bluuebunny/crossref_metadata_2025_split huggingface dataset:
The dopaminergic hyper‐responsiveness of the shell of the nucleus accumbens is hormone‐dependent
Authors: Barrot Michel , Marinelli Michela , Abrous Djoher Nora , Rougé‐Pont Françoise , Le Moal Michel , Piazza Pier Vincenzo 
Published: March 2003

AbstractThe dopaminergic projection to the shell of the nucleus accumbens is the most reactive to stress, reward and drugs of abuse and this subregion of the nucleus accumbens is also considered a target of therapeutic effects of atypical antipsychotic drugs (APD). In this report we show, by means of in vivo microdialysis and Fos immunohistochemistry, that the hyper‐responsiveness which characterizes the dopaminergic transmission to the shell is dependent on glucocorticoid hormones. In Sprague‐Dawley rats, after suppression of endogenous glucocorticoids by adrenalectomy, extracellular dopamine levels selectively decreased in the shell, whilst they remained unchanged in the core. This effect was observed in basal conditions, after a mild stress (vehicle injection), as well as after subcutaneous administration of morphine (2 mg/kg, s.c.) or intraperitoneal injection of cocaine (15 mg/kg, i.p.). The decrease in dopamine observed in the shell had a postsynaptic impact, as shown by less induction of Fos‐like proteins selectively in the shell in response to cocaine. However, the induction of Fos‐like proteins by the full D1 agonist SKF82958 (1.5 mg/kg, i.p.) remained unchanged after adrenalectomy, suggesting that the changes in Fos expression after cocaine injection were likely to depend on changes in extracellular dopamine levels rather than on changes in postsynaptic sensitivity to dopamine. The effects of adrenalectomy were glucocorticoid‐specific given that they were prevented by corticosterone treatment. This anatomical specificity in the control of neuronal activity by a hormonal input highlights the role of steroid hormones in shaping the functional activity of the brain.
Depolarizing stimulation upregulates GA‐binding protein in neurons: a transcription factor involved in the bigenomic expression of cytochrome oxidase subunits
Authors: Zhang Chenyang , Wong‐Riley Margaret T. T. 
Published: March 2003

AbstractNeurons are unique in having dendrites that extend far away from their cell bodies. Mitochondria located in the dendrites can be separated from the nucleus for long distances. The mechanism of bigenomic coordination is of particular importance to cytochrome oxidase (CO), which has subunits that are encoded in both the nuclear and mitochondrial DNA. GA‐binding protein (GABP) is a transcription factor that is required for the promoter activity of mitochondrial transcription factor A as well as several nuclear‐encoded CO subunits. Thus, GABP may play a key role in coordinating the transcription of both mitochondrial and nuclear‐encoded subunits of CO. The goal of the present study was to determine if GABP was expressed in neurons and whether and how it responded to increased neuronal activity. Using primary neuronal cultures, the β‐subunit of GABP was localized immunocytochemically to both the cytoplasm and the nucleus, whereas the α‐subunit was expressed mainly in the nucleus. In KCl‐treated cultures, immunoreactivity for both α‐ and β‐subunits was significantly increased in the nucleus compared with untreated sister cultures. The induction of GABP preceded that of CO gene expression from the two genomes, which, in turn, preceded that of CO activity. Thus, our data suggest that neuronal activity regulates subunit concentrations of GABP in the nucleus, and GABP may be a critical sensor of changes in neuronal activity. Our data are also consistent with the postulated role of GABP as a coordinator of both mitochondrial and nuclear transcription for subunits of CO in neurons.
Outgrowth‐promoting molecules in the adult hippocampus after perforant path lesion
Authors: Savaskan Nicolai E. , Skutella Thomas , Bräuer Anja U. , Plaschke Martina , Ninnemann Olaf , Nitsch Robert 
Published: March 2003

AbstractLesion‐induced neuronal plasticity in the adult central nervous system of higher vertebrates appears to be controlled by region‐ and layer‐specific molecules. In this study we demonstrate that membrane‐bound hippocampal outgrowth‐promoting molecules, as present during the development of the entorhino‐hippocampal system and absent or masked in the adult hippocampus, appear 10 days after transection of the perforant pathway. We used an outgrowth preference assay to analyse the outgrowth preference of axons from postnatal entorhinal explants on alternating membrane lanes obtained from hippocampus deafferented from its entorhinal input taken 4, 10, 20, 30 and 80 days post‐lesion and from adult control hippocampus. Neurites from the entorhinal cortex preferred to extend axons on hippocampal membranes disconnected from their entorhinal input for 10 days in comparison with membranes obtained from unlesioned adult animals. Membranes obtained from hippocampi disconnected from their entorhinal input for 10 days were equally as attractive for growing entorhinal cortex (EC) axons as membranes from early postnatal hippocampi. Further analysis of membrane properties in an outgrowth length assay showed that entorhinal axons extended significantly longer on stripes of lesioned hippocampal membranes in comparison with unlesioned hippocampal membranes. This effect was most prominent 10 days after lesion, a time point at which axonal sprouting and reactive synaptogenesis are at their peak. Phospholipase treatment of membranes obtained from unlesioned hippocampi of adult animals strongly promoted the outgrowth length of entorhinal axons on these membranes but did not affect their outgrowth preference for deafferented hippocampal membranes. Our results indicate that membrane‐bound outgrowth‐promoting molecules are reactivated in the adult hippocampus following transection of the perforant pathway, and that neonatal entorhinal axons are able to respond to these molecules. These findings support the hypothesis of a temporal accessibility of membrane‐bound factors governing the layer‐specific sprouting of remaining axons following perforant path lesion in vivo.
Bicuculline injections into the rostral and caudal motor thalamus of the monkey induce different types of dystonia
Authors: Guehl D. , Burbaud P. , Boraud T. , Bioulac B. 
Published: March 2003

AbstractThe pathophysiology of dystonia remains unclear in comparison with other movement disorders. Recent data suggest that there may exist in dystonia an increased thalamic drive to the mesial premotor cortex. To test this hypothesis, we induced overactivity of the motor thalamus by injecting a GABA‐A (γ‐aminobutyric acid) antagonist (bicuculline) into the rostral (pallidal) and caudal (cerebellar) ventrolateral nuclei of the thalamus in both hemispheres of one monkey. Dystonic postures were observed in the contralateral limbs and axis. Electromyographic recordings revealed bursts of muscular activation with co‐contractions during spontaneous dystonic movements and alterations in muscular patterns during sequential visually guided arm movements. The type of dystonia depended on the site of injections. Rostral thalamic injections induced more severe dystonic postures, whereas myoclonic jerks predominated following caudal injections. We conclude that these two distinct clinical patterns, which are frequently associated in humans, are probably due to a dysfunctioning of segregated thalamic projections to the supplementary motor area (from the rostral part) and to the primary motor cortex (from the caudal part).
Neuronal distribution and functional characterization of the calcium channel α2δ‐2 subunit
Authors: Hobom M. , Dai S. , Marais E. , Lacinova L. , Hofmann F. , Klugbauer N. 
Published: March 2003

AbstractThe auxiliary calcium channel α2δ subunit comprises a family of three genes, α2δ‐1 to 3, which are expressed in a tissue‐specific manner. α2δ‐2 mRNA is found in the heart, skeletal muscle, brain, kidney, liver and pancreas. We report here for the first time the identification and functional characterization of α2δ‐2 splice variants and their mRNA distribution in the mouse brain. The splice variants differ in the α2 and δ protein by eight and three amino acid residues, respectively, and are differentially expressed in cardiac tissue and human medullary thyroid carcinoma (hMTC) cells. In situ hybridization of mouse brain sections revealed the highest expression of α2δ‐2 mRNA in the Purkinje cell layer of the cerebellum, habenulae and septal nuclei, and a lower expression in the cerebral cortex, olfactory bulb, thalamic and hypothalamic nuclei, as well as the inferior and superior colliculus. As the in situ data did not suggest a specific colocalization with any α1 subunit, coexpression studies of α2δ‐2 were carried out either with the high‐voltage‐gated calcium channels, α1C, α1E or α1A, or with the low‐voltage‐gated calcium channel, α1G. Coexpression of α2δ‐2 increased the current density, shifted the voltage dependence of channel activation and inactivation of α1C, α1E and α1A subunits in a hyperpolarizing direction, and accelerated the decay and shifted the steady‐state inactivation of the α1G current.
Opioids intrinsically inhibit the genesis of mouse cerebellar granule neuron precursors in vitro: differential impact of μ and δ receptor activation on proliferation and neurite elongation
Authors: Hauser Kurt F. , Houdi Abdulghani A. , Turbek Carol S. , Elde Robert P. , Iii William Maxson 
Published: March 2003

AbstractAlthough opioids are known to affect neurogenesis in vivo, it is uncertain the extent to which opioids directly or indirectly affect the proliferation, differentiation or death of neuronal precursors. To address these questions, the intrinsic role of the opioid system in neurogenesis was systematically explored in cerebellar external granular layer (EGL) neuronal precursors isolated from postnatal mice and maintained in vitro. Isolated neuronal precursors expressed proenkephalin‐derived peptides, as well as specific μ and δ, but negligible κ, opioid receptors. The developmental effects of opioids were highly selective. Morphine‐induced μ receptor activation inhibited DNA synthesis, while a preferential δ2‐receptor agonist ([d‐Ala2]‐deltorphin II) or Met‐enkephalin, but not the δ1 agonist [d‐Pen2, d‐Pen5]‐enkephalin, inhibited differentiation within the same neuronal population. If similar patterns occur in the developing cerebellum, spatiotemporal differences in endogenous μ and δ opioid ligand–receptor interactions may coordinate distinct aspects of granule neuron maturation. The data additionally suggest that perinatal exposure to opiate drugs of abuse directly interfere with cerebellar maturation by disrupting normal opioid signalling and inhibiting the proliferation of granule neuron precursors.
Evidence for nonvesicular nitric oxide release evoked by nerve activation
Authors: Olgart Caroline , Gustafsson Lars E. , Wiklund N. Peter 
Published: March 2003

AbstractThe gaseous nature of nitric oxide (NO) has led to the general assumption that its release from neurons during nerve stimulation is independent of vesicular storage. However, recent findings have shown that NO can exist intracellularly as part of more stable bioactive molecules, suggesting that the role of vesicular exocytosis for NO release cannot be excluded simply based on the chemical nature of NO itself. We have used botulinum toxin B (BTX B) to directly address the role of vesicular exocytosis for NO release. BTX B cleaves the synaptic vesicle protein synaptobrevin/VAMP, and by this inhibits Ca++‐mediated exocytic release of neurotransmitters. As a target organ we used the guinea‐pig enteric nervous system, which innervates the gastrointestinal tract, and in which both classical neurotransmitters as well as NO are released and influence smooth muscle activity. As expected, BTX B (0.1 μm) blocked the nerve stimulation‐induced cholinergic and tachykininergic smooth muscle contractions, and markedly inhibited the nerve stimulation‐evoked release of [3H]‐choline. In contrast, BTX B (0.1 μm) had no effect on nerve stimulation‐evoked relaxations, which were equally inhibited by an NO‐synthase inhibitor as well as by a selective inhibitor of soluble guanylyl cyclase. In addition, nerve stimulation‐evoked NO synthase‐dependent outflow of NO/NO2– was unaffected by BTX B (0.1 μm). These findings suggest that the neuronal release of endogenous NO is independent of intact synaptobrevin/VAMP, and therefore provide further evidence that nerve‐mediated release of further NO is nonvesicular.
The human eye expresses high levels of CB1 cannabinoid receptor mRNA and protein
Authors: Porcella Anna , Maxia Chiara , Gessa Gian Luigi , Pani Luca 
Published: March 2003

AbstractWe used reverse transcriptase polymerase chain reaction to detect the expression of the central and peripheral cannabinoid receptors (CB1 and CB2, respectively) mRNA, and Western blotting to show the presence of the CB1 protein in subregions of the human eye. CB2 mRNA transcripts were undetectable, while levels of CB1 mRNA were significantly expressed in the human retina (25.8 ± 2.46%), ciliary body (210 ± 11.55%) and iris (62.7 ± 5.94%) when compared with those of the normalizing reference gene β2 microglobulin. The CB1 gene encodes a functional protein which is detected in its glycosylated (63 kDa) and unglycosylated (54 kDa) form in the same areas by a specific purified antibody raised against the amino terminus (residues 1–77) of the CB1 receptor. These results further support the proposed role of the CB1 receptor in controlling intraocular pressure, helping to explain the antiglaucoma properties of marijuana.
Long‐term potentiation of primary afferent neurotransmission at trigeminal synapses of juvenile rats
Authors: Hamba Michiko , Onodera Kayoko , Takahashi Tomoyuki 
Published: March 2003

AbstractPrimary afferent monosynaptic and polysynaptic excitatory postsynaptic currents (EPSCs) were recorded from brainstem trigeminal neurons by stimulation of the mandibular nerve attached to the brainstem preparation of juvenile rats. A high‐frequency conditioning stimulus induced long‐term potentiation (LTP) of high‐threshold EPSCs in the majority of trigeminal caudal neurons in substantia gelatinosa, where both A‐ and C‐fibres terminate. However, the same conditioning stimulus did not potentiate low‐threshold EPSCs in caudal neurons or EPSCs recorded from neurons in the middle part of trigeminal interpolar nucleus, where C‐fibres rarely terminate. LTP in caudal neurons could be induced after blocking N‐methyl‐ d‐aspartate (NMDA) receptors with D(–)‐2‐amino‐5‐phosphonopentanoic acid (D‐AP5, 50 μm), after postsynaptic loading of the Ca2+ chelator BAPTA (10 mm), or even after completely blocking excitatory transmission with kynurenic acid during conditioning. However, LTP was blocked by the metabotropic glutamate receptor antagonist (+)‐α‐methyl‐4‐carboxyphenylglycine (1 mm). We suggest that LTP of the trigeminal primary afferent EPSCs is induced preferentially in the C‐fibre inputs and that the induction mechanism involves metabotropic glutamate receptors, possibly at the presynaptic terminals.
Correlation between gene functions and developmental expression patterns in the mouse cerebellum
Authors: Matoba Ryo , Kato Kikuya , Kurooka Chika , Maruyama Chiyuri , Sakakibara Yoshimasa , Matsubara Kenichi 
Published: March 2003

AbstractQuantitative changes of 419 gene transcripts during postnatal mouse cerebellar development were accurately determined with a novel polymerase chain reaction (PCR)‐based technique. About 70% of the genes showed differences in expression levels, and the magnitude of difference was relatively small. By hierarchic cluster analysis of developmental expression patterns, the genes were categorized into 19 clusters, which were subsequently assembled into four major groups: group 1, with elevation of gene expression throughout the time course; group 2, with relatively unchanged levels; group 3, with transiently high expression at ∼ 12 days; and group 4, with highest expression at ∼ 4 days. Genes related to brain functions were segregated into several clusters of group 1 and group 3: the same clusters in which cerebellum‐specific genes were also segregated. Genes for protein synthesis belonged to group 4. Genes with housekeeping functions belonged to group 2. Western blotting analysis of representative protein products of each group revealed correlation with the mRNA level for those belonging to group 1 and group 4, but not necessarily in the other groups. The close correlation of algorithmically categorized temporal expression patterns of genes with their functions will be useful for estimating the functions of thousands of novel genes.
Layer‐specific immunocytochemical localization of GABABR1a and GABABR1b receptors in the rat piriform cortex
Authors: Princivalle Alessandra , Spreafico Roberto , Bowery Norman , De Curtis Marco 
Published: March 2003

AbstractA peculiar, layer‐segregated immunoreactive distribution of GABABR1a and GABABR1b receptor antibodies is present in the piriform cortex of adult rats. The GABABR1a antibody selectively marked the neuropile in layer Ia, where afferent olfactory fibres and intrinsic GABAergic (γ‐aminobutyric acid) axons terminate on the distal apical dendrites of pyramidal neurons. The GABABR1b antibody was detected in the soma and the large basal dendrites of layer II and III neurons. The pattern of distribution observed supports the hypothesis that (presynaptic) GABABR1a receptors in the superficial molecular layer modulate neurotransmitter release in a feedforward synaptic circuit, whereas GABABR1b (postsynaptic) receptors mediate feedback inhibitory potentials on principal cells.
Orientation discrimination of objects and gratings compared: an fMRI study
Authors: Faillenot Isabelle , Sunaert Stefan , Van Hecke Paul , Orban Guy A. 
Published: March 2003

AbstractWe used functional magnetic resonance imaging to compare the human brain regions involved in orientation discrimination of two‐dimensional (2D) objects and gratings. The orientation discrimination tasks, identification and successive discrimination, were contrasted to a dimming detection control condition with identical retinal input. Regions involved in orientation discrimination were very similar for the two types of tasks and for the two types of stimuli and both belonged to the dorsal and ventral visual pathways. They included posterior occipital, lingual, posterior fusiform, inferior temporal, dorsal intraparietal and medial parietal regions. The main difference between the two types of stimuli was a larger activation of precuneus when 2D objects were used compared to gratings. The main difference between discrimination tasks was an enhanced activity, at the group level, in superior frontal sulcus in identification compared to successive discrimination, and at least at the single subject level, a larger activity in right fusiform cortex in successive discriminations compared to identification. Thus, in contradiction to generally accepted views, orientation discrimination of gratings and objects involve largely similar networks including both ventral and dorsal visual regions.
Differential expression of fibroblast growth factor‐2 and fibroblast growth factor receptor 1 in a scarring and nonscarring model of CNS injury in the rat
Authors: Smith Conrad , Berry Martin , Clarke Wendy E. , Logan Ann 
Published: March 2003

AbstractInjury to the adult brain results in abortive axon regeneration and the deposition of a dense fibrous glial scar. Therapeutic strategies to promote postinjury axon regeneration are likely to require antiscarring strategies. In neonatal brain wounds, scar material is not laid down and axons grow across the lesion site, either by de novo growth or regeneration. To achieve the therapeutic goal of recapitulating the nonscarring neonatal response in the injured adult, an understanding of how ontogenic differences in scarring reflect developmental diversities in the trophic response to injury is required. Fibrobast growth factor‐2 (FGF‐2) expression is developmentally regulated and has been implicated as a regulator of the wounding response of the adult rat central nervous system. We have investigated the expression of FGF‐2 and fibroblast growth factor receptor 1 (FGFR1) after penetrating lesions to the cerebral cortex of 5 days post partum (dpp) (nonscarring) and 16 dpp and adult (scarring) rats. In situ hybridization, immunohistochemistry and Western blotting showed robust and sustained increases in FGF‐2 and FGFR1 mRNA and protein in reactive astrocytes around the lesion in scarring rats, a response that was attenuated substantially in the nonscarring neonate. These results demonstrate that changes in astrocyte FGF‐2 and FGFR1 expression are coincident with the establishment of a mature pattern of glial scarring after injury in the maturing central nervous system, but it is premature to infer a causal relationship without further experiments.
Input‐dependent synaptic targeting of α2‐subunit‐containing GABAA receptors in synapses of hippocampal pyramidal cells of the rat
Authors: Nyíri Gábor , Freund Tamás F. , Somogyi Péter 
Published: March 2003

AbstractPyramidal cells, expressing at least 14 subunits of the heteropentameric GABAA receptor, receive GABAergic input on their soma and proximal dendrites from basket cells, activating GABAA receptors and containing either parvalbumin or cholecystokinin and vasoactive intestinal polypeptide. The properties of GABAA receptors are determined by the subunit composition, and synaptic receptor content governs the effect of the presynaptic neuron. Using a quantitative electron microscopic immunogold technique, we tested whether the synapses formed by the two types of basket cell show a difference in the subunit composition of GABAA receptors. Terminals of one of the basket cells were identified by antibodies to parvalbumin. Synapses made by parvalbumin‐negative terminals showed five times more immunoreactivity for the α2 subunit than synapses made by parvalbumin‐positive basket cells, whose synapses were frequently immunonegative. This difference is likely to be due to specific GABAA receptor α subunit composition, because neither synaptic size nor immunoreactivity for the β2/3 subunits, indicating total receptor content, was different in these two synapse populations. Synapses established by axo‐axonic cells on axon initial segments showed an intermediate number of immunoparticles for the α2 subunit compared to those made by basket cells but, due to their smaller size, the density of the α2 subunit immunoreactivity was higher in synapses on the axon. Because the two basket cell types innervate the same domain of the pyramidal cell, the results indicate that pyramidal cells have mechanisms to target GABAA receptors, under presynaptic influence, preferentially to distinct synapses. The two basket cell types act via partially distinct GABAA receptor populations.