bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversal of glutamate excitotoxicity by activation of PKC‐associated metabotropic glutamate receptors in cerebellar granule cells relies on NR2C subunit expression
Authors: Pizzi Marina , Boroni Flora , Bianchetti Konstantinos Moraitis andrea , Memo Maurizio , Spano PierFranco 
Published: March 2003

AbstractStimulation of metabotropic glutamate receptors (mGluRs) belonging to group I has been found to reduce N‐methyl‐ d‐aspartate (NMDA) receptor function in terms of both intracellular calcium concentration ([Ca2+]i) rise and neurotoxicity in cultured cerebellar granule cells. In the present study, we investigated whether the mGluR‐elicited modulation of glutamate responses might rely on the heteromeric composition of NMDA receptor channel. NMDA receptors consist of two distinct groups of subunits: NR1, that is ubiquitously in the receptor complexes; and NR2A–D, that differentiate and potentiate NMDA receptor responses by assembling with NR1. Among NR2 subunits, only NR2A and NR2C mRNAs and relative proteins are detected in cerebellar granule cells at 10 days in vitro. To dissect the involvement of the two different subunits in making the NMDA receptor channel sensitive to modulation by group I mGluR agonists, expression of the NR2C subunit was prevented by treating the cells with specific antisense oligodeoxynucleotide (ODN). The capability of the mGluR agonists, trans‐1‐amino‐cyclopentane‐1,3‐dicarboxylic acid (tACPD, 100 μm) or 3 hydroxyphenylglycine (3HPG, 100 μm), and the protein kinase C (PKC) activator, 4β‐phorbol‐12,13‐dibutyrate (PDBu, 1 μm), to inhibit the function of resultant NMDA receptors was then evaluated. We found that depletion of the NR2C subunit abolished the inhibitory effect of group I mGluR stimulation on glutamate‐induced [Ca2+]i rise and neurotoxicity. The antisense ODN treatment also prevented the inhibitory effect of PDBu on glutamate responses. Conversely, in NR2C‐lacking neurons, both group I mGluRs and PKC stimulation enhanced NMDA receptor‐mediated effects. The present findings indicate that the capability of PKC‐associated mGluRs to modulate native NMDA receptor function relies on the heteromeric configuration of the receptor–channel complex. Particularly, expression of the NR2C subunit is required to make the NMDA receptor sensitive to inhibitory modulation by mGluRs or PKC activation.
Tenascin‐R interferes with integrin‐dependent oligodendrocyte precursor cell adhesion by a ganglioside‐mediated signalling mechanism
Authors: Probstmeier Rainer , Michels Marion , Franz Thomas , Chan Bosco M. C. , Pesheva Penka 
Published: March 2003

AbstractOligodendrocyte (OL) lineage progression is characterized by the transient expression of the disialoganglioside GD3 by OL precursor (preOL) cells followed by the sequential expression of myelin‐specific lipids and proteins. Whereas GD3+ preOLs are highly motile cells, the migratory capacity of OLs committed to terminal differentiation is strongly reduced, and we have recently shown that the extracellular matrix protein tenascin‐R (TN‐R) promotes the stable adhesion and differentiation of O4+ OLs by a sulphatide‐mediated autocrine mechanism (O4 is a monoclonal antibody recognizing sulphatides/seminolipids expressed by OLs and in myelin). Using culture conditions that allow the isolation of mouse OLs at distinct lineage stages, here we demonstrate that TN‐R is antiadhesive for GD3+ preOLs and inhibits their integrin‐dependent adhesion to fibronectin (FN) by a disialoganglioside‐mediated signalling mechanism affecting the tyrosine phosphorylation of the focal adhesion kinase. This responsive mechanism appears to be common to various cell types expressing disialogangliosides as: (i) disialogangliosides interfered with the inhibition of cell adhesion of different neural and non‐neural cells on substrata containing TN‐R and FN or RGD‐containing FN fragments. TN‐R interacted specifically with disialoganglioside‐expressing cells or immobilized gangliosides, and ganglioside treatment of TN‐R substrata resulted in a delayed preOL cell detachment as a function of time. We conclude that OL response to one and the same signal in the extracellular matrix critically depends on the molecular repertoire expressed by OLs at different lineage stages and could thus define their final positioning.
The effect of Etomidate on sensory transmission in the dorsal column pathway in the urethane‐anaesthetized rat
Authors: Angel A. , Arnott R. H. 
Published: March 2003

AbstractThe effect of Etomidate, a general anaesthetic, on sensory afferent transmission was measured in the dorsal column pathway in urethane‐anaesthetized rats. Extracellular recordings were made of peripherally evoked responses by single cells in the cuneate nucleus, ventroposterolateral nucleus of the thalamus and laminae IV–VI of the primary somatosensory cortex. Cortical mass responses were also recorded. In further experiments, cortical mass responses were evoked antidromically by stimulation in the pyramidal tract. The effect of incremental administration of Etomidate on evoked responses was recorded. These results are compared with the previously reported effects of urethane, a ‘conventional’ anaesthetic. Etomidate did not alter cuneate or ventroposterolateral thalamic cell responses but it caused a dose‐dependent reduction in cortical cell responsiveness. It failed to alter antidromically evoked cortical mass responses. Etomidate differs from the majority of anaesthetics, which act in the thalamus, and appears to cause perturbation at the cortical level.
Architecture and connections of retrosplenial area 30 in the rhesus monkey (macaca mulatta).
Authors: Morris Renée , Petrides Michael , Pandya Deepak N. 
Published: March 2003

AbstractBecause of the sharp curvature of the retrosplenial region around the splenium of the corpus callosum, standard coronal sections are not appropriate for architectonic analysis of its posteroventral part. In the present study, examination of the posteroventral retrosplenial region of the rhesus monkey in sections that were orthogonal to its axis of curvature (and therefore appropriate for architectonic analysis) has permitted definition of its architecture and precise extent. This analysis demonstrated that areas 29 and 30 of the retrosplenial cortex, as well as adjacent area 23 of the posterior cingulate cortex, extend together as an arch around the splenium of the corpus callosum and maintain their topographical relationship with one another throughout their entire course. Injections of anterograde and retrograde tracers confined to retrosplenial area 30 revealed that this area has reciprocal connections with adjacent areas 23, 19 and PGm, with the mid‐dorsolateral part of the prefrontal cortex (areas 9, 9/46 and 46), with multimodal area TPO in the superior temporal sulcus, as well as the posterior parahippocampal cortex, the presubiculum and the entorhinal cortex. There are also bidirectional connections with the lateroposterior thalamic nucleus, as well as the laterodorsal and the anteroventral limbic thalamic nuclei. The connectivity of area 30 suggests that it may play a role in working memory processes subserved by the mid‐dorsolateral frontal cortex in interaction with the hippocampal system.
Acute reorganization of the forepaw representation in the rat SI cortex after focal cortical injury: neuroprotective effects of piracetam treatment
Authors: Coq Jacques‐Olivier , Xerri Christian 
Published: March 2003

AbstractImmediate postlesion reorganization of the somatosensory cortical representation was examined in adult rats. Response properties of small clusters of neurons were recorded in the area of the primary somatosensory cortex (SI) devoted to the contralateral forepaw representation. Electrophysiological maps were elaborated on the basis of the sensory ‘submodality’ (cutaneous or noncutaneous) and the location of the peripheral receptive fields (RFs) of layer IV neurons. Recordings were made prior to, and from 1 to 12 h after, induction of a focal neurovascular lesion to the SI cortex that initially destroyed a part (8.5%) of the cutaneous representation. Moreover, the influence of an anti‐ischaemic substance (piracetam) on lesion‐induced changes was analysed. The main observations were: (i) a gradual outward expansion of the area of the functional lesion, which was smaller in the piracetam‐treated (PT) rats than in the control, placebo‐treated (PL) rats; (ii) a substantial remodelling of the spared representational zones, both in cortical sectors adjoining the site of injury and those remote from the site; (iii) a significant postlesion increase in the size of cutaneous RFs in the PT rats, but not in the PL rats; (iv) a better preservation of RF submodality and topographic organization in the PT maps than in the PL maps; and (v) a decrease in neuronal responsiveness to cutaneous stimulation which was less pronounced in the PT than in the PL rats. Our results can be ascribed to a rapid change in the balance of excitatory and inhibitory connections which leads to unmasking of subthreshold inputs converging onto cortical neurons. Our findings also indicate that acute piracetam treatment exerts a protective function on the physiological response properties of cortical neurons after focal injury.
Allatostatin modulates skeletal muscle performance in crustaceans through pre‐ and postsynaptic effects
Authors: Kreissl Sabine , Weiss Torsten , Djokaj Stefan , Balezina Olga , Rathmayer Werner 
Published: March 2003

AbstractAllatostatins, originally identified in insects as peptide inhibitors of juvenile hormone biosynthesis, are regarded as potent inhibitory regulators of intestinal muscles in insects and crustaceans. However, accumulating data indicate that allatostatins might also be involved in modulation of skeletal neuromuscular events. We show that most ganglia of two isopod crustaceans (Idotea baltica and I. emarginata) contain pairs of large, allatostatin‐immunoreactive motor neurons which supply several segmental muscles. Among them are the dorsal extensor muscles, of which some fibres receive immunoreactive, varicose innervation. We demonstrate, on identified muscle fibres, that allatostatin exerts a twofold inhibitory effect: it reduces contractions of single voltage‐clamped fibres, and it decreases the amplitude of evoked excitatory junctional currents recorded from individual release boutons. No change in excitation‐contraction threshold or in passive membrane parameters was observed. As the amplitude of miniature currents generated by spontaneously released single transmitter quanta was not changed, the inhibitory effect of the peptide on junctional currents must be of presynaptic origin. Supportive results were obtained on leg muscles of the crab Eriphia spinifrons, where allatostatin decreased evoked synaptic currents by reducing the mean number of transmitter quanta released by presynaptic depolarization without affecting the amplitudes of currents generated by single quanta. This effect of allatostatin was similar for two functionally different neurons, the slow and the fast closer excitor.The data show that allatostatin occurs in identified motor neurons of Idotea and exerts complementary pre‐ and postsynaptic modulatory effects which reduce muscle responses. Thus, allatostatin counteracts the effects of another neuropeptide, proctolin, which is also present in Idotea and causes potentiating effects on the same muscle fibres.
Immunological evidence that the β isoform of Ca2+/calmodulin‐dependent protein kinase IV is a cerebellar granule cell‐specific product of the CaM kinase IV gene
Authors: Sakagami Hiroyuki , Umemiya Masashi , Kobayashi Takeshi , Saito Sachiko , Kondo Hisatake 
Published: March 2003

AbstractCa2+/calmodulin‐dependent protein kinase IV (CaM kinase IV) exists as two monomeric isoforms, α and β. In this study, we raised an antibody against the β isoform and provided immunohistochemical evidence for specific expression of the β isoform in cerebellar granule cells as a single gene‐derived translational product distinct from the α isoform. Immunohistochemical examination showed that the β‐immunoreactivity was confined to the nuclei of the cerebellar granule cells, in contrast to the more widespread immunoreactivity for the α isoform in both nuclei and cytoplasm of the cerebellar granule cells and many other neurons with dominant nuclear localization. In developing cerebella, the β‐immunoreactivity gradually appeared in the internal granule cells during the postnatal 2nd and 3rd weeks, while the α‐immunoreactivity had already appeared in the internal granule cells in the 1st postnatal week. Unlike the α isoform, β‐immunoreactivity was not detected in the Purkinje cells at any developmental stages. The differential expression of the α and β isoforms suggests that each isoform may be involved in different cerebellar functions.
Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer’s disease: histotopographical correlation with amyloid plaques and hyperphosphorylated‐tau protein
Authors: Wevers A. , Monteggia L. , Nowacki S. , Bloch W. , Schütz U. , Lindstrom J. , Pereira E. F. R. , Eisenberg H. , Giacobini E. , De Vos R. A. I. , Steur E. N. H. Jansen , Maelicke A. , Albuquerque E. X. , Schröder H. 
Published: March 2003

Abstract
Impairment of cholinergic transmission and decreased numbers of nicotinic binding sites are well‐known features accompanying the cognitive dysfunction seen in Alzheimer’s disease (AD). In order to elucidate the underlying cause of this cholinoceptive dysfunction, the expression of two pharmacologically different nicotinic acetylcholine receptor (nAChR) subunits (α4, α7) was studied in the cerebral cortex of Alzheimer patients as compared to controls. Patch‐clamp recordings of 14 dissociated neurons of control cortices showed responses suggesting the existence of α4‐ and α7‐containing functional nAChRs in the human cortex. In cortices of Alzheimer patients and controls, the pattern of distribution and the number of α4 and α7 mRNA‐expressing neurons were similar, whereas at the protein level a decrease in the density of α4‐ and α7‐expressing neurons of ≈ 30% was observed in Alzheimer patients. The histotopographical correlation of nAChR expression with accompanying pathological changes, e.g. accumulation of hyperphosphorylated‐tau (HP‐tau) protein and β‐amyloid showed that neurons in the vicinity of β‐amyloid plaques bore both nAChR transcripts. Neurons heavily labelled for HP‐tau, however, expressed little or no α4 and α7 mRNA. These results point to an impaired synthesis of nAChRs on the protein level as a possible cause of the cholinoceptive deficit in AD. Further investigations need to elucidate whether interactions of HP‐tau with nAChR mRNA, or alterations in the quality of α4 and α7 transcripts give rise to decreased protein expression at the level of individual neurons.
Post‐translational modifications of ICA512, a receptor tyrosine phosphatase‐like protein of secretory granules
Authors: Hermel Jean‐Michel , Dirkx Ronald , Solimena Michele 
Published: March 2003

AbstractThe autoantigen of type I diabetes ICA512 is a receptor tyrosine phosphatase‐like protein enriched in the secretory granule membranes of neurons and peptide secreting endocrine cells. While the function of ICA512 remains unknown, it is thought to link regulated neuropeptide and peptide hormone secretion with signal transduction pathways involving tyrosine phosphorylation/dephosphorylation. To characterize further its biochemical properties, we conducted studies in the bovine pituitary, an abundant source of native ICA512, as well as in fibroblasts transfected with various human ICA512 cDNA constructs. Based on these studies we have established that the signal peptide of ICA512 encompasses residues 1–34 and that the ectodomain of ICA512 undergoes multiple post‐translation modifications, including N‐glycosylation. Newly synthesized ICA512 appears first as a pro‐protein of 110 kDa that is then converted by post‐translational modifications into a 130‐kDa species. Cleavage of pro‐ICA512 at a consensus for furin‐like convertases generates a 60–66‐kDa ICA512 transmembrane fragment (amino acids 449–979). Such processing ICA512 is not restricted to neuroendocrine cells, as it can also occur in transfected fibroblasts. Finally, the predicted N‐terminal fragment of ICA512 resulting from this cleavage (amino acids 35–448) or parts thereof are present in the neurosecretosomes of posterior pituitary, raising the possibility that they may be secreted upon exocytosis of secretory granules.
Cerebellar Golgi cells in the rat: receptive fields and timing of responses to facial stimulation
Authors: Vos Bart P. , Volny‐Luraghi Antonia , De Schutter Erik 
Published: March 2003

AbstractGolgi cells are the only elements within the cerebellar cortex that inhibit granule cells. Despite their unique position there is little information on how Golgi cells respond to afferent input. We studied responses of Golgi cells to mechanical stimulation of the face, in Crus I‐II of ketamine‐xylazine anaesthetized rats. In 41 rats, 87 putative Golgi cells were identified, based on spike characteristics and on location of electrolytic lesions in the granular layer. They displayed a slow firing rhythm at rest (8.4 spikes/s). Most Golgi cells (84%) showed excitatory responses to tactile input. Their receptive fields (RFs) included, in 78%, the entire ipsilateral infraorbital nerve territory, and extended, in 14%, to other trigeminal nerve branches and, in 48%, to the contralateral face. Excitatory responses consisted of multiple, precisely timed (± 1 ms) spikes. Most peristimulus time histograms (PSTHs) (69%) showed an early (5–10 ms) and a late (13–26 ms) excitatory component, with each component consisting of a single PSTH peak. In some PSTHs the early component was a double peak (< 4 ms interval). In others, only one, early or late, PSTH peak was observed. The excitatory components were followed by a silent period (28–69 ms latency), the duration of which (13–200 ms) varied with response amplitude. In single cells, response profiles changed with stimulus location. In simultaneously recorded cells, evoked profiles differed for identical stimuli. Differences in RF size between early ‘double’ and ‘single’ peaks suggested that they resulted from direct mossy fibre and parallel fibre input, respectively. Late PSTH peaks were assumed to reflect corticopontine activation.
Astrocytes regulate the developmental appearance of GABAergic and glutamatergic postsynaptic currents in cultured embryonic rat spinal neurons
Authors: Li Yong‐Xin , Schaffner Anne E. , Barker Jeffery L. 
Published: March 2003

AbstractThe effects of astrocytes on the emergence of synaptic transients and excitable membrane properties in cultured, embryonic, rat ventral spinal neurons were studied with electrical and optical recording techniques. Neurons on astrocytes had significantly longer neurites and an accelerated rate of growth in surface membrane during the initial 24 h in culture compared to neurons on poly‐ d‐lysine (PDL). GABAergic (GABA, γ‐aminobutyric acid) and glutamatergic transients appeared spontaneously in co‐cultured neurons by 24 h. GABAergic quanta did not appear in neurons on PDL until 4 days in culture, and glutamatergic transients did not emerge until 7 days in culture. Astrocyte‐conditioned medium (ACM) partially mimicked the effects of direct astrocytic contact. GABAergic transients appeared by 2 days, and glutamatergic signals by 4 days in neurons on PDL exposed to ACM. All of the spontaneous, synaptic‐like transients were eliminated by tetrodotoxin or Ca2+o‐free saline, implicating voltage‐dependent cation channels in their generation. Astrocytes immediately and significantly increased the density of voltage‐dependent Na+ currents compared to neurons on PDL, but by the end of 24 h, Na+ current densities were identical. Electrophysiological and optical recording revealed comparable densities of high‐voltage‐activated (HVA) Ca2+ currents on both co‐cultured neurons and neurons on PDL throughout the first week. However, neurons on astrocytes had significantly greater contributions of P/Q‐type currents and lesser contributions of L‐type currents beginning at 24 h and continuing for 7 days. The contribution of N‐type current was significantly more in co‐cultured neurons only at 24 h. Thus, in vitro, astrocytes help to differentiate specific excitable membrane properties in spinal neurons, along with GABAergic and glutamatergic forms of synaptic transmission.
Opioids modulate cell division in the germinal zone of the late embryonic neocortex
Authors: Reznikov Kyrill , Hauser Kurt F. , Nazarevskaja Galina , Trunova Yulia , Derjabin Vasily , Bakalkin Georgy 
Published: March 2003

AbstractOpioid effects on cell division in the embryonic cerebral cortex were examined using two experimental approaches: (i) the presence of opioid receptors in the embryonic day 16 mouse neocortex was tested using immunohistochemical techniques; (ii) the values of the indices of [3H]thymidine pulse labelled cells and mitotic indices were estimated in the ventricular zone of the embryonic day 16 mouse neocortex 2.5, 4.5 and 8.5 h after administration to pregnant females of selected opioid receptor agonists or the opioid antagonist naloxone. The immunohistochemical study demonstrated that distinct subpopulations of the ventricular zone cells express μ, δ or κ opioid receptors. Acute exposure of mouse embryos to μ, δ and κ opioid receptor agonists or naloxone differentially affects the indices of [3H] thymidine pulse labelled cells and mitotic indices indicating changes in the cell cycle composition. Treatment with the μ opioid receptor agonist D‐Ala2‐MePhe4, Gly‐ol5‐enkephalin (DAGO), or the partially selective κ opioid receptor agonist bremazocine, increased the [3H]thymidine labelling and mitotic indices. In contrast, the δ receptor agonist (D‐Ser8)‐leucine enkephalin‐Thr (DSLET) produced a decrease in the labelled cell indices and mitotic indices. Naloxone provided a biphasic effect: a decrease in the values of labelled cell indices 2.5 h after naloxone administration, followed by an increase in the values of the indices at 4.5 and 8.5 h. These results suggest that the endogenous embryonic/maternal opioid systems are involved in the regulation of cell division in the ventricular zone of the late embryonic cortex.
Visual‐field‐specific heterogeneity within the tecto‐rotundal projection of the pigeon
Authors: Hellmann Burkhard , Güntürkün Onur 
Published: March 2003

AbstractThe organization of the tecto‐rotundal projection of the pigeon was investigated by means of anterograde and retrograde tracing techniques. Besides the known organization in tecto‐rotundal connectivity, this study additionally demonstrates major variations in the ascending projections of different tectal subfields. We show that the ventral tectum opticum (TO) has significantly more projections onto the nucleus rotundus (Rt) than dorsal tectal areas. This difference coincides with differential innervation densities of afferent fibres within rotundal subregions. While ventral tectal efferents project onto the ventral and central Rt, dorsal tectal efferents mainly arborize within limited areas between the central Rt and its dorsal cap, the nucleus triangularis. Thus, the ventral TO, representing the lower and frontal field of view, exhibits a quantitatively and spatially enhanced projection onto the Rt, as compared with the dorsal TO. The data presented here demonstrate a visual field‐dependent projection pattern of ascending tectal outputs onto different rotundal domains. The data are consistent with behavioural studies, demonstrating tectofugal lesions to suppress visual stimulus analysis mainly within the frontal field of view.