bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calpain Inhibitors Protect Against Depolarization‐induced Neurofilament Protein Loss of Septo‐hippocampal Neurons in Culture
Authors: Kampfl A. , Zhao X. , Whitson J. S. , Posmantur R. , Dixon C. E. , Yang K. , Clifton G. L. , Hayes R. L. 
Published: April 2006

AbstractWe examined the effect of a 6 min depolarization with 60 mM KCl and 1.8, 2.8 or 5.8 mM extracellular CaCl2 on neurofilament proteins of high (NF‐H), medium (NF‐M) and low (NF‐L) molecular weight in primary septo‐hippocampal cultures. One day after depolarization, Western blot analyses revealed losses of all three neurofilament proteins. Increasing the extracellular calcium concentration from 1.8 to 5.8 mM CaCl2 in the presence of 60 mM KCl produced increased losses of all three neurofilament proteins to ˜80% of control values in the absence of cell death. Calcium‐dependent losses of the neurofilament proteins correlated with calcium‐dependent increases in calpain 1‐mediated breakdown products of alpha‐spectrin. Calpain inhibitors 1 and 2, applied immediately after depolarization and made available to cultures for 24 h, reduced losses of all three neurofilament proteins to ˜14% of control values. The protective effects of calpain inhibitors 1 and 2 were influenced by different levels of extracellular calcium. Qualitative immunohistochemical evaluations confirmed semiquantitative Western blot data on neurofilament loss and protection by calpain inhibitors 1 and 2. We propose that brief depolarization causes loss of neurofilament proteins, possibly due to calpain activation. Thus, calpain inhibitors could represent a viable strategy for preserving the cytoskeletal structure of injured neurons.
Planning and Spatial Working Memory: a Positron Emission Tomography Study in Humans
Authors: Owen Adrian M. , Doyon Julien , Petrides Michael , Evans Alan C. 
Published: April 2006

AbstractPrevious work with both neurosurgical and neurodegenerative patient groups has suggested that high level planning is mediated by neural circuitry which includes both the prefrontal cortex and the striatum. In this study, the functional anatomy of cognitive planning was investigated further, using positron emission tomography (PET). Regional cerebral blood flow (rCBF) was measured in 12 normal volunteers while performing easy and difficult versions of (i) a modified Tower of London planning task; (ii) a mnemonic variant of this task that required short‐term retention and reproduction of problem solutions; and (iii) a control condition that involved identical visual stimuli and motor responses. Significant increases in rCBF were observed in the left hemisphere, in both the mid‐dorsolateral frontal cortex and in the head of the caudate nucleus, when the difficult planning task was compared with the control condition. Moreover, subtraction of a simple planning condition from the more difficult one revealed focal increases in rCBF in the caudate nucleus and the thalamus only. During both mnemonic variants of the planning task, changes were also observed in the mid‐dorsolateral frontal cortex and in more ventral frontopolar regions, bilaterally. When compared directly, the planning and memory conditions differed in terms of these ventral activation foci, but not in the pattern of activation observed in the mid‐dorsolateral frontal cortex. These findings further implicate frontostriatal circuitry in high‐level planning and provide evidence for functionally distinct contributions from ventral and dorsolateral frontal regions to spatial working memory.
Organization of the Visual Reticular Thalamic Nucleus of the Rat
Authors: Coleman Kristina A , Mitrofanis John 
Published: April 2006

AbstractThe visual sector of the reticular thalamic nucleus has come under some intense scrutiny over recent years, principally because of the key role that the nucleus plays in the processing of visual information. Despite this scrutiny, we know very little of how the connections between the reticular nucleus and the different areas of visual cortex and the different visual dorsal thalamic nuclei are organized. This study examines the patterns of reticular connections with the visual cortex and the dorsal thalamus in the rat, a species where the visual pathways have been well documented. Biotinylated dextran, an anterograde and retrograde tracer, was injected into different visual cortical areas [17; rostral 18a: presumed area AL (anterolateral); caudal 18a: presumed area LM (lateromedial); rostral 18b: presumed area AM (anteromedial); caudal 18b: presumed area PM (posteromedial)] and into the different visual dorsal thalamic nuclei (posterior thalamic, lateral posterior, lateral geniculate nuclei), and the patterns of anterograde and retrograde labelling in the reticular nucleus were examined. From the cortical injections, we find that the visual sector of the reticular nucleus is divided into subsectors that each receive an input from a distinct visual cortical area, with little or no overlap. Further, the resulting pattern of cortical terminations in the reticular nucleus reflects largely the patterns of termination in the dorsal thalamus. That is, each cortical area projects to a largely distinct subsector of the reticular nucleus, as it does to a largely distinct dorsal thalamic nucleus. As with each of the visual cortical areas, each of the visual dorsal thalamic (lateral geniculate, lateral posterior, posterior thalamic) nuclei relate to a separate territory of the reticular nucleus, with little or no overlap. Each of these dorsal thalamic territories within the reticular nucleus receives inputs from one or more of the visual cortical areas. For instance, the region of the reticular nucleus that is labelled after an injection into the lateral geniculate nucleus encompasses the reticular regions which receive afferents from cortical areas 17, rostral 18b and caudal 18b. These results suggest that individual cortical areas may influence the activity of different dorsal thalamic nuclei through their reticular connections.
Full‐length Cloning, Expression and Cellular Localization of Rat Plasmolipin mRNA, a Proteolipid of PNS and CNS
Authors: Gillen C. , Gleichmann M. , Greiner‐Petter R. , Zoidl G. , Kupfer S. , Bosse F. , Auer J. , Müller H. W. 
Published: April 2006

AbstractWe have isolated a 1.476 bp cDNA (NTII11) representing a transcript that is differentially expressed during sciatic nerve development and regeneration in the rat. Nucleotide sequence comparison indicates partial identity with a recently isolated plasmolipin cDNA. However, our clone extends the published sequence by 234 bp at the 5’end and predicts a protein that contains an additional 25 amino acids at the N‐terminus. The open reading frame of the NTII11 transcript encodes a 19.4 kDa protein with four putative transmembrane domains. Northern blot analyses revealed a tissue‐specific expression of the plasmolipin transcript that is restricted to sciatic nerve, brain and kidney. The neural expression was confirmed by in situ hybridization, and cellular localization of plasmolipin mRNA was demonstrated in Schwann cells of the sciatic nerve and in glial cells of myelinated brain structures. The steady‐state levels of plasmolipin mRNA were markedly altered (i) during development of the sciatic nerve and brain, (ii) after sciatic nerve injury, and (iii) in cultured Schwann cells maintained under different conditions of cell growth and arrest. Our data indicate a function of plasmolipin during myelination in the central as well as in the peripheral nervous system.
Expression of Glycine Receptor α Subunits and Gephyrin in Cultured Spinal Neurons
Authors: Béchade C. , Colin I. , Kirsch J. , Betz H. , Triller A. 
Published: April 2006

AbstractThe inhibitory glycine receptor is a pentameric membrane protein composed of α and β subunits. In the postsynaptic membrane, the glycine receptor and the copurifying peripheral membrane protein gephyrin are clustered underneath glycine‐releasing nerve terminals. Here, we describe the expression of gephyrin and the neonatal and adult glycine receptor α subunit isoforms α1 and α2 during in vitro differentiation of rat spinal neurons. Analysis by immunoassays and the reverse transcriptase—polymerase chain reaction showed that gephyrin and α subunit mRNA and protein levels exhibited a marked increase from 1 to 5 days in vitro, i.e. prior to the formation of functional synaptic contacts. Using confocal and standard immunofluorescence, we determined the number of immunoreactive cells and the cellular localization of the α subunits and gephyrin. At 3 days in vitro, glycine receptor immunoreactivity revealed by the monoclonal antibody mAb4a was found in >10% of cells and was mainly localized intracellularly; in contrast, gephyrin was detected in <50% of cells. At 7 days in vitro, gephyrin was essentially localized at the neuronal surface. At this stage, the number of glycine receptor‐positive cells approached that of gephyrin‐containing neurons (50%), and glycine receptor antigen was found both intracellularly and at the periphery of the cells. The antibody mAb2b, which binds exclusively to the α1 subunit, revealed aggregates at the surface of a few neurons. At 10 days in vitro, glycine receptor and gephyrin staining was localized in clusters at the periphery of the soma and the neurites. This quantitative analysis corroborates temporal differences in the cellular distribution of gephyrin and glycine receptor α subunits, the former being accumulated first at the neuronal surface.
Age‐related Changes in Excitability and Recurrent Inhibition in the Rat CA1 Hippocampal Region
Authors: Papatheodoropoulos Costas , Kostopoulos George 
Published: April 2006

AbstractIn hippocampal slices from male Wistar rats aged 1–34 months, we recorded the synaptic field potential responses of the CA1 neurons to stimulation of Schaffer collaterals. Eight electrophysiological indexes were extracted from input/output curves and compared in 11 age groups from 1 to 30 months. Neuronal excitability presented a U‐shaped curve of development with a minimum at ˜7–8 months of age. There was a significant continuous increase in neuronal excitability, i.e. a decrease in excitatory postsynaptic potential (EPSP) producing both the threshold and half‐maximal population spike from middle age (8–10 months) to senescence (30 months). Synaptic efficiency also increased in old rats to reach a maximum during senescence, i.e. both the current for threshold EPSP and that for half‐maximal EPSP reached a minimum in senescence, although the earlier developmental patterns of these two indexes were non‐linear. The duration of the field EPSP elicited with maximal stimulation presented an abrupt decay after the first month. Aged animals presented a relatively small maximal population spike. Recurrent inhibition was most prominent on neuronal excitability rather than synaptic strength. Measured as the percentage change in the half‐maximal EPSP and half‐maximal population spike, recurrent inhibition was found to decrease during the first 7–10 months of life and remained small in later development.
Interleukin 6 in Intact and Injured Mouse Peripheral Nerves
Authors: Reichert Fanny , Levitzky Rubina , Rotshenker Shlomo 
Published: April 2006

AbstractThe multifunctional cytokine interleukin 6 (IL‐6) has direct growth, survival and differentiation effects on peripheral and central neurons. Furthermore, it can modulate the production by non‐neuronal cells of other cytokines and growth factors, and thereby affect nerve cells indirectly. We have studied IL‐6 expression and production in intact and injured peripheral nerves of C57/BL/6NHSD mice, which display the normal rapid progression of Wallerian degeneration. The IL‐6 mRNA was detected in nerves degenerating in vitro or in vivo, but not in intact nerves. In vitro‐ and in vivo‐degenerating nerve segments and neuroma nerve segments synthesized and secreted IL‐6. The onset of IL‐6 production was rapid and prolonged. It was detected as early as 2 h after injury and persisted for the entire period of 21 days tested after the injury. Of the non‐neuronal cells that reside in intact and injured nerves, macrophages and fibroblasts were the major contributors to IL‐6 production. We also studied IL‐6 production in intact and injured nerves of mutant C57BL/6‐WLD/OLA/NHSD mice, which display very slow progression of Wallerian degeneration. Injured nerves of C57BL/6‐WLD/OLA/NHSD mice produced significantly lower amounts of IL‐6 than did rapidly degenerating nerves of C57/BL/6NHSD mice.
Differential Expression of Ubiquitous and Neuronal Kinesin Heavy Chains During Differentiation of Human Neuroblastoma and PC12 Cells
Authors: Vignali G. , Niclas J. , Sprocati M. T. , Vale R. D. , Sirtori C. , Navone F. 
Published: April 2006

AbstractKinesin is a microtubule‐based motor protein involved in intracellular organelle transport. Neurons are characterized by the presence of at least two isoforms of conventional kinesin: ubiquitous kinesin, expressed in all cells and tissues, and neuronal kinesin, whose pattern of expression is confined to neuronal cells. In order to investigate whether the two kinesin motors, which are encoded by different genes, may play distinct biological roles in neurons, we studied their expression during neuronal differentiation. Human neuroblastoma SH‐SY5Y and IMR32 cells and rat phaeochromocytoma PC12 cells were used as an in vitro system for neuronal differentiation and were induced to differentiate in the presence of retinoic acid, a combination of dibutyryl cAMP and 5‐bromodeoxyuridine, and nerve growth factor respectively. The expression level of each kinesin isoform was evaluated by quantitative immunoblot before and after pharmacological treatment. We found that in all cell types the expression level of neuronal kinesin, but not of ubiquitous kinesin, is stimulated during differentiation. In particular, SH‐SY5Y cells show a 4.5‐fold, IMR32 cells a 3‐fold and PC12 cells a 7‐fold increase in the level of expression of neuronal kinesin. By Northern blot analysis we found that the selective increase in the expression of neuronal kinesin is paralleled by an increase in its mRNA, indicating that there is a transcriptional control of the expression of this kinesin isoform during differentiation of neuroblastoma and PC12 cells. Our results suggest that these cells represent an adequate model to study the function of conventional kinesin and its isoforms.
Regulation of Rat Schwann Cell Po Expression and DNA Synthesis by Insulin‐like Growth Factors In Vitro
Authors: Stewart Helen J. S. , Bradke Frank , Tabernero Arantxa , Morrell David , Jessen Kristjan R. , Mirsky Rhona 
Published: April 2006

AbstractMyelination by Schwann cells is likely to be regulated in Vitro by positive and negative epigenetic factors. In Vitro, the positive regulation of myelin differentiation, in particular expression of the major myelin protein Po, can be mimicked by cAMP elevating agents, while serum, transforming growth factor (TGF)βs, and fibroblast growth factor (FGF)2 have been shown to exert a negative effect on this differentiation. Growth factors which promote Po induction have not, however, been identified previously. Using a forskolin concentration (0.4 μM) which alone produces little Po mRNA or protein induction, we show that insulin‐like growth factor (IGF)‐I, IGF‐II and high concentrations of insulin promote high levels of Po induction, although in the absence of forskolin they have no effect. Another event related to Schwann cell differentiation, induction of galactocerebroside expression in response to cAMP analogues, is also potentiated by IGFs. In a different context, IGFs regulate Schwann cell DMA synthesis. We find that in defined medium forskolin plus FGF2, TGFβ or platelet‐derived growth factor (PDGF) BB causes minimal DNA synthesis in the absence of IGFs and that IGFs act as potent mitogens under these conditions. IGFs also potentiate DNA synthesis induced by β isoforms of neu‐differentiation factors (NDFs), although in this case considerable DNA synthesis occurs even in the absence of IGF. These results show that IGFs can act as powerful stimulators of both proliferation and differentiation in Schwann cells, and that the total growth factor input determines which of these pathways IGFs will promote.
Effects of the Uncompetitive NMDA Receptor Antagonist Memantine on Hippocampal Long‐term Potentiation, Short‐term Exploratory Modulation and Spatial Memory in Awake, Freely Moving Rats
Authors: Barnes Carol A. , Danysz Wojciech , Parsons Chris G. 
Published: April 2006

AbstractChronic treatment of adult male F‐344 rats (9–12 months old) with therapeutically relevant doses of memantine (30 mg/kg/day in chow for <8 weeks) increased the maintenance of long‐term potentiation of field excitatory postsynaptic potentials from perforant path—granule cell hippocampal synapses recorded in the fascia dentata in vivo. In contrast, there was no effect of memantine on baseline synaptic responses or population spikes. Likewise, short‐term exploratory modulation of these hippocampal evoked responses was not different between memantine‐treated and control rats. Both groups of rats were able to learn the spatial version of the Morris water task equally well, but the memantine‐treated group showed a strong tendency to show more selective spatial search patterns in the training quadrant of the water pool during a final probe trial. As such, these studies provide the first electrophysiological evidence that memantine can increase the durability of synaptic plasticity and provide preclinical confirmation of the cognitive improvement seen with memantine in the treatment of demented patients.
Activation and Proliferation of Murine Microglia are Insensitive to Glucocorticoids in Wallerian Degeneration
Authors: Castaño A. , Lawson L. J. , Fearn S. , Perry V. H. 
Published: April 2006

AbstractActivation and proliferation of microglia are commonly described in the central nervous system after a wide range of insults, but the mechanisms that regulate their phenotype in vivo are still poorly understood. We have studied the effect that adrenalectomy and dexamethasone treatment have on the proliferation and activation of microglia during Wallerian degeneration of the optic nerve in BALB/c mice. We found that the onset and rate of microglia proliferation is independent of glucocorticoids. There was an increase in F4/80‐positive cells 3 days after optic nerve crush, with a peak at 7 days, both in the optic nerve and its target, the superior colliculus. The numbers of F4/80‐positive cells remained high up to 3 weeks after crush, the longest time point examined. We also found that up‐regulation of F4/80 and the complement receptor type 3 and expression of major histocompatibility complex class II antigens were not affected by adrenalectomy or dexamethasone treatment. These observations show that, unlike microglia in vitro or peripheral macrophages, microglia do not readily respond to glucocorticoids, which could indicate a lack of or reduced expression of glucocorticoid receptor in these cells.
Clusterin (SGP‐2) Induction in Rat Astroglial Cells Exposed to Prion Protein Fragment 106–126
Authors: Chiesa Roberto , Angeretti Nadia , Lucca Elisa , Salmona Mario , Tagliavini Fabrizio , Bugiani Orso , Forloni Gianluigi 
Published: April 2006

AbstractPrion‐related encephalopathies are characterized by the accumulation of an abnormal prion protein isoform (PrPSc) associated with neuronal degeneration and astrogliosis. The synthetic peptide homologous to PrP fragment 106–126 (PrP 106–126) induced in vitro neuronal apoptosis and glial proliferation. We used Northern blot analysis and the RNA polymerase chain reaction to assess the expression of several genes associated with programmed cell death and proliferation. Blots of total RNA extracted from neuronal and astroglial cells exposed to PrP 106–126 for between 1 h and 7 days were hybridized with probes recognizing c‐fos, c‐jun, c‐myc, p53, hsp‐70 and bcl‐2 mRNA. Except for a slight decrease in bcl‐2 mRNA in neuronal cells, no change in other transcripts was evident. Since clusterin (apolipoprotein J) mRNA levels are increased in prion‐related encephalopathies and clusterin immunoreactivity has been located in association with PrPSc in Gerstmann‐Sträussler‐Scheinker brain, the expression of clusterin was determined in neuronal and astroglial cells chronically exposed to PrP 106–126. Although the induction of clusterin has been involved in the apoptotic mechanism in other experimental conditions, its expression was unchanged in PrP 106–126‐treated neurons, while a three‐fold induction of clusterin mRNA was observed in astrocytes exposed to PrP 106–126. To investigate whether the clusterin up‐regulation was simply associated with the astroglial proliferative stimulus of PrP 106–126 or was specifically induced by the peptide, we measured clusterin expression in astrocytes cultured in fetal calf serum‐free medium and exposed to PrP 106–126 or fetal calf serum restoration. In this condition the PrP peptide, like fetal calf serum, increased the glial proliferation rate, but only PrP 106–126 doubled clusterin mRNA. The selectivity of this effect indicates that PrPSc is directly involved in the clusterin up‐regulation seen in prion‐related encephalopathies and is associated with astroglial cells.
Muscarinic Activation of a Novel Voltage‐sensitive Inward Current in Rabbit Prevertebral Sympathetic Neurons
Authors: Delmas P. , Niel J. P. , Gola M. 
Published: April 2006

AbstractThe muscarinic activation of rabbit prevertebral sympathetic neurons was studied in non‐dissociated coeliac and superior mesenteric ganglia using whole‐cell patch‐clamp techniques. In the presence of nicotinic blockers, carbachol, muscarine and oxotremorine‐M (1–50 μM) induced tonic firing by activating a persistent inward current. These effects were abolished by atropine. They persisted when the M‐current was blocked with Ba2+ (1 mM) and intracellular Cs+. The muscarinic inward current was found to be time‐ and voltage‐dependent. It peaked at ‐60 mV, decreased at large hyperpolarizations and was tonically activated between —110 and —20 mV, which gave steady‐state I—V curves an N‐shape between —96 and —54 mV. The negative slope accounted for the large hyperpolarizing responses generated by current pulses in carbachol‐treated cells. The muscarinic current was abolished when Na+ was replaced by choline, Tris+, sucrose, N‐methyl‐D‐glucamine and Cs+ but not Li+. It was resistant to tetrodotoxin (3 μM), amiloride (3 μM), benzamil (10 μM) and tetraethylammonium (5–20 mM). No involvement of K+ and Cl‐ could be detected. We therefore styled it lNa, M, in reference to its ionic selectivity and its coupling to muscarinic receptors. Low Ca2+‐Mg2+ salines enhanced the Na, M‐current. The current was blocked by Cd2+, Co2+, La3+ (1 mM) and Ba2+ (5 mM) but insensitive to methoxyverapamil hydrochloride, nicardipine, nifedipine and ω‐conotoxin MVII A (2–20 μM). These effects were ascribed to the binding of di‐ and trivalent ions to the Na, M‐channels. Spike bursts transiently blocked lNa, M. With high intracellular ethylene glycol bis(b‐aminoethyl ether)‐N, N'‐tetraacetic acid or 1, 2‐bis(2‐aminophenoxy)ethane‐N, N, N', N'‐tetraacetic acid (20–50 mM), this effect was reduced, whereas lNa, M persisted in long‐term recordings and its amplitude increased twofold, indicating that intracellular calcium negatively regulated the Na, M‐channels. We conclude that we have described a novel muscarinic receptor‐coupled channel which appears to play a major part in regulating the firing behaviour of sympathetic neurons.