from rat pups (12–18 postnatal days). Increase in somatic cross‐sectional area served as the indicator of swelling induced by bath application of glutamate receptor agonists. NMDA induced cell swelling in a dose‐dependent manner. Activation of DA receptors in the absence of NMDA did not produce swelling. DA and the D1 receptor agonist SKF 38393, increased the magnitude of swelling produced by NMDA. This effect was reduced in the presence of the D1 receptor antagonist, SCH 23390. In contrast, activation of D2 receptors by quinpirole decreased the magnitude of NMDA‐induced cell swelling. DA slightly attenuated cell swelling induced by activation of KA receptors. Quinpirole produced a significant concentration‐dependent reduction in KA‐induced swelling while SKF38393 increased KA‐induced swelling, but only at a low concentration of KA. Together, these results provide additional support for the hypothesis that the direction of DA modulation depends on the glutamate receptor subtype, as well as the DA receptor subtype activated. One possible consequence of these observations is that endogenous DA may be an important contributing factor in the mechanisms of cell death in Huntington's disease.
Spreading depression determines acute cellular damage in the hippocampal slice during oxygen/glucose deprivation
Authors: Obeidat Akef S. , Andrew R. David 
Published: March 2003

AbstractDuring ischaemia neurons depolarize and release the neurotransmitter l‐glutamate, which accumulates extracellularly and binds to postsynaptic receptors. This initiates a sequence of events thought to culminate in immediate and delayed neuronal death. However, there is growing evidence that during ischaemia the development of spreading depression (SD) can be an important determinant of the degree and extent of ischaemic damage. In contrast, SD without metabolic compromise (as occurs in migraine aura) causes no discernible damage to brain tissue. SD is a profound depolarization of neurons and glia that propagates like a wave across brain tissue. Brain cell swelling, an early event of both the excitotoxic process and of SD, can be assessed by imaging associated intrinsic optical signals (IOSs). We demonstrate here that IOS imaging clearly demarcates the ignition site and migration of SD across the submerged hippocampal slice of the rat. If SD is induced by elevating [K+]o, the tissue fully recovers, but in slices that are metabolically compromised at 37.5 °C by oxygen/glucose deprivation (OGD) or by ouabain exposure, cellular damage develops only where SD has propagated. Specifically, the evoked CA1 field potential is permanently lost, the cell bodies of involved neurons swell and their dendritic regions increase in opacity. In contrast to OGD, bath application of l‐glutamate (6–10 mm) at 37.5 °C evokes a non‐propagating LT increase in CA1 that reverses without obvious cellular damage. Moreover, application of 2–20 mm glutamate or various glutamate agonists fail to evoke SD in the submerged hippocampal slice. We propose that SD and OGD together (but not alone) constitute a ‘one‐two punch’, causing acute neuronal death in the slice that is not replicated by elevated glutamate. These findings support the proposal that SD generation during stroke promotes and extends acute ischaemic damage.