bluuebunny/crossref_metadata_2025_split huggingface dataset:
Müller Glia Stabilizes Cell Columns During Retinal Development: Lateral Cell Migration but not Neuropil Growth is Inhibited in Mixed Chick‐Quail Retinospheroids
Authors: Willbold Elmar , Reinicke Michael , Lance‐Jones Cynthia , Lagenaur Carl , Lemmon Vance , Layer Paul G. 
Published: April 2006

AbstractRadial columnar organization of cell clones is a characteristic feature of vertebrate retinae that is structurally not understood. Here we provide in vitro evidence that Müller glia processes stabilize cells within columns. Dissociated embryonic chick retinal plus pigmented cells regenerate in vitro into fully laminated stratospheroids. After reaggregating chick and quail cells, quail‐derived spheroid areas are detected as isolated sectors, as shown by a quail‐specific antibody. Each sector contains one or multiple cell columns. The radial borders separating chick and quail sectors are fully congruent with the extension of 3A7‐labelled Müller glia processes. While cell somata do not show any lateral interspecies mixing, quail‐derived neuropil extends within the inner plexiform areas far into chick sectors. After selective damage of Müller cells by the gliotoxin dl‐α‐aminoadipic acid, the columnar organization is destabilized, as evidenced by a decrease in vimentin expression and by the migration of individual neurons out of their cell column. These data demonstrate that Müller cells actively stabilize cells within their columns, while neuritic growth is not hindered.
HIV‐1 Envelope Proteins gp120 and gp160 Potentiate NMDA‐induced [Ca2+]i Increase, Alter [Ca2+]i Homeostasis and Induce Neurotoxicity in Human Embryonic Neurons
Authors: Lannuzel Annie , Lledo Pierre‐Marie , Lamghitnia Hassan Ould , Vincent Jean‐Didier , Tardieu Marc 
Published: April 2006

AbstractThe envelope glycoprotein gp120 of the human immunodeficiency virus HIV‐1 has been proposed to cause neuron death in developing murine hippocampal cultures and rat retinal ganglion cells. In the present study, cultured human embryonic cerebral and spinal neurons from 8‐ to 10‐week‐old embryos were used to study the neurotoxic effect of gp120 and gp160. Electrophysiological properties as well as N‐methyl‐d‐aspartate (NMDA)‐induced currents were recorded from neurons maintained in culture for 10–30 days. Neither voltage‐activated sodium or calcium currents nor NMDA‐induced currents were affected by exposure of neurons to 250 pM gp120 or gp160. In contrast, when neurons were subjected to photometric measurements using the calcium dye indo‐1 to monitor the intracellular free Ca2+ concentration ([Ca2+]i), gp120 and gp160 (20–250 pM) potentiated the large rises in [Ca2+]i induced by 50 μM NMDA. The potentiation of NMDA‐induced Ca2+ responses required the presence of Ca2+ in the medium, and was abolished by the NMDA antagonist d‐2‐amino‐5‐phosphonovalerate (AP5) and the voltage‐gated Ca2+ channel inhibitor nifedipine. Moreover, exposure of a subpopulation of spinal neurons (25% of the cells tested) to 20–250 pM gp120 or gp160 resulted in an increase in [Ca2+]i that followed three patterns: fluctuations not affected by AP5, a single peak, and the progressive and irreversible rise of [Ca2+]i. The neurotoxicity of picomolar doses of gp120 and gp160 cultures was estimated by immuno‐fluorescence and colorimetric assay. Treatment of cultures with AP5 or nifedipine reduced gp120‐induced toxicity by 70 and 100% respectively.
Distribution of GLP‐1 Binding Sites in the Rat Brain: Evidence that Exendin‐4 is a Ligand of Brain GLP‐1 Binding Sites
Authors: Göke Rüdiger , Larsen Philip J. , Mikkelsen Jens D. , Sheikh Søren P. 
Published: April 2006

AbstractThe distribution and biochemical properties of glucagon‐like peptide (GLP)‐1(7–36)amide (GLP‐1) binding sites in the rat brain were investigated. By receptor autoradiography of tissue sections, the highest densities of [125I]GLP‐1 binding sites were identified in the lateral septum, the subfornical organ (SFO), the thalamus, the hypothalamus, the interpenduncular nucleus, the posterodorsal tegmental nucleus, the area postrema (AP), the inferior olive and the nucleus of the solitary tract (NTS). Binding studies with [125I][Tyr39]exendin‐4, a GLP‐1 receptor agonist, showed an identical distribution pattern of binding sites. Binding specificity and affinity was investigated using sections of the brainstem containing the NTS. Binding of [125I]GLP‐1 to the NTS was inhibited concentration‐dependently by unlabelled GLP‐1 and [Tyr39]exendin‐4 with K1 values of 3.5 and 9.4 nM respectively. Cross‐linking of hypothalamic membranes with [125I]GLP‐1 or [125I][Tyr39]exendin‐4 identified a single ligand‐binding protein complex with a molecular mass of 63 000 Da. The fact that no GLP‐1 binding sites were detected in the cortex but that they were detected in the phylogenetically oldest parts of the brain emphasizes that GLP‐1 may be involved in the regulation of vital functions. In conclusion, the biochemical data support the idea that the central GLP‐1 receptor resembles the peripheral GLP‐1 receptor. Furthermore, the presence of GLP‐1 binding sites in the circumventricular organs suggests that these may be receptors which act as the target for both peripheral blood‐borne GLP‐1 and GLP‐1 in the nervous system.
Postsynaptic Targets of Purkinje Cell Terminals in the Cerebellar and Vestibular Nuclei of the Rat
Authors: De Zeeuw C. I. , Berrebi A. S. 
Published: April 2006

AbstractThe cerebellar and vestibular nuclei consist of a heterogeneous group of inhibitory and excitatory neurons. A major proportion of the inhibitory neurons provides a GABAergic feedback to the inferior olive, while the excitatory neurons exert more direct effects on motor control via non‐olivary structures. At present it is not clear whether Purkinje cells innervate all types of neurons in the cerebellar and vestibular nuclei or whether an individual Purkinje cell axon can innervate different types of neurons. In the present study, we studied the postsynaptic targets of Purkinje cell axons in the rat using a combination of pre‐embedding immunolabelling of the Purkinje cell terminals by L7, a Purkinje cell‐specific marker, and postembedding GABA and glycine immunocytochemistry. In the cerebellar nuclei, vestibular nuclei and nucleus prepositus hypoglossi Purkinje cell terminals were found apposed to GABAergic and glycinergic neurons as well as to larger non‐GABAergic, non‐glycinergic neurons. In the cerebellar and vestibular nuclei individual Purkinje cell terminals innervated both the inhibitory and excitatory neurons. Both types of neurons were contacted not only by GABAergic Purkinje cell terminals but also by GABA‐containing terminals that were not labelled for L7 and by non‐GABAergic, non‐glycinergic terminals that formed excitatory synapses. Glycine‐containing terminals were relatively scarce (<2% of the GABA‐containing terminals) and frequently contacted the larger non‐GABAergic, non‐glycinergic neurons. To summarize, Purkinje cell axons evoke their effects through different types of neurons present in the cerebellar and vestibular nuclear complex. The observation that individual Purkinje cells can innervate both excitatory and inhibitory neurons suggests that the excitatory cerebellar output system and the inhibitory feedback to the inferior olive are controlled simultaneously.
Morphine Withdrawal Syndrome and G Protein Expression: a Study of the Time Course in the Rat Central Nervous System
Authors: Rubino Tiziana , Parenti Marco , Patrini Gabriela , Massi Paola , Parolaro Daniela 
Published: April 2006

AbstractWe followed the changes in G protein α subunit expression and levels throughout the brain during the naltrexone‐precipitated withdrawal syndrome in morphine‐dependent rats. Intraperitoneally injected naltrexone (10 mg/kg) in rats made tolerant to morphine resulted in sustained withdrawal. Additional naltrexone doses 6, 24 and 72 h later still induced a significant abstinence syndrome. At the fifth naltrexone injection (8 days later) counted signs were completely resolved but checked ones were not. Besides the behavioural modifications, opiate withdrawal affected G protein expression in the central nervous system. In situ hybridization showed that Gαs and Gαo mRNA, whose levels are increased in tolerance, changed further during opiate withdrawal. Specifically, the αs mRNA in the hypothalamus was reduced after the first naltrexone injection and reached the control level with subsequent doses. However, αo mRNA expression in the olfactory system remained elevated after repeated naltrexone injections, declining to the control value only after the fifth dose. The amounts of Gαs and Gαo protein closely followed the time course of mRNA. The relationship between behavioural and biochemical parameters is discussed, together with the regional selectivity of the modifications.
Distribution of a Brain‐specific Proteoglycan, Neurocan, and the Corresponding mRNA During the Formation of Barrels in the Rat Somatosensory Cortex
Authors: Watanabe Eiji , Aono Sachiko , Matsui Fumiko , Yamada Yasukazu , Naruse Ichiro , Oohira Atsuhiko 
Published: April 2006

AbstractNeurocan is a developmentally regulated chondroitin sulphate proteoglycan in the rat brain. In the present study, spatiotemporal patterns of expression of neurocan and the corresponding mRNA were examined in the developing cortical barrel field of the rat brain by using a monoclonal antibody that was highly specific to neurocan and a riboprobe for a portion of the mRNA. Immunohistochemical analysis revealed that neurocan was distributed throughout the cerebral cortex during early postnatal development but was excluded from the centres of cortical barrels at the time of entry and arborization of thalamocortical axons. At this developmental stage, expression of neurocan mRNA was shown by in situ hybridization to be down‐regulated in the barrel centres. When a row of whisker follicles was laser‐cauterized on postnatal day 1, the pattern of expression of neurocan was disturbed in the row of barrels that corresponded to the lesioned whisker follicles in the contralateral somatosensory cortex. From these observations, it appears that neuronal stimuli through early thalamocortical fibres from the sensory periphery cause reduced expression of neurocan mRNA in neurocan‐producing cells in the presumptive barrel centres. Our findings also suggest that the pattern of distribution of neurocan in early postnatal barrel fields may be due mainly to the down‐regulation of expression of neurocan mRNA.
Dopaminergic Agonists Have Both Presynaptic and Postsynaptic Effects on the Guinea‐pig's Medial Vestibular Nucleus Neurons
Authors: Vibert Nicolas , Serafin Mauro , Crambes Olivier , Vida1 Pierre‐Paul , Mühlethaler Michel 
Published: April 2006

AbstractA number of studies have indicated a possible interaction between dopamine and the vestibular system. Using intracellular recordings in brainstem slices, we have tested the effects of dopamine and other dopaminergic compounds on guinea‐pig medial vestibular nucleus (MVN) neurons. In normal medium, MVN neurons were depolarized by dopamine as well as by (‐)quinpirole and piribedil, which are selective D2 dopaminergic agonists. The dependence of this effect on the presence of D2 receptors was confirmed by using (‐)sulpiride, a D2 antagonist which blocked the depolarizing effect of dopamine. Dopaminergic D1 receptors were apparently not involved in this effect since a selective D1 agonist, SKF‐38393, had no effect on MVN neurons and the D1 antagonist (+) SCH‐23390 could not block the effect of dopamine. These depolarizing responses to dopamine must be due to a presynaptic action on terminals that normally release GABA spontaneously on MVN neurons, and tonically maintain them in a state of hyperpolarization. Indeed, such a spontaneous release was demonstrated to occur in the slice since application of bicuculline, a GABAA antagonist, depolarized MVNneurons in normal saline, but not in a high Mg2+/low Ca2+ solution known to block synaptic transmission. When dopamine was applied in conditions in which no GABAA‐dependent transmission could occur (either in the presence of bicuculline or in a high Mg2+/low Ca2+ solution) only a hyperpolarizing, most probably postsynaptic, effect occurred. These results indicate that dopamine might exert in vivo a significant modulatory action on the vestibular system, either by a direct action on the vestibular neurons or by modulation of GABAergic transmission.
MK‐801 Blockade of Fos and Jun Expression Following Passive Avoidance Training in the Chick
Authors: Freeman Fiona M. , Rose Steven P. R. 
Published: April 2006

AbstractTraining chicks on a one‐trial passive avoidance task results in transient up‐regulation of the N‐methyl‐d‐aspartate (NMDA) receptor in the left intermediate medial hyperstriatum ventrale (IMHV) of the forebrain 30 min post‐training. Injection of the non‐competitive NMDA receptor inhibitor, (+)‐5‐methyl‐10, 11‐dihydro‐5H‐dibenzo‐ (a.d)‐cyclohepten 5, 10‐imine maleate (MK‐801), around the time of training renders chicks amnesic for the task. Training also results in enhanced expression of the immediate early gene (IEG) c‐fos in the IMHV. To determine the relationship between NMDA receptor up‐regulation and IEG induction during memory formation we have examined the expression of Fos, Jun and their related proteins 1 h following training in the presence/absence of the putative amnestic agent MK‐801. Western blotting of IMHV samples revealed two protein bands with immunoreactivity to the Fos antibody at 47 and 54 kDa. Using an antibody to Jun, two immunoreactive bands were revealed at 39 and 54 kDa. All bands were enhanced in the left IMHV following passive avoidance training. Post‐training intraperitoneal injections of MK‐801 (75 mM) produced amnesia in ∼50% of the birds when tested 1 h after training. Injection of MK‐801 significantly attenuated expression of these proteins in birds rendered amnesic, but not in those that recalled the task. We conclude that NMDA receptor activation precedes immediate early gene expression in the memory formation cascade.
Auditory Cortex of the Rufous Horseshoe Bat: 1. Physiological Response Properties to Acoustic Stimuli and Vocalizations and the Topographical Distribution of Neurons
Authors: Radtke‐Schuller S. , Schuller G. 
Published: April 2006

AbstractThe extent and functional subdivisions of the auditory cortex in the echolocating horseshoe bat, Rhinolophus rouxi, were neurophysiologically investigated and compared to neuroarchitectural boundaries and projection fields from connectional investigations. The primary auditory field shows clear tonotopic organization with best frequencies increasing in the caudorostral direction. The frequencies near the bat's resting frequency are largely over‐represented, occupying six to 12 times more neural space per kHz than in the lower frequency range. Adjacent to the rostral high‐frequency portion of the primary cortical field, a second tonotopically organized field extends dorsally with decreasing best frequencies. Because of the reversed tonotopic gradient and the consistent responses of the neurons, the field is comparable to the anterior auditory field in other mammals. A third tonotopic trend for medium and low best frequencies is found dorsal to the caudal primary field. This area is considered to correspond to the dorsoposterior field in other mammals. Cortical neurons had different response properties and often preferences for distinct stimulus types. Narrowly tuned neurons (Q10dB < 20) were found in the rostral portion of the primary field, the anterior auditory field and in the posterior dorsal field. Neurons with double‐peaked tuning curves were absent in the primary area, but occurred throughout the dorsal fields. Vocalization elicited most effectively neurons in the anterior auditory field. Exclusive response to pure tones was found in neurons of the rostral dorsal field. Neurons preferring sinusoidal frequency modulations were located in the primary field and the anterior and posterior dorsal fields adjacent to the primary area. Linear frequency modulations optimally activated only neurons of the dorsal part of the dorsal field. Noise‐selective neurons were found in the dorsal fields bordering the primary area and the extreme caudal edge of the primary field. The data provide a survey of the functional organization of the horseshoe bat's auditory cortex in real coordinates with the support of cytoarchitectural boundaries and connectional data.
Chondroitin Sulphate Proteoglycans in the Rat Brain: Candidates for Axon Barriers of Sensory Neurons and the Possible Modification by Laminin of their Actions
Authors: Katoh‐Semba R. , Matsuda M. , Kato K. , Oohira A. 
Published: April 2006

AbstractThe addition of chondroitin sulphate proteoglycans (CSPGs), purified from the rat brain, to the culture medium of PC12D cells inhibited their proliferation and neurite outgrowth. Therefore, we investigated the effects of several extracellular components on the inhibitory actions of CSPGs on PC12D cells, as well as their immunocytochemical distribution in the rat embryo to determine whether the findings in vitro could be reproduced in vivo. Coating of the substratum with polylysine was necessary for the appearance of the inhibitory effects of brain CSPGs on PC12D cells. The additional pretreatment of polylysine‐coated dishes with laminin or fibronectin promoted the outgrowth of neurites from PC12D cells. Laminin and fibronectin, but not collagen (types I and IV) and CELL‐TAK (cell adhesion molecules), prevented the inhibitory effects of brain CSPGs in a concentration‐dependent manner. Doses producing 50% reduction by laminin (or fibronectin) of the CSPG effects were 1.5 (or 25) μg/ml for neurite outgrowth and 2.2 (or 28) μg/ml for proliferation. The ratio of dish‐attached CSPGs to laminin necessary for 50% reduction was about ∼50:l (wt/wt). Laminin from any source had the same effect. Brain CSPGs also obviously impeded the growth of fibres from dorsal root ganglion explants and primary cultured dorsal root ganglion neurons. Neurocan (a major CSPG in the brain)‐like immunoreactivity was detected in the boundary caps and roof plate in the rat embryo at 13.5 days of gestation, when DRG neurons were extending their axons to the neural tube. The distributions of laminin and tenascin appeared, respectively, to be slightly and considerably different from that of neurocan. These results suggest that brain CSPGs can generate barriers to the growth of axons from the dorsal root ganglion and that the ratio of CSPGs to laminin may be important in regulating such growth.
Molecular Cloning, Functional Expression and Pharmacological Characterization of the Human Metabotropic Glutamate Receptor Type 2
Authors: Flor P. J. , Lindauer K. , Püttner I. , Rüegg D. , Lukic S. , Knöpfel T. , Kuhn R. 
Published: April 2006

AbstractA cDNA encoding the human metabotropic glutamate receptor type 2 (hmGluR2) was isolated from human brain cDNA libraries by cross‐hybridization with rat mGluR2 probes. The deduced amino acid sequence of the human mGluR2 receptor consists of 872 residues and shows a sequence identity of 97% to the amino acid sequence of rat mGluR2. Northern blot analyses showed that hmGluR2 is widely expressed in different regions of the adult brain as well as in fetal human brain. Genomic Southern blotting localized the mGluR2 gene to human chromosome 3. Chinese hamster ovary (CHO) cells stably transfected with the cloned hmGluR2 cDNA exhibit agonist induced depression of forskolin‐stimulated cAMP accumulation. A direct comparison of CHO cells stably expressing human and rat mGluR2 with five agonists revealed the same rank order of potency [(2S,3S,4S)‐α‐(carboxycyclopropyl)‐glycine » (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid =l‐glutamate » quisqualate =l‐2‐amino‐4‐phosphonobutyric acid] and similar EC50 values for both homologous receptors. (R.S)‐a‐methyl‐4‐carboxyphenylglycine, a reported antagonist at some mGluR subtypes, reduced the depression of forskolin‐induced cAMP accumulation by (1S,3R)‐ACPD in both human and rat mGluR2.
Synergistic Trophic Actions on Rat Basal Forebrain Neurons Revealed by a Synthetic NGF/BDNF Chimaeric Molecule
Authors: Friedman W. J. , Black I. B. , Persson H. , Ibáñez C. F. 
Published: April 2006

AbstractBasal forebrain cholinergic neurons, which degenerate in Alzheimer's disease, respond to multiple trophic factors, including the neurotrophins, nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF). This dual responsiveness prompted us to investigate the effects of a synthetic chimaeric molecule, containing the active domains of both NGF and BDNF. The NGF/BDNF chimaeric factor exhibited synergistic actions, and was 100‐fold more potent than wild‐type BDNF in enhancing survival of cultured dissociated basal forebrain cholinergic neurons. This effect was apparently due to true BDNF/NGF synergy, since addition of the two wild‐type trophins simultaneously reproduced the effect of the chimaera. Synergy was selective for neurons which respond to both factors; substantia nigra dopaminergic neurons, which respond to BDNF but not NGF, exhibited no potentiation. The chimaeric factor thus revealed a synergy that may normally occur in the brain, and constitutes a potentially novel therapeutic agent with greater potency than naturally occurring individual trophins.
BDNF Produces Analgesia in the Formalin Test and Modifies Neuropeptide Levels in Rat Brain and Spinal Cord Areas Associated With Nociception
Authors: Siuciak Judith A. , Wong Vivien , Pearsall Denise , Wiegand Stanley J. , Lindsay Ronald M. 
Published: April 2006

AbstractPrevious studies have demonstrated an antinociceptive effect of brain‐derived neurotrophic factor (BDNF) following infusion into the midbrain, near the periaqueductal grey and dorsal raphe nuclei. BDNF administration attenuated the behavioural response in the tail‐flick and hot‐plate tests, two models employing a phasic, thermal high‐intensity nociceptive stimulus; the present studies extend our previous findings to include a model of moderate, continuous pain resulting from a chemical stimulus, the formalin test. Midbrain infusion of BDNF decreased the behavioural paw flinch response to subcutaneous formalin injection in both the early and late phases of the test. As our previous studies showed that BDNF‐induced analgesia was reversible by naloxone, we have examined the effects of BDNF administration on brain and spinal cord levels of neuropeptides involved in the modulation of nociceptive information, including the endogenous opioid peptides, met‐enkephalin and P‐endorphin, as well as substance P and neuropeptide Y (NPY). At the site of infusion, within the PAG and dorsal raphe, BDNF increased the level of β‐endorphin by 63%, but had no effect on substance P, metenkephalin or NPY levels. In the dorsal spinal cord, substance P (113% increase), β‐endorphin (97% increase) and NPY (64% increase) were elevated, although ventral spinal cord levels of these peptides remained unchanged. These studies demonstrate a modulatory effect of BDNF on relevant neuropeptides within areas of the brain and spinal cord involved in the processing of nociceptive information.