bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autocrine Role of Insulin‐like Growth Factor II Secretion by the Rat Choroid Plexus
Authors: Nilsson Christer , Hultberg Birthe Mørck , Gammeltoft Steen 
Published: April 2006

AbstractInsulin‐like growth factor II (IGF‐II) is expressed and secreted by the choroid plexus and has been suggested to act as a trophic factor in the adult mammalian central nervous system. The aim of the present study was to investigate whether IGF‐II has an autocrine role in the choroid plexus. Using in situ hybridization we demonstrate that IGF‐II is primarily expressed in the epithelium of adult rat choroid plexus. Conditioned medium from primary cultures of purified rat choroid plexus epithelial cells, intact choroid plexus tissue, as well as rat CSF, displaced IGF‐II binding to a 23 HMM melanoma cell line in an IGF‐II radioreceptor assay. The presence of IGF‐II and IGF binding protein‐2 in conditioned medium was shown by Western immunoblot. The mitotic activity in choroid plexus epithelial cell cultures was quantified by immunohistochemical staining of bromodeoxyuridine incorporated into cell nuclei. A monoclonal antibody towards IGF‐II inhibited cell division by 35%, while IGF‐I increased the number of stained nuclei by 75%. Basic fibroblast growth factor stimulated cell division at low concentrations, but had no effect at high concentrations. Growth hormone had no effect. We conclude that IGF‐II in the choroid plexus could have an autocrine role in the regulation of choroid plexus epithelial cell growth.
Functional Anatomy of Visuomotor Skill Learning in Human Subjects Examined with Positron Emission Tomography
Authors: Doyon Julien , Owen Adrian M. , Petrides Michael , Sziklas Viviane , Evans Alan C. 
Published: April 2006

AbstractThe present study was designed to examine patterns of regional cerebral blood flow (CBF) associated with the learning of a repeated visuomotor sequence both in the early and late phases of the acquisition process. In addition, changes in blood flow related to the implicit versus explicit aspects of learning such a skill were investigated. Fourteen normal control subjects were scanned while performing the task (i) in both early and advanced learning stages of the visuomotor sequence; (ii) after having acquired explicit knowledge of the sequences; and (iii) in two control conditions (perceptual and random sequence). Subtraction of the random condition from the highly learned condition revealed specific areas of activity in the right ventral striatum and dentate nucleus of the cerebellum. Blood flow changes in the right hemisphere were also seen in the medial posterior parietal and prestriate regions, as well as in the anterior cingulate cortex. Finally, once the subjects had acquired explicit knowledge of the embedded sequence that was presented in the highly learned condition, increased CBF activity was observed only in the mid‐ventrolateral frontal area in the right hemisphere. These findings confirm that both the striatum and the cerebellum are involved in the implicit acquisition of a visuomotor skill, especially in the advanced stages of the learning process, and furthermore that the ventrolateral prefrontal cortex contributes preferentially to the declarative aspect of this task.
Erythropoietin Gene Expression in Human, Monkey and Murine Brain
Authors: Marti Hugo H. , Wenger Roland H. , Rivas Luis A. , Straumann Urs , Oigicaylioglu Murat , Henn Volker , Yonekawa Yasuhiro , Bauer Christian , Gassmann Max 
Published: April 2006

AbstractThe haematopoietic growth factor erythropoietin is the primary regulator of mammalian erythropoiesis and is produced by the kidney and the liver in an oxygen‐dependent manner. We and others have recently demonstrated erythropoietin gene expression in the rodent brain. In this work, we show that cerebral erythropoietin gene expression is not restricted to rodents but occurs also in the primate brain. Erythropoietin mRNA was detected in biopsies from the human hippocampus, amygdala and temporal cortex and in various brain areas of the monkey Macaca mulatta. Exposure to a low level of oxygen led to elevated erythropoietin mRNA levels in the monkey brain, as did anaemia in the mouse brain. In addition, erythropoietin receptor mRNA was detected in all brain biopsies tested from man, monkey and mouse. Analysis of primary cerebral cells isolated from newborn mice revealed that astrocytes, but not microglia cells, expressed erythropoietin. When incubated at 1% oxygen, astrocytes showed >l OO‐fold time‐dependent erythropoietin mRNA accumulation, as measured with the quantitative reverse transcription‐polymerase chain reaction. The specificity of hypoxic gene induction in these cells was confirmed by quantitative Northern blot analysis showing hypoxic up‐regulation of mRNA encoding the vascular endothelial growth factor, but not of other genes. These findings demonstrate that erythropoietin and its receptor are expressed in the brain of primates as they are in rodents, and that, at least in mice, primary astrocytes are a source of cerebral erythropoietin expression which can be up‐regulated by reduced oxygenation.
Open Channel Block by Physostigmine and Procaine in Embryonic‐like Nicotinic Receptors of Mouse Muscle
Authors: Bufler J. , Franke C. , Parnas H. , Dudel J. 
Published: April 2006

AbstractEmbryonic‐like nicotinic channels were studied in mouse myotubes. Channel currents were measured by patch‐clamping outside‐out excised patches to which pulses of agonists and drugs could be applied by a liquid filament switch. The holding potential of the patches was generally around ‐40 mV. Pulses of 10‐4 M acetylcholine elicited average channel currents which reached a peak open probability, Po, peak, of 0.93 within 0.5 ms and decayed with a time constant of desensitization of 20‐80 ms. When physostigmine (10‐5 to 10‐3 M) or procaine (3 × 10‐5 to 10‐3 M) was added to the acetylcholine pulses, a fast decay component of the current appeared which shortened to a time constant of 0.5 ms for the maximal drug concentrations. The fast decay was followed by a slow one which declined in amplitude with increasing concentrations of the drugs. After the end of pulses of 10‐4 M acetylcholine plus 3 × 10‐4 M physostigmine the average current rose again, reaching a peak with ‐5 ms delay, and then decayed slowly. The amplitude of this recovery current was ‐0.4 Po, peak after 5 ms pulses and decreased with increasing pulse duration due to desensitization. The results can be quantitatively modelled based on a circular reaction scheme involving desensitization. Physostigmine and procaine bind to the open state to cause channel block. Also, the blocked channel was subject to desensitization. The rate constants of block were 6 × 10‐6 M‐1 s‐1 for physostigmine and 2 × 106 M‐1 s‐1 for procaine, and the rate of unblocking was 200 s‐1 for both blockers (at ‐40 mV and 20°C).
Ultrastructural Localization of a Voltage‐gated K+ Channel a Subunit (Kv1.2) in the Rat Cerebellum
Authors: McNamara N. M. C. , Averill S. , Wilkin G. P. , Dolly J. O. , Priestley J. V. 
Published: April 2006

AbstractA highly specific monoclonal antibody and pre‐embedding immunocytochemistry were employed to examine the distribution of the K+ channel a subunit Kv1.2 in the rat cerebellum. At the light microscopic level, the heaviest immunoreactivity was seen in the basket cell pinceau at the base of Purkinje cells, with lighter staining of basket and Golgi cell bodies and a punctate pattern in the granule cell and molecular layers. Electron microscopy was performed to identify the ultrastructural location of Kv1.2 α subunit in these labelled structures. This revealed that the labelling of the pinceau was confined to the preterminal axonal plexus, the area immediately around the Purkinje axon initial segment being relatively devoid of staining. Basket cell parent axons were not immunostained, but gave rise to heavily stained fine processes. Immunoreactivity was also seen in myelinated axons in the granule cell layer and in the medial cerebellar nucleus, the staining being most concentrated at the juxtaparanodal regions of the axons. An unusual pattern of staining was seen in some mossy fibre terminals, with staining restricted to fine protuberances of mossy fibre glomeruli. Structures contacted by these protuberances included adjoining glial processes. Immunostaining was absent from Purkinje cell bodies, dendrites, their axon initial segments and their terminals in the medial cerebellar nucleus. In this study, the a subunit Kv1.2 was localized to a number of different cell types in the cerebellum. Each neuronal type displays a distinct subcellular distribution of the subunit.
Morphological Changes in Met5‐enkephalin‐immunoreactive Synaptic Boutons in the Rat Neostriatum after Haloperidol Decanoate Treatment
Authors: Mijnster M. J. , Ingham C. A. , Meredith G. E. , Docter G. J. , Arbuthnott G. W. 
Published: April 2006

AbstractThe morphological plasticity of an identified population of synaptic boutons in the rat neostriatum was investigated 24 h (short‐term treatment) or 14 days (long‐term treatment) after administration of the depot neuroleptic, haloperidol decanoate. Specific methionine5‐enkephalin antiserum was used to label bouton profiles in the dorsal neostriatum. The size and shape of these boutons was subsequently analysed with quantitative methods at the ultrastructural level. Immunoreactive synaptic bouton profiles were found to have a larger cross‐sectional area, to be less circular in shape and to have a longer maximum diameter after long‐term neuroleptic treatment. These parameters were not significantly affected by short‐term neuroleptic treatment. The morphological parameters indicate that methionine5‐enkephalin‐immunoreactive boutons become enlarged, probably by elongating. This suggests that boutons containing methionine5‐enkephalin increase their potential synaptic efficacy in the long term after neuroleptic treatment.
Axonal Sprouting of CA1 Pyramidal Cells in Hyperexcitable Hippocampal Slices of Kainate‐treated Rats
Authors: Perez Yaël , Morin France , Beaulieu Clermont , Lacaille Jean‐Claude 
Published: April 2006

AbstractCA1 pyramidal cells become hyperexcitable following hippocampal kainate lesions. To examine if axonal sprouting contributes to this epileptiform activity, the local axonal arborization of CA1 pyramidal cells was examined after intracellular labelling with biocytin in hippocampal slices from control rats and in hyperexcitable slices obtained from rats treated with kainate (bilateral intracerebroventricular injections) 2‐4 weeks previously. Biocytin‐labelled cells with an axon that could be followed from the soma to the alveus were drawn and reconstructed with a camera lucida (15 cells from control slices and 14 cells from hyperexcitable slices). Local axonal arborizations were more extensive in cells of hyperexcitable slices. This increase in axon collaterals was generally seen in the alveus and in stratum oriens, but changes were more prominent in the latter. In stratum oriens, cells from hyperexcitable slices showed a significant increase in mean total axon length (1035 versus 373 μm in control), in mean number of branching points (6.50 versus 0.67 in control) and in mean number of segment orders per axon (3.07 versus 1.47 in control). Their first‐order axon segments were similar in length to those of control cells (236 versus 338 pm in control), but with significantly more branching points (2.86 versus 0.53 in control). Their second‐order axon segments were significantly longer (381 versus 63 μm in control) and also showed more branching points (2.71 versus 0.13 in control). Their third‐ and fourth‐order axon segments were also longer and with more branching points. Under high‐power light microscopic examination, biocytin‐labelled axonal varicosities in cells of hyperexcitable slices were often seen in close apposition with their own dendrites, presumably making synaptic contact (five of nine cells examined). No such appositions were seen in any of the control cells (seven cells examined). These results indicate that, following kainate lesions, there is sprouting of local axon collaterals of CA1 pyramidal cells in stratum oriens and in the alveus. This local increase in axon collaterals may contribute to the epileptiform activity in the CA1 area by providing recurrent excitation via newly formed synaptic, and perhaps even autaptic, contacts with pyramidal cell dendrites.
Regional Distribution of the Anticonvulsant and Behavioural Effects of Muscimol Injected into the Substantia Nigra of Rats
Authors: Shehab Safa , Simkins Marion , Dean Paul , Redgrave Peter 
Published: April 2006

AbstractPrevious anatomical investigations have reported a direct projection from substantia nigra pars lateralis to the dorsal midbrain anticonvulsant zone. The present study tested the hypothesis that the anticonvulsant properties of nigral inhibition previously attributed to substantia nigra pars reticulata were, in fact, due to the suppression of neural activity in the adjacent pars lateralis. Using the electroshock model of epilepsy, a systematic map of the anticonvulsant effects of bilateral injections of muscimol (60 ng/0.5 μI per side) into different parts of substantia nigra was constructed. Electroshock (1 s of 40 mA 50 Hz AC) was administered via ear‐clip electrodes 5 or 60 min following injections of muscimol, or 60 min after control injections of saline. To provide insight into the functional mechanisms whereby nigral inhibition might suppress tonic seizures the behavioural effects elicited by muscimol were also noted. No evidence supporting the experimental prediction was found. The most sensitive region of substantia nigra for suppressing tonic hindlimb extension was caudal pars reticulata. These data indicate a serious mismatch between the results of microinjection mapping studies and underlying patterns of anatomical connectivity. The behavioural reaction most closely associated with tonic seizure suppression was stereotyped locomotion; both were obtained maximally from caudal pars reticulata. Rostral substantia nigra was associated more with oral stereotypy, while a raised head position was observed at lateral injection sites and a lowered positioning of the head at medial locations. These data suggest that the rat substantia nigra may contain a functional organization based on a form of somatomotor topography. This organization may influence which part of the substantia nigra is most effective in suppressing seizures expressed by different muscle groups of the body.
Distinct Effects of Recombinant Tenascin‐R Domains in Neuronal Cell Functions and Identification of the Domain Interacting with the Neuronal Recognition Molecule F3/11
Authors: Xiao Zhi‐cheng , Taylor Joanne , Montag Dirk , Rougon Geneviève , Schachner Melitta 
Published: April 2006

AbstractWe have identified distinct domains of the rat extracellular matrix glycoprotein tenascin‐R using recombinant fragments of the molecule that confer neuronal cell functions. In short‐term adhesion assays (0.5 h), cerebellar neurons adhered best to the fragment representing the fibrinogen knob (FG), but also the fibronectin type Ill (FN) repeats 1‐2 and 6‐8. FG, FN1‐2 and FN3‐5 were the most repellent fragments for neuronal cell bodies. Neurites and growth cones were strongly repelled from areas coated with fragments containing the cysteine‐rich stretch and the EGF‐like domains (EGF‐L), FN1‐2, FN3‐5 and FG. Polarization of morphology of hippocampal neurons was exclusively associated with FG, while EGF‐L prevented neurite outgrowth altogether. The binding site of the neuronal receptor for tenascin‐R, the immunoglobulin superfamily adhesion molecule F3/11, was localized to EGF‐L. The combined observations show distinct, but also overlapping functions for the different tenascin‐R domains. They further suggest the existence of multiple neuronal tenascin‐R receptors which influence the response of neurons to their extracellular matrix environment.
Novelty‐related Rapid Locomotor Effects of Corticosterone in Rats
Authors: Sandi Carmen , Venero César , Guaza Carmen 
Published: April 2006

AbstractGlucocorticoids modulate brain function and behaviour through different mechanisms. Although classical effects are mediated through intracellular receptors that modulate gene transcription, recent evidence supports the existence of rapid, nongenomic steroid effects through the neuronal membrane. In this study, we explored possible rapid behavioural effects of corticosterone in the rat, which could provide a model to characterize further the mechanisms involved in rapid corticosteroid nongenomic actions. We found that a corticosterone injection, at doses (2.5 or 5 mg/kg) that mimic plasma concentrations produced by substantial stress, rapidly increases (within 7.5 min of its systemic administration) the locomotor response displayed by rats in a novel environment (activity cage). A lower dose of 1 mg/kg failed to induce this effect. In addition, corticosterone failed to increase locomotion when administered to rats that had been previously exposed to the activity cage. Corticosterone‐induced increased locomotion in a novelty situation was not counteracted by either the intracerebroventricular administration of the protein synthesis inhibitor cycloheximide, or by the intracerebroventricular administration of specific antagonists for each type of intracellular corticosteroid receptor, i.e. RU28318, a mineralocorticoid receptor antagonist and RU38486, a glucocorticoid receptor antagonist. Further studies supported the viability of the receptor antagonists to display an anti‐corticosteroid action interfering, as previously reported, with the behavioural swimming test. Therefore, the rapid actions of corticosterone in locomotor activity described here, which appear to be nongenomic, might provide a model for future research on the elucidation of the mechanisms involved in steroid‐membrane interactions.
Evidence for Modulation of DoDamine‐neuronal Function by Tachykinin NK3 Receptor Stimulation in Gerbil Mesencephalic Cell Cultures
Authors: Alonso R. , Fournier M. , Carayon P. , Petitpretre G. , Le Fur G. , Soubrié P. 
Published: April 2006

AbstractPrimary cultures of gerbil mesencephalon were used for studying the modulation exerted by tachykinin NK3 receptor activation on the activity of dopamine (DA) neurons. Dopamine neurons were identified by their ability to take up [3H]DA in a nomifensine‐dependent manner. Moreover, tyrosine hydroxylase immunohistochemistry revealed that these neurons accounted for 5–7% of the total cell population. The NK3 receptor agonists, senktide (EC50= 0.58 nM) and [MePhe7]neurokinin B (EC50= 3 nM), increased spontaneous [3H]DA release in a concentration‐dependent manner. In contrast, tested at a supramaximal concentration (10‐7 M), neither septide nor substance P were found to affect [3H]DA release. The senktide‐evoked [3H]DA release was not observed when extracellular Ca2+ was chelated, but was unaffected by nomifensine. This indicates that this increase in [3H]DA outflow resulted more from an exocytotic process than from reversal of carrier‐mediated DA uptake. Moreover, the senktide effect was unaffected by the Na+ channel blocker tetrodotoxin, a result suggesting a direct action of senktide on DA neurons. The non‐peptide NK3 receptor antagonist, SR 142801, shifted or blocked (ICs0 = 0.89 nM) the senktide‐evoked [3H]DA release, while its (‐)‐antipode, SR 142806, was 80‐fold less potent, in agreement with binding data. Selective antagonists for NK, (SR 140333) or NK2 (SR 48968) receptors failed to reduce the senktide effect. Light scanning microscopic analysis of mesencephalic cells loaded with the Ca2+ sensitive dye, fluo‐3, showed that senktide induced a rise in cytosolic Ca2+ in 8‐10% of the cell population. The senktide‐induced elevation in intracellular Ca2+ was rapid in onset and transient (at lo4 M) or more sustained with no further increase in fluorescence intensity (at 10‐7 M). The proportion of senktide‐responsive cells was not significantly modified when extracellular Ca2+ was chelated, but was reduced by 87% in the presence of SR 142801 and by 75% in cultures that were pre‐treated with the DA neurotoxin l‐methyl‐4‐phenylpyridinium. The present study shows that enhancement of spontaneous [3H]DA release and intracellular Ca2+ mobilization may be observed after NK3 receptor stimulation and that both biochemical events are likely to occur in DA neurons.
Changes in Synaptic Excitability in the Lateral Septum Associated with Contextual and Auditory Fear Conditioning in Mice
Authors: Garcia René , Jaffard Robert 
Published: April 2006

AbstractSynaptic excitability in the lateral septum (LS) was assessed electrophysiologically in freely moving mice either submitted to a painful stimulus (shock) or tested on two forms of conditioned fear: contextual conditioning and auditory cue conditioning. Only the amplitude of the N3 component of the two negative waves (N2 and N3) evoked by fimbrial stimulation displayed significant changes in these tests. Experiment 1 showed that both the painful stimulus and subsequent re‐exposure (24 h later) to the conditioning foreground context induced significant and context specific decrease in the N3 amplitude. In Experiment 2, a phasic tone (conditioned stimulus: CS) was paired (paired group) with the footshock (unconditioned stimulus: US) or not (unpaired group) and, 24 h later, animals were re‐exposed successively to the auditory cue and to the context. During the auditory cue test, only the paired group displayed significant freezing and this occurred only during presentation of the CS. In this group, however, a significant reduction in the N3 amplitude was only observed immediately after the cessation of the CS. During the context test, the percentage and time‐course of freezing across the 10 min session were similar in each group. However, in the unpaired group the N3 amplitude reduction was significant and outlasted the duration of the freezing behaviour itself. These results show that alterations in LS synaptic excitability may be dissociated from fear‐induced freezing behaviour. We suggest that LS synapses are part of a brain circuit that predict if and when the US is going to occur.
Regulation of Motoneuronal Calcitonin Gene–related Peptide (CGRP) During Axonal Growth and Neuromuscular Synaptic Plasticity Induced by Botulinum Toxin in Rats
Authors: Tarabal Olga , Calderó Jordi , Ribera Joan , Sorribas Albert , López Ricard , Molgó Jordi , Esquerda Josep E. 
Published: April 2006

AbstractThe aim of this study was to examine whether changes in rat motoneuronal calcitonin gene–related peptide (CGRP) can be correlated with axonal growth and plasticity of neuromuscular synapses. Nerve terminal outgrowth was induced by local paralysis with botulinum toxin. Normal adult soleus and tibialis anterior did not show detectable CGRP content at the motor endplates. Following botulinum toxin injection there was a progressive, transient and bimodal increase in CGRP in both motoneuron cell bodies which innervated poisoned muscles and their motor endplates. CGRP content was moderately increased 1 day after paralysis and, after an initial decline, reached a peak 20 days after injection. This was followed by a gradual decrease and a return to normal levels at the 200th day. CGRP changes in intoxicated endplates were less evident in the tibialis anterior than in the soleus muscle. The CGRP content in motoneurons was positively correlated with the degree of intramuscular nerve sprouting found by silver staining. In situ hybridization revealed an increase in CGRP mRNA in spinal cord motoneurons 20 days after toxin administration. We conclude that motoneurons regulate their CGRP in situations in which peripheral synapse remodelling and plasticity occur.