bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloning and characterization of alternative mRNA forms for the rat metabotropic glutamate receptors mGluR7 and mGluR8
Authors: Corti Corrado , Restituito Sophie , Rimland Joseph M. , Brabet Isabelle , Corsi Mauro , Pin Jean Philippe , Ferraguti Francesco 
Published: March 2003

AbstractNovel mRNA isoforms for two members of the group III metabotropic glutamate receptors (mGluRs), called mGluR7band mGluR8b, were identified from rat brain cerebral cortex and hippocampus. In both cases, the alternative splicing is generated by a similar out‐of‐frame insertion in the carboxyl‐terminus that results in the replacement of the last 16 amino acids of mGluR7 and mGluR8 by 23 and 16 different amino acids, respectively. Distribution analysis for mGluR7 and mGluR8 isoforms revealed that the two splice variants are generally coexpressed in the same brain areas. The few exceptions were the olfactory bulb, in which only the mGluR7aform could be detected by reverse transcription–polymerase chain reaction, and the lateral reticular and ambiguus nuclei, which showed only mGluR8alabelling. Despite expression in the same regions, different mRNA abundance for the two variants of each receptor were observed. When transiently coexpressed in HEK 293 cells with the phospholipase C‐activating chimeric Gαqi9‐G‐protein, thea and bforms for both receptor subtypes showed a similar pharmacological profile. The rank order of potencies for both was:dl‐amino‐4‐phosphonobutyrate > l‐serine‐O‐phosphate > glutamate. However, the agonist potencies were significantly higher for mGluR8a,bcompared with mGluR7a,b. InXenopusoocytes, glutamate evoked currents only with mGluR8 when coexpressed with Kir 3.1 and 3.4. Glutamate‐induced currents were antagonized by the group II/III antagonist (RS)‐α‐cyclopropyl‐4‐phosphonophenylglycine. In conclusion, the two isoforms of each receptor have identical pharmacological profiles when expressed in heterologous systems, despite structural differences in the carboxyl‐terminal domains.
Modification of haloperidol‐induced pattern of c‐fos expression by serotonin agonists
Authors: Tremblay Pierre‐Olivier , Gervais Julie , Rouillard Claude 
Published: March 2003

AbstractAcute challenge with clozapine and haloperidol produce different anatomical patterns of c‐fos expression in the forebrain. The pharmacological profile of atypical antipsychotics suggests that serotonin might contribute to the unique therapeutic benefits of these drugs. In order to test this possibility, we examined the abilities of 5‐HT1A and 5‐HT2A/2C agonists to modify the pattern of c‐fos expression induced by haloperidol and clozapine. Various groups of rats were pretreated with either saline, DOI, 8‐OH‐DPAT, and 8‐OH‐DPAT + DOI 30 min prior to haloperidol or clozapine administration. Rats were killed 90 min after antipsychotic administration. In saline‐pretreated rats, haloperidol produced intense Fos‐LI in all four striatal quadrants while the effect of clozapine was restricted to the medial part of the striatum. Prior administration of 8‐OH‐DPAT significantly reduced haloperidol‐induced Fos‐LI in all four striatal quadrants while DOI and 8‐OHDPAT + DOI significantly reduced Fos‐LI only in dorso‐ and ventrolateral quadrants. In the nucleus accumbens, haloperidol induced intense Fos‐LI in the core and the shell regions whereas clozapine induced c‐fos expression only in the shell. Pretreatment with 8‐OHDPAT in haloperidol treated rats reduced Fos‐LI in the core region yielding to a c‐fos pattern similar to that induced by clozapine. In the prefrontal cortex of saline‐pretreated rats, haloperidol produced a moderate c‐fos expression compared with the intense expression produced by clozapine. Pretreatment with serotonin agonists before haloperidol brought the number of FOS‐positive neurons to the same level as in clozapine treated rats. These results show the ability of 5‐HT agonists to transform the typical pattern of c‐fos expression induced by haloperidol into a pattern resembling that of clozapine.
Morphological and functional study of dwarf neurons in the rat striatum
Authors: Sancesario Giuseppe , Pisani Antonio , D'Angelo Vincenza , Calabresi Paolo , Bernardi Giorgio 
Published: March 2003

AbstractCombination of morphological and electrophysiological techniques provided data, suggesting existence in the young rat striatum of a peculiar class of neurons, the neurogliaform or dwarf neurons. Striatal neurons (n = 92), intracellularly recorded from rat brain slices, were filled (one in each slice) with the intracellular marker biocytin, to compare physiological and morphological properties in the same cell. Moreover, some neurons (n = 7) were filled with biocytin plus the fluorescent calcium indicator fura‐2, identifying cells during electrophysiological recording.Electrophysiological recordings showed that striatal neurons had different firing patterns, suggestive in most cases (n = 80) of spiny neuron class and in others (n = 12) of interneuron class. Fura‐2 injection clearly identified the body of six medium‐sized cells and of one distinctive tiny cell. This small cell, however, showed a resting membrane potential and spontaneous and evoked firing pattern characteristic of striatal interneurons. Moreover, the fura‐2 injected in such small neuron also completely filled the cell body of a near large neuron; the fura‐2 fluorescence changed synchronously in the two paired neurons after electrical stimulation of the impaled small one. Accordingly, the biocytin staining identified the morphology of the small recorded neuron as a neurogliaform‐like cell apposed to a dendrite of an aspiny neuron, suggesting that the dye injected in one neuron had diffused to the other of a different type. Furthermore, such heterologous dye coupling unexpectedly involved seven pairs of cells detected with biocytin staining (7.6% of the recorded neurons), invariably represented by a medium or large neuron on one side, and on the other side by a small (5.44 ± 0.15 × 9.14 ± 0.7 μm, mean ± SD;n = 7) neurogliaform cell, roundish in shape with few slender and short processes, usually apposed to a dendrite of the companion neurons (six out of seven). In the other cases, the biocytin staining revealed in each slice either the morphology of single spiny or aspiny neurons (80.4% of recorded neurons), or of two–three medium‐sized spiny neurons detected near to each other, suggesting that dye coupling had occurred typically between similar neurons (11.9% of the recorded neurons).These data suggest that some neurogliaform cells in the striatum of young rat can be identified as dwarf interneurons, that may be dye‐coupled with neurons of different classes.
Stimulation of benzodiazepine receptors in the dorsal hippocampus and median raphé reveals differential GABAergic control in two animal tests of anxiety
Authors: Gonzalez Luis E. , Ouagazzal Abdel‐Mouttalib , File Sandra E. 
Published: March 2003

AbstractThe effects of pharmacological challenges to the benzodiazepine receptors in the dorsal hippocampus and median raphé nucleus were investigated in the social interaction and the elevated plus‐maze tests of anxiety in rats. In the social interaction test, bilateral administration of midazolam (1 and 2 μg), into the dorsal hippocampus had anxiolytic effects; flumazenil (500 ng) was silent, but was able to antagonize the anxiolytic effects of midazolam (2 μg). In the social interaction test, midazolam was also anxiolytic when infused into the median raphé nucleus; flumazenil (100 and 500 ng) increased locomotor activity, but did not change anxiety measures. As an anatomical control, midazolam (1 and 2 μg) was infused into the adjacent pontine reticular nucleus, and was without effect. In contrast to the social interaction test, local infusion of midazolam (1 and 2 μg) and flumazenil (100 and 500 ng) into either the dorsal hippocampus or the median raphé nucleus failed to change anxiety measures in the elevated plus‐maze (trials 1 and 2). These results show that stimulation of the benzodiazepine receptors in the hippocampus or the median raphé nucleus leads to anxiolytic effects in the social interaction test, but not in the elevated plus‐maze. It would therefore appear that the two tests detect different types of anxiety that are differentially modulated by GABAA‐benzodiazepine receptors in the dorsal hippocampus and the median raphé nucleus.
Regions in the human brain activated by simultaneous orientation discrimination: a study with positron emission tomography
Authors: Dupont Patrick , Vogels Rufin , Vandenberghe Rik , Rosier Annemie , Cornette Luc , Bormans Guy , Mortelmans Luc , Orban Guy A. 
Published: March 2003

AbstractIn order to compare regional cerebral activity involved in simultaneous as opposed to successive orientation discrimination, we used positron emission tomography to measure regional cerebral blood flow, in two threefold sets of conditions, in a large number of subjects. The first such triad involved simultaneous orientation discrimination, orientation identification and detection, with all tasks using the same pair of gratings. The second triad consisted of successive orientation discrimination with its corresponding identification and detection tasks. Comparisons between tasks within each triad isolate attention to orientation and, respectively, spatial or temporal comparison. The subtraction of detection from simultaneous discrimination revealed activation of right fusiform, right lingual, left precentral, left cingulate and left temporal cortex, in addition to right insula, cerebellum and left thalamus. Only the fusiform, insular and precentral activations remained when the corresponding identification was subtracted from simultaneous discrimination. In contrast, most of the non‐visual activation sites remained when simultaneous discrimination was compared with successive discrimination, which also revealed a left lingual activation. These experiments provide further evidence for task‐dependent processing in the human visual system and suggest that the right fusiform cortex is involved in spatial as much as temporal comparisons.
Behavioural characterization of interleukin‐6 overexpressing or deficient mice during agonistic encounters
Authors: Alleva Enrico , Cirulli Francesca , Bianchi Mauro , Bondiolotti Gian Pietro , Chiarotti Flavia , De Acetis Luigi , Panerai Alberto E. 
Published: March 2003

AbstractInterleukin‐6 (IL‐6) is a cytokine released by activated immune cells which has been shown to affect brain function. In this experiment aggressive and affiliative behaviour exhibited during agonistic encounters by transgenic male mice either not expressing (IL‐6 –/–) or overexpressing (NSE‐hIL‐6) IL‐6 in the central nervous system was investigated. All subjects were isolated for 24 days before the aggressive encounter and were 52 days old at the time of testing. Subjects were placed for 5 consecutive days in a neutral cage for 15 min with an opponent of the Balb/c strain that had been previously isolated for the same amount of time. The first and the last test sessions were videotaped to evaluate the first approach and the establishment of the social role, respectively. A number of behavioural categories were later scored. When compared with wild‐type controls,IL‐6 –/– mice showed a higher degree of aggressive behaviour as indicated by a higher frequency of Offensive Upright Posture, an effect more pronounced on the fifth encounter. On the contrary, NSE‐hIL‐6 subjects showed a tendency to be more involved in affiliative‐type social interactions, displaying a higher frequency and duration of behaviours such as Anogenital, Nose or Body Sniff. IL‐6 –/– mice showed a clear tendency to exhibit less affiliative interactions compared with their controls while dopamine levels were found to be modified in a number of brain regions in these mice.Overall, these data suggest that IL‐6 affects both aggressive and affiliative‐type interactions, although the behaviour of the NSE‐hIL‐6 subjects was less affected than that of the IL‐6 –/– group. The effects of the genetic background of the animal in screening the outcome of gene manipulations on behaviour are also discussed.
Growth/differentiation factor 5 and glial cell line‐derived neurotrophic factor enhance survival and function of dopaminergic grafts in a rat model of Parkinson's disease
Authors: Sullivan Aideen M. , Pohl Jens , Blunt Stavia B. 
Published: March 2003

AbstractGrowth/differentiation factor 5 is a member of the transforming growth factor β superfamily, which has neurotrophic and neuroprotective effects on dopaminergic neurons both in vitro and in vivo. Here we investigate the effects of growth/differentiation factor 5 on foetal mesencephalic grafts transplanted into a rat model of Parkinson's disease, and compare them with those of glial cell line‐derived neurotrophic factor. Mesencephalic tissue was suspended in solutions containing either growth/differentiation factor 5 or glial cell line‐derived neurotrophic factor prior to transplantation into the left striatum of rats with 6‐hydroxydopamine lesions of the left medial forebrain bundle. Both proteins enhanced graft‐induced compensation of amphetamine‐stimulated rotations. Positron emission tomography studies showed that both neurotrophins increased graft‐induced recovery of striatal binding of [11C]RTI‐121, a marker for dopaminergic nerve terminals. Post mortem analysis at 8 weeks after transplantation showed that both neurotrophins significantly increased the survival of grafted dopaminergic neurons. This study shows that growth/differentiation factor 5 is at least as effective as glial cell line‐derived neurotrophic factor in enhancing the survival and functional activity of mesencephalic grafts, and thus is an important candidate for use in the treatment of Parkinson's disease.
Activated microglial cells migrate towards sites of excitotoxic neuronal injury inside organotypic hippocampal slice cultures
Authors: Heppner Frank L. , Skutella Thomas , Hailer Nils P. , Haas Dorit , Nitsch Robert 
Published: March 2003

AbstractThe aim of this study was to analyse microglial reactions to excitotoxic N‐methyl‐d‐aspartic acid (NMDA)‐induced degeneration of rat dentate and hippocampal neurons in vitro. We used a migration model combining the techniques of microglial single cell culture and organotypic hippocampal slice culture (OHSC). Site‐specific oxidative damage in OHSCs was induced by pretreatment with 50 μm NMDA. Neuronal injury determined by propidium iodide (PI) uptake included the hippocampal cell layers of the dentate gyrus (DG) and the cornu ammonis (CA). Fluorescence‐prelabelled microglial cells with ameboid morphology were transferred onto the OHSC and migrated predominantly to the prelesioned cell layers of DG and CA when compared with unlesioned areas of the OHSC. In NMDA pretreated slices, microglial cells clustered around degenerating granule cells in the DG and pyramidal cells in the CA. This effect was significantly inhibited in unlesioned slice cultures and in NMDA‐exposed cultures that were pretreated with the NMDA‐antagonist MK‐801. Our observations suggest that microglia – attracted by the presence of stimuli provided by NMDA‐induced neuronal death – migrate specifically towards these lesioned neurons.
Subcellular and subsynaptic distribution of the NR1 subunit of the NMDA receptor in the neostriatum and globus pallidus of the rat: co‐localization at synapses with the GluR2/3 subunit of the AMPA receptor
Authors: Bernard Véronique , Bolam J. Paul 
Published: March 2003

AbstractGlutamatergic neurotransmission in the neostriatum and the globus pallidus is mediated through NMDA‐type as well as other glutamate receptors and is critical in the expression of basal ganglia function. In order to characterize the cellular, subcellular and subsynaptic localization of NMDA receptors in the neostriatum and globus pallidus, multiple immunocytochemical techniques were applied using antibodies that recognize the NR1 subunit of the NMDA receptor. In order to determine the spatial relationship between NMDA receptors and AMPA receptors, double labelling was performed with the NR1 antibodies and an antibody that recognizes the GluR2 and 3 subunits of the AMPA receptor.In the neostriatum all neurons with characteristics of spiny projection neurons, some interneurons and many dendrites and spines were immunoreactive for NR1. In the globus pallidus most perikarya and many dendritic processes were immunopositive. Immunogold methods revealed that most NR1 labelling is associated with asymmetrical synapses and, like the labelling for GluR2/3, is evenly spread across the synapse. Double immunolabelling revealed that in neostriatum, over 80% of NR1‐positive axospinous synapses are also positive for GluR2/3. In the globus pallidus most NR1‐positive synapses are positive for GluR2/3. In both regions many synapses labelled only for GluR2/3 were also detected.These results, together with previous data, suggest that NMDA and AMPA receptor subunits are expressed by the same neurons in the neostriatum and globus pallidus and that NMDA and AMPA receptors are, at least in part, colocalized at individual asymmetrical synapses. The synaptic responses to glutamate in these regions are thus likely be mediated by both AMPA and NMDA receptors at the level of individual synapses.
Continuous blockade of brain glucocorticoid receptors facilitates spatial learning and memory in rats
Authors: Oitzl Melly S. , Fluttert Marc , Sutanto Win , De Kloet E. Ron 
Published: March 2003

AbstractPreviously, a corticosterone surge associated with a learning task was shown to facilitate cognitive processes through brain glucocorticoid receptors (GR) while chronic overexposure to this stress hormone impaired cognition. In the present study we tested the hypothesis that opposing effects on learning and memory might also occur after either phasic or continuous blockade of brain GR by intracerebroventricular (i.c.v.) administration of the GR antagonist RU38486 (aGR). We used a Morris water maze procedure to assess spatial learning and memory abilities in male Wistar rats. The effect of phasic brain GR blockade was studied following daily pretraining administration of 10 and 100 ng/μL aGR i.c.v. on 3 consecutive days. This repetitive aGR treatment impaired spatial learning and memory dose‐dependently in comparison with vehicle controls. For continuous brain GR blockade, animals received an i.c.v. infusion of aGR (10 and 100 ng/0.5 μL per h or vehicle) over 10 days. Infusion of 100 ng aGR per hour resulted in a long‐lasting facilitation of spatial performance. The 10 ng aGR infusion also caused initially a facilitating effect, which was, however, transient and performance became impaired during retest. Possible anxiolytic properties of the drugs were excluded in view of the animals' behaviour in the elevated plus maze. Both doses of aGR infusion reduced the number of mineralocorticoid receptors in the hippocampus, but only the high dose of aGR resulted in a significant reduction of available GR sites. In conclusion, continuous administration of GR antagonist improves cognitive function, while phasic blockade of brain GR function causes a cognitive deficit.
Neurotrophic ACTH4–9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis
Authors: Duckers H. J. , Van Dokkum R. P. , Verhaagen J. , Van Luijtelaar E. L. , Coenen A. M. , Da Silva F. H. Lopes , Gispen W. H. 
Published: March 2003

AbstractChronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best defined electrophysiological abnormalities are the changes in event‐related potentials, in particular evoked potentials involving the spinal cord, i.e. motor and sensory evoked potentials. Less familiar are the changes observed in the electroencephalogram of CEAE‐affected animals, which are also encountered in the human equivalent, MS. In the present experiment we evaluated the therapeutic value of a neurotrophic peptide treatment [H‐Met(O2)‐Glu‐His‐Phe‐d‐Lys‐Phe‐OH, an ACTH4–9 analogue] and its effect on the delayed flash visual evoked potentials (VEP) and power spectra of the electroencephalogram, during a 17‐week follow‐up of CEAE. CEAE animals treated with the neurotrophic peptide were protected against the development of neurological symptoms during the course of the demyelinating syndrome. VEPs of animals suffering from CEAE showed a delay of the latencies of the late components which was significantly counteracted by peptide treatment. The peak‐to‐peak amplitude of the VEP afterdischarge recorded from CEAE animals was significantly increased during the course of CEAE and correlated closely with the progression of the myelinopathy. Furthermore, CEAE animals showed an increase of electroencephalogram (EEG) beta activity of up to 500% as compared with the age‐matched control group. This increase in beta power mainly consisted of a prevailing 20–21 Hz peak, a frequency that normally is not dominant in control EEG recordings of the rat during passive wakefulness. All these electrophysiological phenomena were absent in ACTH4–9 analogue‐treated animals. The present findings underscore the potential importance of a neurotrophic peptide treatment in the pharmacotherapy of central demyelinating syndromes, and possibly of MS.
Direction discrimination of moving gratings and plaids and coherence in dot displays without primary visual cortex (V1)
Authors: Benson Philip J. , Guo Kun , Blakemore Colin 
Published: March 2003

AbstractWe present new experimental observations of G.Y., a well‐tested patient with unilateral loss of primary visual cortex. We stimulated G.Y.'s blind hemifield using first‐ and second‐order motion stimuli at velocities around psychophysical threshold. Using a dual response paradigm (awareness level of visual motion, motion direction discrimination) psychophysical performance improved with increasing velocity and dot coherence. We were also able to influence directly G.Y.'s performance for the better and at will, by placing the emphasis solely on direction discrimination. In the absence of V1, graduated detection and discrimination of stimuli known to activate both V1 and extrastriate motion areas MT/V5 and MST is still possible. These results are in line with residual visual processing but did not show evidence of unconscious processing of motion stimuli characteristic of ‘blindsight’.
Direct glutamate‐mediated presynaptic inhibition of sensory afferents by the postsynaptic motor neurons
Authors: Cattaert Daniel , Ray Didier Le 
Published: March 2003

AbstractAn in vitro preparation of the crayfish central nervous system was used to study a negative feedback control exerted by the glutamatergic motor neurons (MNs) on to their presynaptic cholinergic sensory afferents. This negative control consists in small amplitude, slowly developing depolarizations of the primary afferents (sdPADs) strictly timed with MN bursts. They were not blocked by picrotoxin, but were sensitive to glutamate non‐N‐methyl‐d‐aspartate (NMDA) antagonists. Intracellular recordings were performed within thin branches of sensory terminals while electrical antidromic stimulation were applied to the motor nerves, or while glutamate (the MN neurotransmitter) was pressure‐applied close to the recording site. Electrical motor nerve stimulations and glutamate pressure application had similar effects on to sensory terminals issued from the coxo‐basipodite chordotonal organ (CBTs): like sdPADs, both stimulation‐induced depolarizations were picrotoxin‐resistant and were dramatically reduced by non‐NMDA antagonist bath application. These results indicate that sdPADs are likely directly produced by MNs during locomotor activity. A functional scheme is proposed.