bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity and regulation of cellular prion protein glycoforms in neuronal cell lines
Authors: Monnet Céline , Marthiens Véronique , Enslen Hervé , Frobert Yveline , Sobel André , Mège René Marc 
Published: August 2003

AbstractThe normal cellular prion protein is a small sialoglycoprotein highly expressed in neurons, the physiological function of which is largely unknown. Due to extensive N‐glycosylations with a wide range of oligosaccharides, the prion protein displays a complex glycosylation pattern that could be of relevance for its function. The cellular prion protein patterns in adult mouse and rat brain, and in neuronal cell lines, appeared highly heterogeneous, as distinct levels and glycoforms of cellular prion protein were revealed by immunoblotting of corresponding samples. Amongst neuronal cell lines, mouse N2a neuroblastoma cells expressed low levels of endogenous prion protein. Mouse hypothalamic GT1‐7 cells and rat pheochromocytoma PC‐12 cells expressed highly glycosylated forms of cellular prion protein that were found neither in adult mouse and rat brain, nor in mouse brain during development. In contrast, rat B104 neuroblastoma cells abundantly expressed N‐glycosylated cellular prion protein forms similar to those observed in mouse and rat brain. In all these cell lines, the prion protein was normally exported to and expressed at the outer cell membrane. Our results suggest that B104 cells may represent an appropriate cell model to investigate the physiological role of cellular prion protein in further detail as they highly express the normal ‘brain‐like’ cellular prion protein glycoforms. In addition, we observed that the various prion glycoforms in B104 cells were tightly regulated both as a function of cell density and during neuronal differentiation, implying a potential role of cellular prion protein in cell–cell interactions and differentiation.
Involvement of platelet‐activating factor and LIS1 in neuronal migration
Authors: Tokuoka Suzumi M. , Ishii Satoshi , Kawamura Noriko , Satoh Mamoru , Shimada Atsuyoshi , Sasaki Shinji , Hirotsune Shinji , Wynshaw‐Boris Anthony , Shimizu Takao 
Published: August 2003

AbstractPlatelet‐activating factor (PAF, 1‐O‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine) is a biologically active lipid mediator. We have previously shown the expression of PAF receptor in neurons and microglia. PAF is produced in the brain from its precursor, and degraded by the enzyme PAF acetylhydrolase. LIS1 is a regulatory subunit of PAF acetylhydrolase, and is identical to a gene whose deletion causes the human neuronal migration disorder, type I lissencephaly. Indeed, Lis1 mutant mice display defects in neuronal migration and layering in vivo, and also in cerebellar granule cell migration in vitro. However, the roles of PAF and the PAF receptor in the neuronal migration remain to be determined. Here, we show that PAF receptor‐deficient mice exhibited histological abnormalities in the embryonic cerebellum. PAF receptor‐deficient cerebellar granule neurons migrated more slowly in vitro than wild‐type neurons, consistent with the observation that a PAF receptor antagonist reduced the migration of wild‐type neurons in vitro. Synergistic reduction of neuronal migration was observed in a double mutant of PAF receptor and LIS1. Unexpectedly, PAF affected the migration of PAF receptor‐deficient neurons, suggesting a receptor‐independent pathway for PAF action. The PAF receptor‐independent response to PAF was abolished in granule neurons derived from the double mutant mice. Thus, our results suggest that the migration of cerebellar granule cells is regulated by PAF through receptor‐dependent and receptor‐independent pathways, and that LIS1 is a pivotal molecule that links PAF action and neuronal cell migration both in vivo and in vitro.
Different representations of pleasant and unpleasant odours in the human brain
Authors: Rolls Edmund T. , Kringelbach Morten L. , De Araujo Ivan E. T. 
Published: August 2003

AbstractOdours are important in emotional processing; yet relatively little is known about the representations of the affective qualities of odours in the human brain. We found that three pleasant and three unpleasant odours activated dissociable parts of the human brain. Pleasant but not unpleasant odours were found to activate a medial region of the rostral orbitofrontal cortex. Further, there was a correlation between the subjective pleasantness ratings of the six odours given during the investigation with activation of a medial region of the rostral orbitofrontal cortex. In contrast, a correlation between the subjective unpleasantness ratings of the six odours was found in regions of the left and more lateral orbitofrontal cortex. Moreover, a double dissociation was found with the intensity ratings of the odours, which were not correlated with the BOLD signal in the orbitofrontal cortex, but were correlated with the signal in medial olfactory cortical areas including the pyriform and anterior entorhinal cortex. Activation was also found in the anterior cingulate cortex, with a middle part of the anterior cingulate activated by both pleasant and unpleasant odours, and a more anterior part of the anterior cingulate cortex showing a correlation with the subjective pleasantness ratings of the odours. Thus the results suggest that there is a hedonic map of the sense of smell in brain regions such as the orbitofrontal cortex, and these results have implications for understanding the psychiatric and related problems that follow damage to these brain areas.
A novel method of generating neuronal cell lines from gene‐knockout mice to study prion protein membrane orientation
Authors: Holme Andrea , Daniels Maki , Sassoon Judyth , Brown David R. 
Published: August 2003

AbstractThe technology of gene knockout and transgenic mice has allowed the study of the role of genes and their proteins in animal physiology and metabolism. However, these techniques have often been found to be limited in that some genetic manipulations of mice led either to a fatal phenotype or to compensations that mask the loss of function of the target protein. The experimentation on neurons from transgenic mice is particularly critical in the study of key proteins that may be involved in neurodegeneration. The cell fusion technique has been implemented as a novel way to generate cell lines from prion protein knockout mice. Fusion between neonatal mouse neurons and a neuroblastoma cell line have led to a Prnp°/° cell line that facilitates the study of the knockout phenotype. These cells are readily transfectable and allowed us to study the expression of prion protein mutants on a PrP‐knockout background. Using this cell line we have examined the effect of PrP mutations reported to alter PrPc to a transmembrane form. Our results suggest that these mutations do not create transmembrane forms of the protein, but block normal transport of PrP to the cell membrane.
Age‐related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson's disease phenotype
Authors: Thiruchelvam Mona , McCormack Alison , Richfield Eric K. , Baggs Raymond B. , Tank A. William , Di Monte Donato A. , Cory‐Slechta Deborah A. 
Published: August 2003

AbstractWhile advancing age is the only unequivocally accepted risk factor for idiopathic Parkinson's disease, it has been postulated that exposure to environmental neurotoxicants combined with ageing could increase the risk for developing Parkinson's disease. The current study tested this hypothesis by exposing C57BL/6 mice that were 6 weeks, 5 months or 18 months old to the herbicide paraquat, the fungicide maneb or paraquat + maneb, a combination that produces a Parkinson's disease phenotype in young adult mice. Paraquat + maneb‐induced reductions in locomotor activity and motor coordination were age dependent, with 18‐month‐old mice most affected and exhibiting failure to recover 24 h post‐treatment. Three months post‐treatment, reductions in locomotor activity and deficits in motor coordination were sustained in 5‐month‐old and further reduced in 18‐month‐old paraquat + maneb groups. Progressive reductions in dopamine metabolites and dopamine turnover were greatest in 18‐month‐old paraquat + maneb and paraquat groups 3 months post‐treatment. Increased tyrosine hydroxylase enzyme activity compensated for striatal tyrosine hydroxylase protein and/or dopamine loss following treatment in 6‐week‐old and 5‐month‐old, but not 18‐month‐old paraquat and paraquat + maneb mice. Numbers of nigrostriatal dopaminergic neurons were reduced in all age groups following paraquat alone and paraquat + maneb exposure, but these losses, along with decreases in striatal tyrosine hydroxylase protein levels, were progressive in 18‐month‐old paraquat and paraquat + maneb groups between 2 weeks and 3 months post‐exposure. Collectively, these data demonstrate enhanced sensitivity of the ageing nigrostriatal dopamine pathway to these pesticides, particularly paraquat + maneb, resulting in irreversible and progressive neurotoxicity.
The medullary dorsal reticular nucleus enhances the responsiveness of spinal nociceptive neurons to peripheral stimulation in the rat
Authors: Dugast Christophe , Almeida Armando , Lima Deolinda 
Published: August 2003

AbstractSingle‐unit spinal recordings combined with application of glutamate into the medullary dorsal reticular nucleus were used to assess the action of this nucleus upon deep dorsal horn neurons in rats. Injection of high glutamate concentrations (10 and 100 mm) induced a dramatic and long‐lasting increase of the responses of wide‐dynamic range neurons to electrical stimulation of the sciatic nerve in the noxious range, without affecting ongoing discharges. Post‐stimulus time histograms revealed that this increase concerned the post‐discharge, but not A‐ or C‐fibre‐mediated responses, which remained unchanged independently of the stimulation frequency applied. The onset of the glutamate‐induced response enhancement occurred with a concentration‐dependent time delay and developed slowly until its maximum. These data indicate that the medullary dorsal reticular nucleus exerts a facilitating action upon deep dorsal horn wide‐dynamic range neurons by enhancing their capacity to respond to peripheral stimulation through prolongation of their discharge. This action is accompanied by the strengthening of wind‐up of deep dorsal horn wide‐dynamic range neurons, hence providing a plausible substrate for chronic pain states. These results are in agreement with previous behavioural studies suggesting a pronociceptive role for the dorsal reticular nucleus [Almeida et al. (1996) Brain Res. Bull., 39, 7–15; Almeida et al. (1999) Eur. J. Neurosci., 11, 110–122], and support the involvement of a reverberating circuit, previously described in morphological studies [Almeida et al. (1993) Neuroscience, 55, 1093–1106; Almeida et al. (2000) Eur. J. Pain, 4, 373–387], which probably operates only at a certain threshold of activation.
Connexin30‐deficient mice show increased emotionality and decreased rearing activity in the open‐field along with neurochemical changes
Authors: Dere E. , De Souza‐Silva M. A. , Frisch C. , Teubner B. , Söhl G. , Willecke K. , Huston J. P. 
Published: August 2003

AbstractGap‐junction channels in the brain, formed by connexin (Cx) proteins with a distinct regional/cell‐type distribution, allow intercellular electrical and metabolic communication. In astrocytes, mainly the connexins 43, 26 and 30 are expressed. In addition, connexin30 is expressed in ependymal and leptomeningeal cells, as well as in skin and cochlea. The functional implications of the astrocytic gap‐junctional network are not well understood and evidence regarding their behavioural relevance is lacking. Thus, we have tested groups of Cx30−/−, Cx30+/−, and Cx30+/+ mice in the open‐field, an object exploration task, in the graded anxiety test and on the rotarod. The Cx30−/− mice showed reduced exploratory activity in terms of rearings but not locomotion in the open‐field and object exploration task. Furthermore, Cx30−/− mice exhibited anxiogenic behaviour as shown by higher open‐field centre avoidance and corner preference. Graded anxiety test and rotarod performance was similar across groups. The Cx30−/− mice had elevated choline levels in the ventral striatum, possibly related to their aberrant behavioural phenotypes. The Cx30+/− mice had lower dopamine and metabolite levels in the amygdala and ventral striatum and lower hippocampal 5‐hydroxyindole acid (5‐HIAA) concentrations relative to Cx30+/+ mice. Furthermore, the Cx30+/− mice had lower acetylcholine concentrations in the ventral striatum and higher choline levels in the neostriatum, relative to Cx30+/+ mice. Our data suggest that the elimination of connexin30 can alter the reactivity to novel environments, pointing to the importance of gap‐junctional signalling in behavioural processes.
Normal prism adaptation but reduced after‐effect in basal ganglia disorders using a throwing task
Authors: Fernandez‐Ruiz J. , Diaz R. , Hall‐Haro C. , Vergara P. , Mischner J. , Nuñez L. , Drucker‐Colin R. , Ochoa A. , Alonso M. E. 
Published: August 2003

AbstractPrism adaptation is a form of visuomotor learning in which the visual and motor systems need to be adjusted because a visual perturbation is produced by horizontally displacing prisms. Despite being known for over two centuries, the neuronal substrates of this phenomenon are not yet completely understood. In this article the possible role of the basal ganglia in this kind of learning was analysed through a study of Huntington's and Parkinson's disease patients. A throwing technique requiring the use of open loop feedback was used. The variables analysed were visuomotor performance, adaptation rate and magnitude, and the after‐effect. The results clearly showed that both Huntington's and Parkinson's disease groups learned at the same rate as control subjects. In addition, despite having a disturbed visuomotor performance, both experimental groups showed the same adaptation magnitude as the control group. Finally, the after‐effect, which is measured after removing the prisms, is reduced in both patients groups. This reduction leads to a disruption in the normal adaptation–after‐effect correlation found in normal volunteers. These results suggest that basal ganglia are not involved in this type of open‐looped visuomotor learning. The large number of patients studied as well as the similarity of the findings between both populations support this hypothesis. By contrast, there is an impairment in the after‐effect on both basal ganglia patient populations. This impairment may be the result of the deterioration of the perceptual recalibration process involved in visuomotor learning.
Contrasting expression of Kv4.3, an A‐type K+ channel, in migrating Purkinje cells and other post‐migratory cerebellar neurons
Authors: Hsu Yi‐Hua , Huang Hsin‐Yi , Tsaur Meei‐Ling 
Published: August 2003

AbstractKv4.3, an A‐type K+ channel, is the only channel molecule showing anterior–posterior (A–P) compartmentalization in the granular layer of mammalian cerebellum known so far. Kv4.3 mRNA has been detected from the posterior but not anterior granular layer in adult rat cerebellum. To characterize this A‐P compartmentalization further, we examined Kv4.3 protein expression in rat cerebellum by immunohistochemistry at the embryonic, early postnatal and adult stages. Specificity of the Kv4.3 antibody was confirmed by both Western blot and immunoprecipitation analysis. In adulthood, Kv4.3 was detected from the somatodendritic domain of posterior granule cells, with a restriction boundary in the vermal lobule VI extending laterally to the hemispheric crus 1 ansiform lobules. At the early postnatal stage, this A–P pattern first appeared on postnatal day 8, when significant numbers of granule cells had migrated into the posterior granular layer and started to express Kv4.3. Similar Kv4.3 expression in the somatodendritic domain of post‐migratory neurons in the cerebellum was also observed in basket cells, stellate cells, a subset of GABAergic deep neurons, Lugaro cells and, probably, deep Lugaro cells. However, none of them showed A–P compartmentalization. Strikingly, we found Kv4.3 in several clusters of migrating Purkinje cells with mediolateral compartmentalization. These Purkinje cells no longer expressed Kv4.3 after completing the migration. By contrasting the expression in migrating and post‐migratory neurons, our results suggest that Kv4.3 may play an important role in the development of cerebellum, as well as in the mature cerebellum.
Alpha 2 adrenergic receptors on GABAergic, putative sleep‐promoting basal forebrain neurons
Authors: Manns Ian D. , Lee Maan Gee , Modirrousta Mandana , Hou Yiping P. , Jones Barbara E. 
Published: August 2003

AbstractThe basal forebrain plays an important role in the modulation of cortical activity and sleep‐wake states. Yet its role must be multivalent as lesions reportedly diminish cortical fast activity and also cortical slow activity along with slow wave sleep (SWS). Basal forebrain cholinergic vs. GABAergic cell groups could differentially influence these processes. By labelling recorded neurons with Neurobiotin (Nb) using the juxtacellular technique and identifying them by immunostaining, we previously found that whereas all cholinergic cells increased their firing, the majority of GABAergic neurons decreased their firing in association with evoked cortical activation in urethane‐anaesthetized rats. Here, we examined the possibility that such GABAergic, cortical activation ‘off’ cells might bear alpha 2 adrenergic receptors (α2AR) through which noradrenaline (NA) could inhibit them during cortical activation. First using simple dual‐immunostaining for glutamic acid decarboxylase (GAD) and the α2AAR, we found that the majority (≈60%) of GAD‐immunopositive (GAD+) neurons through the magnocellular preoptic nucleus (MCPO) and substantia innominata (SI) were labelled for the α2AAR. Second, in urethane‐anaesthetized rats, we examined whether Nb‐labelled, GAD+ cortical activation ‘off’ neurons that discharged maximally in association with cortical slow wave activity, were immunopositive for α2AAR. We found that all the Nb+/GAD+‘off’ cells were labelled for the α2AAR. Such cells could be inhibited in association with cortical activation and waking when noradrenergic locus coeruleus (LC) neurons discharge and be disinhibited with cortical slow waves and SWS when these neurons become inactive. We thus propose that α2AR‐bearing GABAergic basal forebrain neurons constitute sleep‐active and sleep‐promoting neurons.
Altered responses to orexigenic (AGRP, MCH) and anorexigenic (α‐MSH, CART) neuropeptides of paraventricular hypothalamic neurons in early postnatally overfed rats
Authors: Davidowa Helga , Li Yuzhen , Plagemann Andreas 
Published: August 2003

AbstractFood intake and energy expenditure are regulated by neuropeptides in the hypothalamus. While cocaine‐ and amphetamine‐regulated transcript (CART) peptide and melanocortins such as α‐melanocyte‐stimulating hormone (α‐MSH) are anorexigenic and increase energy expenditure, the endogenous melanocortin receptor antagonist agouti gene‐related protein (AGRP), melanin‐concentrating hormone (MCH) and neuropeptide Y (NPY) are orexigenic, anabolic peptides. Alterations in the regulatory balance may promote excessive weight gain. The action of these peptides on paraventricular hypothalamic neurons was studied in brain slices of overweight, adult rats previously subjected to early postnatal overfeeding in small litters of only three pups per mother, compared to 12 pups per dam in control litters. CART, melanocortins and NPY significantly excited paraventricular neurons of controls, whereas neurons of small‐litter rats were mainly inhibited. Inhibition was dominant following administration of AGRP, MCH and NPY. The altered responses of paraventricular neurons in adult small‐litter rats might reflect a general mechanism of neurochemical plasticity and ‘malprogramming’ of hypothalamic neuropeptidergic systems acquired during the postnatal critical differentiation period, thus leading to permanently altered function of these regulatory systems of body weight.
Low molecular weight constituents of male mouse urine mediate the pregnancy block effect and convey information about the identity of the mating male
Authors: Peele P. , Salazar I. , Mimmack M. , Keverne E. B. , Brennan P. A. 
Published: August 2003

AbstractMouse urine contains a complex mixture of chemosignals including a variety of small volatile molecules that are bound to major urinary proteins. In addition to signalling maleness, male urine also conveys information about individuality, which allows recently mated female mice to distinguish the urinary chemosignals of the mating male from those of an unfamiliar male. The highly polymorphic nature of the major urinary proteins makes them a likely candidate for conveying individuality information in the context of the pregnancy block effect. This was investigated by comparing the pregnancy‐blocking effectiveness of a high molecular weight urinary fraction, containing major urinary proteins, with that of a low molecular weight fraction containing volatile ligands. Not only was the high molecular weight fraction ineffective in blocking pregnancy, but it also appeared to be less important in signalling individuality than the low molecular fraction. The high molecular weight fraction was ineffective in inducing expression of the immediate early gene product egr‐1 in the accessory olfactory bulb. In contrast, the low molecular weight fraction induced egr‐1 expression in the mitral/tufted neurons in the anterior subregion of the accessory olfactory bulb, suggesting that they activate the V1R class of vomeronasal receptor neuron.
Neural activity related to the processing of increasing monetary reward in smokers and nonsmokers
Authors: Martin‐Soelch C. , Missimer J. , Leenders K. L. , Schultz W. 
Published: August 2003

AbstractThis study investigated the processing of increasing monetary reward in nonsmoking and smoking subjects. The choice of the subject populations has been motivated by the observation of differences between nonsmokers and smokers in response to rewarding stimuli in a previous study. Subjects performed a pattern recognition task with delayed response, while rCBF was measured with [\mathrm{H}^{15}_{2}O] PET. Correct responses to the task were reinforced with three different amounts of monetary reward. The subjects received the sum of the rewards at the end of the experiment. The results show that a cortico‐subcortical loop, including the dorsolateral prefrontal cortex, the orbitofrontal cortex, the cingulate gyrus and the thalamus is involved in processing increasing monetary reward. Furthermore, the striatal response differentiates nonsmokers from smokers. Thus, we found significant correlations between rCBF increases in striatum and increasing monetary reward and between striatal rCBF increases and mood in nonsmokers, but not in smokers. Moreover, no significant mood changes among the different monetary rewards could be observed in smokers. We infer that the response of the striatum to reward is related to changes in subjective feelings. The differences between smokers and nonsmokers confirm our previous conclusions that the association between blood flow, performance, mood and amount of reward is more direct in nonsmokers.