bluuebunny/crossref_metadata_2025_split huggingface dataset:
DCG‐IV Selectively Attenuates Rapidly Triggered NMDA‐induced Neurotoxicity in Cortical Neurons
Authors: Buisson Alain , Yu Shan Ping , Choi Dennis W. 
Published: April 2006

AbstractMolecular cloning has revealed the existence of at least eight subtypes of metabotropic glutamate receptors (mGluRs). We examined the effect of (2S, 1′R, 2′R, 3′R)‐2‐(2, 3‐dicarboxycyclopropyl)glycine (DCG‐IV), a selective agonist of the mGluR 2/3 subtype, on excitotoxicity in mouse cortical cell cultures. Addition of DCG‐IV to the exposure medium partially attenuated the rapidly triggered excitotoxic death induced by a 5 min exposure to 200 μM NMDA. This neuroprotective effect was reversed by coapplication of α‐methyl‐4‐carboxyphenylglycine (MCPG), an antagonist of mGluRs, by pertussis toxin pretreatment and also by preincubation with dibutyryl cAMP, a stable analogue of cAMP. These results suggest that the activation of mGluR 2/3 is neuroprotective in our system. However, DCG‐IV did not attenuate the slowly triggered neuronal death induced by 24 h exposure to low concentrations of NMDA, α‐amino‐1, 3‐cyclopentanedicarboxylic acid (AMPA) or kainate. The failure of DCG‐IV to block slowly triggered NMDA neurotoxicity is likely due to weak NMDA agonist activity, as demonstrated in whole‐cell recording.
Rab3 Proteins and SNAP‐25, Essential Components of the Exocytosis Machinery in Conventional Synapses, are Absent from Ribbon Synapses of the Mouse Retina
Authors: Grabs D. , Bergmann M. , Urban M. , Post A. , Gratzl M. 
Published: April 2006

AbstractGTP‐binding rab proteins, present in synaptic vesicles and endocrine secretory granules, have been shown to be involved in the control of regulated exocytosis. We found rab3 proteins in immunoblots of diverse areas of the mouse central nervous system (spinal cord, olfactory bulb, hippocampus, cerebellum and neocortex). Immunohistochemical observations at light‐ and electron‐microscopical levels in the hippocampus and other areas revealed rab3 proteins in virtually all synaptic fields and terminals of the areas investigated. In the retina, rab3A immunoreactivity was confined to the inner and outer plexiform layers. Ultrastructural examination revealed that rab3A was present in conventional terminals in the inner plexiform layer and in horizontal cell processes of the outer plexiform layer. In contrast ribbon synapses, which play a key role in transferring information from the photoreceptor cells to the central nervous system, were immunonegative. We also tested whether other proteins of the rab3 family are present in ribbon synapses. However, using an antibody recognizing rab3B and rab3C in addition to rab3A, we found no immunoreactivity in these synapses. Interestingly, we observed also no immunoreactivity for synaptosomal‐associated protein 25 (SNAP‐25) in ribbon synapses, but conventional synapses and horizontal cell processes were heavily stained. Our data show that the known rab3 and SNAP‐25 isoforms, which are components of the secretory apparatus of conventional synapses, are absent from ribbon synapses of the retina. Our observations suggest different mechanisms of transmitter exocytosis in conventional and ribbon terminals.
Potassium Channel mRNA Expression in Prevertebral and Paravertebral Sympathetic Neurons
Authors: Dixon Jane E. , McKinnon David 
Published: April 2006

AbstractThe expression of eighteen different voltage‐activated potassium channel genes in rat sympathetic ganglia was quantitatively analysed using an RNase protection assay. Eleven α‐subunit genes and two β‐subunit genes were expressed in sympathetic ganglia. The relative level of potassium channel mRNA expression was compared between the superior cervical ganglion (SCG) and two prevertebral sympathetic ganglia, the coeliac ganglion (CG) and the superior mesenteric ganglion (SMG). Four mRNAs were differentially expressed: Kv1.2, Kv1.4, Kv2.2 and Kvβ1. Transcripts from all four genes were more abundant in the prevertebral ganglia. From comparisons with previous electrophysiological studies it was concluded that genes encoding the channels underlying the M‐current and D2‐current, which are both prominent in sympathetic neurons, have yet to be identified. It was also concluded that members of the Kv4 family are likely to underlie the low‐threshold A‐current in sympathetic neurons.
Assumptions and Validations of Statistical Tests for Functional Neuroimaging
Authors: Roland P. E. , Gulyas B. 
Published: April 2006

AbstractWe contrast two statistical methods: three‐dimensional cluster analysis and statistical parametric mapping. We show that three‐dimensional cluster analysis is based on a neurobiological theory of the regulation of blood flow and, unlike statistical parametric mapping, carries a minimum of assumptions that are tested. Statistical parametric mapping is a formal approach, which is based on a multitude of assumptions of which the majority have not been validated. We also demonstrate that in practice three‐dimensional cluster analysis has a reasonable balance between sensitivity and the probability of false positives, giving high reproducibility with data on e.g. colour discrimination.
The Reinforcing Properties of Nicotine are Associated with a Specific Patterning of c‐fos Expression in the Rat Brain
Authors: Pagliusi Sonia R. , Tessari Michela , DeVevey Sabine , Chiamulera Christian , Pich Emilio Merlo 
Published: April 2006

AbstractRats were trained for nicotine intravenous infusions in a self‐administration paradigm. The effect of nicotine self‐administration on regional brain activity was studied by mapping changes of c‐fos expression. Specific nicotine effects were determined by comparing the patterning of Fos‐like immunoreactivity (Fos‐LI) in nicotine self‐administering rats with that in three different control groups. Controls included rats exposed to the same manipulation as nicotine self‐administering rats who received intravenous saline instead of nicotine. In addition, two groups of untrained sham‐operated rats exposed daily to the same operant boxes were included: one group had the same food restriction used in the operant training, the other was fed ad libitum. Nicotine self‐administration, exposure to saline and food restriction increased Fos‐LI in 43, 33 and three brain regions, respectively, when compared with the control group fed ad libitum. Computer‐assisted image analysis of Fos‐LI profiles performed on 16 relevant limbic and sensory structures showed that in saline‐treated rats a significant (P < 0.01) increase of Fos‐LI profiles was observed in medial prefrontal cortex, lateral septum, core and ventral shell of nucleus accumbens, claustrum, amygdaloid nuclei, paraventricular thalamic nucleus and lateral geniculate nucleus. A significant (P < 0.01) further increase produced by nicotine was found in medial prefrontal cortex and ventral shell of nucleus accumbens. Interestingly, cingulate and piriform cortex, superior colliculus and medial terminal nucleus of the accessory optic tract were specifically activated by nicotine but not saline. These results show that nicotine self‐administration activates sensory structures, as well as limbic structures involved in natural rewarding pathways. The results suggest the involvement of restricted terminal regions of the mesocorticolimbic dopaminergic system in the maintenance of nicotine self‐administration.
Long‐term Induction of Haem Oxygenase‐1 (HSP‐32) in Astrocytes and Microglia Following Transient Focal Brain Ischaemia in the Rat
Authors: Koistinaho Jari , Miettinen Susanna , Keinänen Riitta , Vartiainen Nina , Roivainen Reina , Laitinen Jarmo T. 
Published: April 2006

AbstractHaem oxygenase‐1 (HO‐1) is a stress protein and a rate‐limiting enzyme in haem degradation, generating ferrous iron, carbon monoxide and bile pigments. HO‐1 has been suggested to be protective against oxidative stress. In the normal rodent brain the enzyme is localized in selected neuron populations, but heat shock, glutathione depletion in vivo and oxidative stress in vitro induce HO‐1 predominantly in glial cells. We studied HO‐1 expression in the brain following transient occlusion of the middle cerebral artery, and found increased mRNA levels in the ischaemic region from 4 h to 7 days after 90 min of ischaemia. The mRNA levels peaked at 12 h, and were localized perifocally. HO‐1‐immunoreactive astrocytes and microglial cells were seen in the perifocal area, in the ipsilateral and occasionally in the contralateral hippocampus. Some perifocal neurons were also HO‐14mmunoreactive. In the infarcted area HO‐1‐positive microglia/macrophages were detected in double‐labelling experiments. A microassay measuring the conversion of [14C]haem to [14C]bilirubin showed a two‐fold increase in haem oxygenase activity in the infarcted core. These observations show a long‐term induction of HO‐1 protein and its activity following ischaemia‐reperfusion brain injury, and indicate increased capacity for haem degradation and the generation of biologically active bile products, carbon monoxide and iron in astrocytes and some microglia/macrophages during focal brain ischaemia.
Distribution of GABAergic Elements Postsynaptic to Ventroposteromedial Thalamic Projections in Layer IV of Rat Barrel Cortex
Authors: Staiger Jochen F. , Zilles Karl , Freund Tamás F. 
Published: April 2006

AbstractThe spatial synaptic pattern formed by boutons, originating in the ventroposteromedial thalamic nucleus, with GABAergic neurons in the rat barrel cortex was mapped. The aim was to shed light on the structural basis by which inhibitory circuits may be activated at the first stage of cortical information processing. The thalamic afferent projection was labelled by anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA‐L), whereas the GABAergic targets in layer IV of the rat barrel cortex were visualized by postembedding GABA immunogold‐labelling or by pre‐embedding parvalbumin immunocytochemistry. In the first set of experiments, we mapped barrels, contained in single ultrathin sections, by means of a computer‐controlled electron microscope stage in their entire layer IV representation. From a total of 1199 asymmetric PHA‐L‐labelled synapses, only 98 were on GABAergic elements, mainly on dendritic shafts. This corresponded to 8.2% of all synapses counted. These synapses on GABAergic targets were essentially homogeneously distributed without a reliable relationship to barrel subdivisions, i.e. hollow versus wall; or layer IVa versus layer IVb. In the second part of the study, we demonstrated that parvalbumin‐containing neurons represent the major GABAergic cell type targetted by thalamic afferents in layer IV of the barrel cortex, since all parvalbumin‐positive cells investigated received multiple synaptic contacts (up to eight synapses per neuron) from the ventroposteromedial thalamic nucleus. These results imply that interneurons responsible for perisomatic inhibition (basket and chandelier cells known to contain parvalbumin) are likely to be strongly excited by thalamic afferents, despite the relatively low proportion of thalamic synapses on GABAergic elements compared to spines of principal cells, and participate in the early stages of cortical sensory information processing.
Neuronal Precursors in the Postnatal Mouse Cerebellum are Fully Committed Cells: Evidence from Heterochronic Transplantations
Authors: Jankovski Aleksandar , Rossi Ferdinando , Sotelo Constantino 
Published: April 2006

AbstractNeural progenitors are thought to be multipotent cells whose adult phenotype is determined by extrinsic influences acting during and immediately after their last mitosis. To test this hypothesis, postnatal cerebellar precursor cells were placed in the heterochronic cellular environment of the embryonic mouse cerebellar anlage and the resulting phenotypes were determined. To identify the cells arising from postnatal precursors, tissue fragments taken from 3‐ to 8–day‐old cerebellum of several transgenic mouse lines (each expressing the lacZ reporter gene in different sets of neuronal populations) were mixed with fragments taken from the wild‐type cerebellar primordium of 12‐ or 13–day‐old embryos. The fragments were dissociated and grafted into the cerebellum of adult mice. The phenotype acquired by postnatal precursors in the mixed grafts was determined by their morphology and ultrastructural features and by the expression of specific markers. Only two adult phenotypes were generated by these precursors: granule cells and molecular layer interneurons. Most granule cells were well integrated in the trilaminated cortex of the graft, being positioned in their proper layer both during development and after complete maturation. By contrast, basket and stellate cells were always ectopic, remaining outside the molecular layer. These results indicate that at least two distinct progenitor cells are present in the postnatal cerebellar cortex under the experimental conditions of this study. Both progenitors appear to be strictly specified at the time of grafting, and neither their identity nor the expression of their major distinctive features are significantly influenced by local signals emerging from the cellular environment of the embryonic cerebellar anlage.
Induction of Dopaminergic Neurotransmitter Phenotype in Rat Embryonic ‐Cerebrocortex by the Synergistic Action of Neurotrophins and Dopamine
Authors: Zhou Jiawei , Bradford Henry F. , Stern Gerald M. 
Published: April 2006

AbstractNeurotrophins, including nerve growth factor, brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3) and neurotrophin‐4/51 (NT‐4/5), have been shown to enhance survival and differentiation of a variety of central neuronal populations, such as those with the dopaminergic, cholinergic, GABAergic phenotype during development. In this paper we present evidence that BDNF, NT‐3 and NT‐4/5 acting synergistically with dopamine (DA) can artificially induce the full dopaminergic phenotype in rat fetal cerebral cortex which normally has very few dopaminergic neurons in adulthood. Thus, BDNF/DA, NT‐3/DA, NT‐4/DA elicited a great increase in the number of tyrosine hydroxylase (TH)‐immunoreactive cells, which was up to 57% of total neuronal population in cultures of fetal rat cortical cells. This stimulatory effect was not dependent on glial proliferation, or on addition of serum to the culture. Pharmacological studies showed that dopamine receptors D, and D2 were involved in this effect. The TH’cortical cells possessed other biochemical phenotypic features of dopaminergic neurons. Thus, high‐affinity DA uptake was elevated in cortical cultures treated with neurotrophin/DA. Also DA and 3,4–dihydroxyphenlacetic acid production was detected (5.42 ± 1.24 and 13.72 ? 2.84 pmol/dish respectively, zero in controls). This shows the presence of functionally active TH, aromatic acid decarboxylase and monoamine oxidase. Neurotrophins/DA had no effect on noradrenergic phenotype expression by cortical fetal cells. Taken together, these results support the long‐standing view that development of the central nervous system is determined not only by intrinsic genetic programmes, but also involves environmental influences such as the action of growth factors and extracellular neurotransmitters. In this case we report the effect of specific DA phenotype‐inducing agents.
5‐HT1A Receptor Agonist Flesinoxan Enhances Fos Immunoreactivity in Rat Central Amygdala, Bed Nucleus of the Stria Terminalis and Hypothalamus
Authors: Compaan J. C. , Groenink L. , van der Gugten J. , Maes R. A. A. , Olivier B. 
Published: April 2006

Abstract5‐Hydroxytryptamine‐1A (5‐HT1A) receptor agonists, including flesinoxan, reduce anxiety and activate the hypothalamus‐pituitary‐adrenal (HPA) axis under basal conditions. In order to investigate the underlying neural mechanisms we investigated immunoreactivity for the immediate early gene protein product Fos (Fos‐ir) in rat brains 1 h after flesinoxan treatment (0.0, 0.3 or 3.0 mg/kg p.0.). Typically, 5‐HT1A receptor‐containing brain areas, such as the dorsal raphe nuclei, hippocampus, septum, diagonal band and the cortical and basomedial amygdala, do not show Fos‐ir. Apparently, binding of flesinoxan at the 5‐HT1A receptor does not directly lead to activation of c‐fos in the cell, probably due to its negative coupling to adenylate cyclase. However, in typically non‐5HTlA receptor‐containing brain areas Fos‐ir is increased due to flesinoxan treatment, as in the paraventricular nucleus of the hypothalamus (PVN), the dorsolateral part of the bed nucleus of the stria terminalis (BNSTd1) and the central amygdala (CeA). Flesinoxan‐treated rats also exhibited higher plasma corticosterone levels than vehicle‐treated animals, which suggests the involvement of corticotropin‐releasing hormone (CRH) or vasopressin in the hypothalamus. After double immunolabelling (Fos/CRH or Fos/vasopressin), every CRH neuron detected in the PVN also contained Fos. Moreover, a significant correlation existed between the number of Fos‐ir neurons in the PVN and the plasma corticosterone level. Hardly any Fos/ vasopressin double labelling was visible in the PVN. Accordingly, flesinoxan exerts its activating effects on the HPA axis via CRH neurons in the PVN. These effects are transsynaptically mediated by other brain areas, such as the CeA and BNSTdl, which also show increased Fos‐ir.
Role of Thyroid Hormone in the Morphological Differentiation and Maturation of Astrocytes: Temporal Correlation with Synthesis and Organization of Actin
Authors: Paul Surojit , Das Sumantra , Poddar Ranjana , Sarkar Pranab Kumar 
Published: April 2006

AbstractMorphological changes and the molecular mechanisms associated with the maturation of astrocytes were studied under normal and thyroid hormone‐deficient conditions using long‐term (30 days) primary cultures derived from the neonatal rat brain. Immunocytochemical staining of cells with a monoclonal antibody specific to glial fibrillary acidic protein demonstrated for the first time that, similar to their maturation in vivo, astrocytes maintained in normal serum‐containing medium can undergo complete maturation involving two distinct stages of morphological differentiation (from radial glia to flat polygonal cells with epithelioid morphology and then to mature process‐bearing cells with stellate morphology). Deficiency of thyroid hormone delays the first step and totally blocks the second stage of differentiation in the maturation process. Comparative staining of normal and thyroid hormone‐deficient astrocytes with filamentous actin‐specific fluorescein isothiocyanate‐phalloidin and quantitation of the various forms of intracellular actin using an improved DNase I assay demonstrated that maturation of astroglial cells is associated with characteristic alterations in the level of cytoskeletal and non‐cytoskeletal filamentous (F) actin. In particular, the maintenance of the epithelioid form of the hypothyroid astrocytes is associated with a progressive increase in the level of cytoskeletal F‐actin and a concomitant decline in the level of non‐cytoskeletal F‐actin. Quantitation of actin mRNA by Northern blot analysis and studies on the rate of actin synthesis at various stages of differentiation showed that the initial transformation into the epithelioid form is associated with an increase in the rate of synthesis of actin and the expression of its mRNA, while the final transformation into the mature process‐bearing form is correlated with a decline in these parameters. The results indicate that thyroid hormone plays an obligatory role in promoting the differentiation and maturation of astrocytes, and that during this process the hormone regulates the expression of actin and its intracellular organization in a way conducive to morphological differentiation.
The Calretinin‐containing Mossy Cells Survive Excitotoxic Insult in the Gerbil Dentate Gyrus. Comparison of Excitotoxicity‐induced Neuropathological Changes in the Gerbil and Rat
Authors: Kotti T. , Tapiola T. , Riekkinen P. J. , Miettinen R. 
Published: April 2006

AbstractOur preliminary results showed that mossy fibres do not undergo sprouting after global ischaemia in gerbils, although the pattern of hippocampal cell damage resembled that seen in ischaemic and epileptic rats, where mossy fibre sprouting is known to occur. In order to investigate whether the observed differences in the appearance of mossy fibre sprouting are related to the animal model or species used, this study was undertaken to compare the neuropathological changes induced in gerbils by systemic injection of kainate or by occlusion of carotid arteries with the changes induced in rats by injection of kainate. The pattern of pyramidal cell damage was very similar in each group. Mossy fibre sprouting was present in epileptic rats but not in ischaemic or epileptic gerbils. The number of somatostatin‐immunoreactive neurons was decreased in the hilus of epileptic rats and ischaemic gerbils, but not in epileptic gerbils. The analysis of calretinin immunoreactivity in the dentate gyrus revealed differences between the rat and gerbil. The most striking difference between these species was that the mossy cells contained calretinin in gerbils but not in rats. Cell counting showed that the calretinin‐containing mossy cells had survived both in epileptic and ischaemic gerbils. Therefore, since the mossy cells are known to be highly susceptible to excitotoxic insult in rats and degeneration of these cells is thought to be a key element in the induction of mossy fibre sprouting, we propose that the absence of mossy fibre sprouting in gerbils is related to the survival of the mossy cells.
Expression of Kainate‐selective Glutamate Receptor Subunits in Glial Cells of the Adult Bovine White Matter
Authors: Garcia‐Barcina Jose M. , Matute Carlos 
Published: April 2006

AbstractIt is now well established that glial cells, like neurons, express a large variety of non‐NMDA glutamate receptors. However, knowledge about the subunits forming the receptors and the types of glial cells which express them is incomplete. The aim of this study was to determine the presence and distribution of kainate‐preferring glutamate receptor subunits in glial cells in the white matter of adult cattle. To this end, reverse transcription and polymerase chain reaction (RT‐PCR) analysis of mRNA extracted from the corpus callosum, fornix and optic nerve of brains of adult cattle was carried out using specific primers that allowed selective amplification of the kainate transcripts encoding the GluR5, GluR6, GIuR7, KAI and KA2 subunits. In the three areas studied, transcripts for all five subunits were detected. Restriction digestion of the amplified products confirmed the specificity of the PCR amplifications and showed that the extent of Q/R editing in the GluR6 subunit was lower than that described in the rat whole brain. Immunohistochemical experiments revealed that GluR5‐7 and KA2 subunits appeared in ‐50% of astrocytes and 40% of oligodendrocytes. In astrocytes the receptor subunits were located throughout the cell body and processes, whereas in oligodendrocytes they were mostly restricted to the soma. Double‐labelling studies demonstrated that in the white matter areas studied GluR5‐7 and KA2 subunits are coexpressed in the majority of macroglial cells endowed with kainate receptors. In addition, astrocytes, but not oligodendrocytes, expressing kainate‐selective receptors were found to possess the GluR1 subunit, an γ‐amino‐3‐hydroxyd‐methyl‐4‐isoxazole propionic acid (AMPA) receptor subunit which has previously been found in this macroglial cell type. Taken together, these results provide evidence for the presence and molecular diversity of kainate‐selective receptor subunits in glial cells of the adult white matter and for their co‐expression with AMPA receptor subunits. The widespread distribution of kainate receptors in glial cells of the white matter suggests that these receptors may be important in axon‐to‐glia and/or glia‐to‐glia signalling.