bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noradrenaline Increases K‐conductance and Reduces Glutamatergic Transmission in the Mouse Entorhinal Cortex by Activation of α2‐Adrenoreceptors
Authors: Pralong Etienne , Magistretti Pierre J. 
Published: April 2006

AbstractThe entorhinal cortex is a gateway to the hippocampus; it receives inputs from several cortical associative areas as well as subcortical areas. Since there is evidence showing that noradrenaline reduces the epileptic activity generated in the entorhinal cortex, we have examined the action of noradrenaline in the superficial layer of the entorhinal cortex, which is the main source of afferents to the hippocampus. In a previous study we showed that noradrenaline hyperpolarized layer II entorhinal cortex neurons and reduced global synaptic transmission via α2‐adrenoreceptors. Here we present a detailed analysis of the effect of noradrenaline on membrane resistance and on the pharmacologically isolated postsynaptic potentials in layer II entorhinal cortex neurons of mice. Noradrenaline (50 μM) hyperpolarized most layer II entorhinal cortex neurons. This hyperpolarization corresponded to an outward current with a reversal potential following the Nernst equilibrium potential for potassium. The hyperpolarizing effect of noradrenaline was blocked by 10 μM yohimbine. These observations suggest that noradrenaline activates a potassium conductance via an α2‐adrenoreceptor. Noradrenaline (10–50 μM) reversibly reduced the amplitude of the pharmacologically isolated excitatory potentials mediated by both NMDA and α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐propionic acid (AMPA) receptors, the former being more strongly affected. Again this effect was blocked by 10 μM yohimbine. In contrast, GABAA‐mediated synaptic transmission was virtually unaffected by noradrenaline. Thus, noradrenaline appears to strongly inhibit the glutamate‐mediated synaptic transmission in the entorhinal cortex without affecting inhibitory post‐synaptic potentials. These observations suggest that α2‐adrenergic receptor agonists may exert a beneficial effect in the control of hyperexcitability in temporal lobe epilepsy.
High Specificity of Neurotrophins in the Embryonic Chicken Trigeminal System
Authors: Pinon Luzia G. P. , Robinson Michelle , Davies Alun M. 
Published: April 2006

AbstractStudies of cell lines and some cultured neurons have demonstrated potential cross‐talk between neurotrophins and their receptors; high concentrations of neurotrophins can exhibit either agonist or antagonistic actions on heterologous neurotrophin receptors. We have studied neurotrophin discrimination among the sensory neurons of the embryonic chicken trigeminal system. We show that nerve growth factor (NGF) at a concentration that is six orders of magnitude greater than that required to promote the survival of NGF‐dependent dorsomedial trigeminal ganglion (DMTG) neurons has no effect on the survival of brain‐derived neurotrophic factor (BDNF)‐dependent trigeminal mesencephalic nucleus (TMN) neurons and does not affect the dose‐response relationship of these neurons to BDNF. A similar high level of neurotrophin‐3 neither promotes the survival of BDNF‐dependent ventrolateral trigeminal ganglion neurons nor affects the dose response of these neurons to BDNF. High levels of BDNF have a negligible effect on the survival of mid‐embryonic DMTG neurons. These results show that some neurons are able to discriminate completely between neurotrophins at very high concentrations, indicating that neurotrophin responses can be far more highly specific than previously appreciated.
Membrane Potential Oscillations of Neonatal Rat Spinal Motoneurons Evoked by Electrical Stimulation of Dorsal Root Fibres
Authors: Baranauskas Gytis , Nistri Andrea 
Published: April 2006

AbstractIntracellular recording from lumbar motoneurons of the neonatal rat isolated spinal cord bathed in standard saline solution was used to study membrane potential oscillations which accompanied the decay phase of excitatory postsynaptic potentials (EPSP) induced by single electrical pulses to an adjacent dorsal root. About 60% of motoneurons displayed rhythmic oscillations of 10 ± 2 mV maximal amplitude and 7 ± 0.5 Hz frequency. Ability to generate oscillations could not be correlated to the cell membrane properties or to the age of the preparation (5–13 days). The oscillation frequency was independent of membrane potential (‐100 to ‐45 mV) or of the intensity of dorsal root stimuli. The oscillation amplitude was linearly related to the cell potential within the same voltage level. Fast Fourier transform analysis showed that the power spectrum of oscillations peaked at ˜8 Hz. Electrically evoked activities and spontaneous events displayed similar cut‐off frequencies. When the cell membrane potential was steadily depolarized, a hyperpolarizing pulse applied during the decay phase of the EPSP promptly revealed the presence of oscillatory behaviour. Pharmacological block of neurokinin‐1 or N‐methyl‐D‐aspartate receptors depressed the decay phase of the EPSP and the associated oscillatory responses. It is suggested that rhythmic oscillations were probably due to summated synaptic potentials generated at the premotoneuron level and are perhaps of functional relevance to motoneuron behaviour.
Inhibitors of Type IV Phosphodiesterases Reduce the Toxicity of MPTP in Substantia Nigra Neurons In Vivo
Authors: Hulley Philippa , Hartikka Jukka , Abdel'Al Samir , Engels Peter , Buerki Hans‐Rudolf , Wiederhold Karl‐Heinz , Müller Thomas , Kelly Peter , Lowe David , Lübbert Hermann 
Published: April 2006

AbstractThe neuropathology of Parkinson's disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra. We have recently shown that the activation of protein kinase A improves the survival of dopaminergic neurons in culture and, furthermore, protects them from the dopaminergic neurotoxin, 1‐methyl‐4‐phenylpyridinium ion (MPP+) in vitro. We have now analysed the potential of phosphodiesterase inhibitors to increase cAMP levels in dopaminergic neurons, to improve their survival in culture and to protect them from the toxicity of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) in vivo. Increasing intracellular cAMP with phosphodiesterase type IV‐specific inhibitors enhanced the survival of dopaminergic neurons in culture. Inhibitors of other phosphodiesterase types were not active. In vivo, phosphodiesterase type IV inhibitors reduced the MPTP‐induced dopamine depletion in the striatum of C57BL/6 mice. Furthermore, the loss of tyrosine hydroxylase‐immunopositive neurons in the substantia nigra of these animals was diminished. After Nissl staining, a similar reduction of the MPTP‐induced loss of neurons was observed in the substantia nigra. The protective effect of protein kinase A activation did not appear to be due to the blocking of MPP+ uptake into dopaminergic neurons. This was not decreased after treatment with forskolin or 8‐(4‐chlorophenylthio)‐cAMP. Thus, protein kinase A regulates the survival and differentiation of dopaminergic substantia nigra neurons in vivo, implicating a therapeutic potential for substances which regulate cAMP turnover in these neurons.
IL‐6 Expression in Neurons of Transgenic Mice Causes Reactive Astrocytosis and Increase in Ramified Microglial Cells but no Neuronal Damage
Authors: Fattori Elena , Lazzaro Domenico , Musiani Piero , Modesti Andrea , Alonzi Tonino , Ciliberto Gennaro 
Published: April 2006

AbstractGrowing evidence suggests that aberrant production of inflammatory cytokines within the central nervous system (CNS) contributes to the development of pathological conditions. To test the cause—effect relationship between the overproduction of interleukin‐6 (IL‐6) in the CNS and the onset of neuropathological changes, we have generated transgenic mice in which human IL‐6 expression has been targeted to the neurons by using the rat neuron‐specific enolase promoter. These mice develop reactive astrocytosis and an increase in ramified microglial cells but do not show histological or behavioural signs of neuron damage at the light microscope level. We thus conclude that a constant release of human IL‐6 by neuronal subpopulations in mice is sufficient to activate cells potentially capable of modulating the local immune response, but at the same time is compatible with normal neuron functions.
Dopamine Autoreceptor Sensitivity is Unchanged in Rat Nucleus Accumbens After Chronic Haloperidol Treatment: An In Vivo and In Vitro Voltammetric Study
Authors: Chesi Alexander J. R. , Feasey‐Truger Karin J. , Alzheimer Christian , Bruggencate Gerrit ten 
Published: April 2006

AbstractFast cyclic voltammetry was used to assess the effects of chronic oral haloperidol treatment (0.7 mg/kg/day for 21 days) on the sensitivity of dopamine autoreceptors in the rat nucleus accumbens both in vivo and in vitro. Evoked dopamine overflow was significantly reduced after chronic haloperidol treatment, but the sensitivity of dopamine overflow to sulpiride, an antagonist at release‐inhibiting dopamine autoreceptors, and quinpirole, an agonist at these receptors, was unchanged. The estimated EC50 values for quinpirole and sulpiride (52 and 60 nM respectively) obtained in vitro and the receptor distribution profiles published in the literature suggest that the autoreceptors involved in this modulation are mainly of the D3 subtype. The finding that the reduced dopamine overflow in the nucleus accumbens observed after chronic treatment with a classical neuroleptic is not due to dopamine autoreceptor supersensitivity may therefore be the first functional evidence for unchanged autoreceptor activity in the nucleus accumbens, supporting biochemical findings of a lack of D3 autoreceptor up‐regulation after chronic haloperidol treatment. It lends further support to the assumption that the long‐term changes occurring during chronic neuroleptic treatment may not lie at the level of presynaptic dopamine receptor regulation.
Prominent Expression of bFGF in Dorsal Root Ganglia after Axotomy
Authors: Ji R.‐R. , Zhang Q. , Zhang X. , Piehl F. , Reilly T. , Pettersson R. F. , Hökfelt T. 
Published: April 2006

AbstractUsing quantitative in situ hybridization and immunohistochemistry the expression of acidic and basic fibroblast growth factors (aFGF, bFGF) in dorsal root ganglia (DRGs) was examined. Around 5% of the small neurons expressed bFGF mRNA in normal DRGs. Nerve injury induced a very dramatic and rapid up‐regulation in bFGF mRNA levels, and around 80% of all DRG neurons expressed bFGF mRNA 3 days after axotomy. A distinct increase in bFGF‐like immunoreactivity (LI) was also detected as early as 15 h after axotomy. The elevation of bFGF mRNA and protein levels declined after 1 week. bFGF mRNA was also up‐regulated in non‐neuronal cells following axotomy. Normally bFGF‐LI was mainly localized in the nuclei of DRG neurons and in some non‐neuronal cells. After nerve section, bFGF‐LI was in addition found in the cytoplasm, and many more bFGF‐positive non‐neuronal cells were observed. By means of confocal microscopy analysis of axotomized DRGs, some bFGF‐LI could be detected in vesicle‐like structures in the cytoplasm as well as in the nucleoli, in addition to the nuclear location. Application of leukaemia inhibitory factor to the transected sciatic nerve significantly increased the number of bFGF‐positive neurons, whereas the bFGF‐LI in non‐neuronal cells was strongly suppressed. About 70% of the normal DRG neurons expressed aFGF mRNA and aFGF‐LI. Axotomy produced a moderate increase in aFGF mRNA levels, but no detectable effect on protein levels. Taken together, the results show that bFGF may be involved in the neuronal response to injury and suggest a role in neuronal survival and regeneration in axotomized DRG neurons.
Quantification of Normal Cell Death in the Rat Retina: Implications for Clone Composition in Cell Lineage Analysis
Authors: Voyvodic James T. , Burne Julia F. , Raff Martin C. 
Published: April 2006

AbstractNaturally occurring cell death complicates the analysis of cell lineage studies by making the surviving members of a clone appear more closely related than they actually are. Here we ask how much normal cell death occurs during rat retinal development, and whether that amount of death is sufficient to confuse the analysis of cell lineage relationships. We measure total cell death in the retina by combining relative counts of dead cells with absolute measurements of total cell loss. For most cell types, but not rods, we find that half of the cells generated die during normal retinal development. We use a computer model to quantify the effects of different amounts of cell death in a simulated lineage study. The simulation indicates that 50% cell death means that clonal variability analysed after the cell death period is not necessarily a good indicator of how much variability actually occurs in the underlying lineage.
Inhibition of PC12 Cell Attachment and Neurite Outgrowth by Detergent Solubilized CNS Myelin Proteins
Authors: Rubin Beatrix P. , Spillmann Adrian A. , Bandtlow Christine E. , Hillenbrand Rainer , Keller Flavio , Schwab Martin E. 
Published: April 2006

AbstractAdhesion and neurite outgrowth of PC12 cells, as well as the spreading of 3T3 fibroblasts, were inhibited in a dose dependent manner by detergent solubilized mouse central nervous system myelin proteins as a tissue culture substrate. These inhibitory effects could be neutralized by the monoclonal antibody IN‐1 directed against the neurite growth inhibiting proteins NI‐35 and NI‐250. Separation of the detergent soluble proteins of bovine spinal cord by an anion exchange column showed that the peaks of inhibitory activity for the two cell lines overlapped, such that the PC12 cells were inhibited by a larger number of fractions comprising those inhibitory for 3T3 cells. Neurite outgrowth of PC12 cells was not influenced by the myelin associated glycoprotein, MAG.
Effects of Changes in Rat Brain Glucose on Serotonergic and Noradrenergic Neurons
Authors: Vahabzadeh Abdolvahab , Boutelle Martyn G. , Fillenz Marianne 
Published: April 2006

AbstractMicrodialysis was used in the freely moving rat to measure the effects of graded changes in brain glucose on the serotonergic and noradrenergic projections to the hippocampus. The concentration of glucose in the dialysate was monitored using an enzyme‐based assay. A systemic injection of insulin caused a steep decline in glucose level which was restored to the control level by oral administration of glucose solution. The changes in 5‐hydroxytryptamine (5‐HT) and noradrenaline were a mirror image of the glucose changes: they rose after insulin injection and returned to control during glucose administration. A delayed increase was shown by 5‐hydroxyindoleacetic acid (5‐HIAA) which did not return to baseline on glucose administration. The metabolite dihydroxyphenylacetic acid (DOPAC) decreased after insulin administration and increased above control during glucose administration. While the responses of 5‐HT, noradrenaline and 5‐HIAA to hypoglycaemia resemble those to mild stress, the changes in DOPAC are the reverse of those produced by stress.
Identification, Distribution and Physiological Activity of Three Novel Neuropeptides of Lymnaea: FLRlamide and pQFYRlamide Encoded by the FMRFamide Gene, and a Related Peptide
Authors: Santama Niovi , Wheeler Colin H. , Skingsley David R. , Yeoman Mark S. , Bright Kerris , Kaye Iain , Burke Julian F. , Benjamin Paul R. 
Published: April 2006

AbstractWe are interested in analysing the detailed modulation of defined neuronal systems by multiple neuropeptides encoded in the FMRFamide locus of the snail Lymnaea. Cloning of the FMRFamide gene has predicted the existence of two novel peptides previously unknown from biochemical analysis, the pentapeptides EFLRlamideand QFYRlamide. These peptides may form part of a new family of peptides sharing the sequence motif –FXRlamide. In this paper we adopt a novel approach to first identify and characterize –FXRlamide‐like peptides in extracts from the central nervous system of Lymnaea. By a combination of high‐performance liquid chromatography (HPLC) and continuous‐flow fast atom bombardment mass spectrometry, we identify three novel peptides: EFLRlamide, pQFYRlamide and pQFLRlamide. The first two are those predicted in exon II of the FMRFamide locus whereas the last is, interestingly, a product which cannot be derived from post‐translational modification of the predicted peptides but must be encoded by as yet unidentified nucleotide sequences. A specific antibody raised to EFLRlamide, and immuno reactive to all three peptides, revealed EFLRlamide‐like expression throughout the central nervous system in the same cells where exon II is transcribed and the peptide SEEPLY (a post‐translational product of exon II) was localized. Additional cells, however, were also identified. Immunoreactivity was mapped in a number of identified neurons in the central nervous system, including two heart cardio excitatory motoneurons, the Ehe cells (E heart excitors of the visceral ganglion) and penialmotoneurons in the right cerebral ganglion. The peripheral tissues (heart and penial complex) that the serespective classes of neurons innervate also exhibited EFLRlamide immunoreactivity. The central and peripheral localization of EFLRlamide‐like immunoreactivity suggested that EFLRlamide/pQFYRlamide may have an important physiological role in both these peripheral systems as well as in the central nervous system. This was confirmed by physiological experiments that showed that EFLRlamide and pQFYRlamide inhibited many centralneurons and in particular the Bgp neurons in the right parietal ganglion. EFLRlamide had complex biphasic effects on the frequency of heart‐beat: an initial inhibitory response was followed by a long‐lasting increase in the rate of beating. Taken together with earlier work, this study now completes the analysis and localization of the full set of post‐translational products of the FMRFamide precursor in Lymnaea and supplies further evidence towards the characterization of the physiological systems which such peptides may modulate in concert.
NMDA Receptor‐dependent Long‐term Potentiation in the Hippocampal Afferent Fibre System to the Prefrontal Cortex in the Rat
Authors: Jay Thérèse M. , Burette François , Laroche Serge 
Published: April 2006

AbstractThis study investigated the role of the N‐methyl‐d‐aspartate (NMDA) subtype of glutamate receptor in the induction of long‐term potentiation (LTP) in the hippocampal‐prefrontal cortex pathway in vivo. Field potentials evoked by electrical stimulation of the CA1/subicular region were recorded in the prelimbic area of the prefrontal cortex under continuous perfusion of artificial cerebrospinal fluid in anaesthetized rats. High‐frequency stimulation of the CA1/subicular region induced LTP of the evoked response in the prelimbic area of the prefrontal cortex. LTP was completely blocked when the selective NMDA receptor antagonist d‐(‐)2‐amino‐5‐ phosphonopentanoic acid (d‐AP5; 200 μM), was perfused during the tetanus. Perfusion of D‐AP5 did not affect normal transmission or pre‐established LTP. These results demonstrate that induction of LTP in the hippocampal‐prefrontal cortex pathway is an NMDA receptor‐dependent process.
The Effects of AMPA‐induced Lesions of the Septo‐hippocampal Cholinergic Projection on Aversive Conditioning to Explicit and Contextual Cues and Spatial Learning in the Water Maze
Authors: McAlonan Gráinne M. , Wilkinson Lawrence S. , Robbins Trevor W. , Everitt Barry J. 
Published: April 2006

AbstractThe environmental context of an animal both subsumes and is associated with the explicit cues that guide its behavioural responses. Recent work in this laboratory suggests that learning about the relationship between the cues which comprise a context depends on the hippocampus. In the present study the role of the cholinergic input to the hippocampus in contextual learning was assessed in rats using a conditioned stimulus/context conditioning paradigm and spatial learning in the Morris water maze. In the former, a place preference apparatus provided the context. The subject was confined in the black chamber and a ‘clicker’conditioned stimulus was presented five times in a 20 min period. A trace interval of 5 or 30 s, depending on the group, was interposed between the end of the clicker and a footshock. Theory predicts that animals in the 5 s condition will learn more about the clicker as a predictor of shock and become strongly conditioned, while those in the 30 s condition learn relatively more about the context. Conditioning to the clicker (conditioned stimulus) was measured in a separate lick suppression chamber—presentation of the clicker suppresses drinking, and contextual learning was determined by recording the time spent on the black side of the place preference apparatus when both the black and a familiar white chamber were accessible. Lesions of the medial septum/ diagonal band induced by RS‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) enhanced contextual learning in this paradigm but disrupted conditioned stimulus conditioning in the 30 s condition. Acquisition of the Morris water maze was largely unimpaired. The results are suggested to reflect a shift towards the use of hippocampal‐dependent contextual learning strategies in lesioned animals.
Changes in Protein Kinase C and its Presynaptic Substrate B‐SO/GAP‐43 after Intrauterine Exposure to Methylazoxy‐methanol, a Treatment Inducing Cortical and Hippocampal Damage and Cognitive Deficit in Rats
Authors: Di Luca M. , Caputi A. , Cinquanta M. , Cimino M. , Marini P. , Princivalle A. , De Graan P. N. E. , Gispen W. H. , Cattabeni F. 
Published: April 2006

AbstractThe involvement of protein kinase C (PKC)‐dependent processes in adaptive and plastic changes underlying neuronal plasticity was tested in an in vivo animal model characterized by targeted cellular ablation of cortical and hippocampal neurons, cognitive impairment and lack of induction of long‐term potentiation. [3H]Phorbol ester binding performed on brain slices revealed a 67.4 and 35.0% increase in membrane‐bound protein kinase C in the cortex and hippocampus respectively of rats treated with methylazoxy‐methanol acetate compared with saline‐treated control rats, and there was no modification in the expression of mRNAs of different protein kinase C isozymes. In situ phosphorylation experiments performed with 32Pi‐labelled synaptosomes from the affected areas demonstrated that the phosphorylation of the nervous tissue‐specific presynaptic membrane‐associated protein kinase C substrate B‐50lGAP‐43 was increased by 51.4 and 44.8% in cortex and hippocampus respectively. Western blot analysis of protein kinase C in synaptosomal cytosol and membrane fractions prepared from cortex and hippocampus showed an increased proportion of protein kinase C in the membrane compartment in treated animals, but no change in the total synaptosomal protein kinase C activity. Our data are consistent with increased activity of presynaptic protein kinase C and predict a sustained increase in glutamate release in methylazoxy‐methanol‐treated rats.