bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localization of the glutamate–aspartate transporter, GLAST, in rat taste buds
Authors: Lawton D. Maxwell , Furness David N. , Lindemann Bernd , Hackney Carole M. 
Published: March 2003

AbstractA number of putative neurotransmitter substances have been found in vertebrate taste buds. Amongst these glutamate has been localized in fibres innervating the buds and uptake of glutamate has been shown to occur into receptor cells. It is therefore possible that, in common with other sensory systems, glutamate is a neurotransmitter in taste buds. In the inner ear and retina of mammals, the membranes of supporting cells have been shown to contain the glial glutamate transporter GLAST. In the brain, this protein is involved in glutamate re‐uptake into glial cells where the glutamate is converted into glutamine for recycling into glutamatergic terminals. In this study, the presence of GLAST has been investigated in taste buds in the rat vallate papilla and its distribution compared with that of glutamine to determine whether there are cells in this system that play a glia‐like role in glutamate handling. Immunofluorescent labelling showed that a subset of cells in the taste bud contains GLAST. Immunogold labelling indicated that it occurs in the plasma membranes of supporting cells, especially on the fine cytoplasmic processes of dark cells towards the basal region of the bud. A protein of molecular mass similar to that of cerebellar GLAST was detected in immunoblots of excised papillae. Double labelling and semiquantitative analysis of glutamine and GLAST immunoreactivity showed that the GLAST‐positive cells have a higher level of cytoplasmic glutamine than the adjacent cells. It is proposed that these GLAST‐positive cells play a glia‐like role in the uptake of glutamate following its release at synapses within the taste bud although the precise location of the latter remains uncertain. The GLAST‐positive cells may also be involved in its subsequent conversion to glutamine in a glutamate/glutamine cycle similar to that described in the brain.
O2‐sensing after carotid chemodenervation: hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cells
Authors: Roux Jean‐Christophe , Pequignot Jean‐Marc , Dumas Sylvie , Pascual Olivier , Ghilini Ginette , Pequignot Jacqueline , Mallet Jacques , Denavit‐Saubié Monique 
Published: March 2003

AbstractVentilatory responses to acute and long‐term hypoxia are classically triggered by carotid chemoreceptors. The chemosensory inputs are carried within the carotid sinus nerve to the nucleus tractus solitarius and the brainstem respiratory centres. To investigate whether hypoxia acts directly on brainstem neurons or secondarily via carotid body inputs, we tested the ventilatory responses to acute and long‐term hypoxia in rats with bilaterally transected carotid sinus nerves and in sham‐operated rats. Because brainstem catecholaminergic neurons are part of the chemoreflex pathway, the ventilatory response to hypoxia was studied in association with the expression of tyrosine hydroxylase (TH). TH mRNA levels were assessed in the brainstem by in situ hybridization and hypoxic ventilatory responses were measured in vivo by plethysmography. After long‐term hypoxia, TH mRNA levels in the nucleus tractus solitarius and ventrolateral medulla increased similarly in chemodenervated and sham‐operated rats. Ventilatory acclimatization to hypoxia developed in chemodenervated rats, but to a lesser extent than in sham‐operated rats. Ventilatory response to acute hypoxia, which was initially low in chemodenervated rats, was fully restored within 21 days in long‐term hypoxic rats, as well as in normoxic animals which do not overexpress TH. Therefore, activation of brainstem catecholaminergic neurons and ventilatory adjustments to hypoxia occurred independently of carotid chemosensory inputs. O2‐sensing mechanisms unmasked by carotid chemodenervation triggered two ventilatory adjustments: (i) a partial acclimatization to long‐term hypoxia associated with TH upregulation; (ii) a complete restoration of acute hypoxic responsivity independent of TH upregulation.
Simultaneous movements of upper and lower limbs are coordinated by motor representations that are shared by both limbs: a PET study
Authors: Ehrsson H. Henrik , Naito Eiichi , Geyer Stefan , Amunts Katrin , Zilles Karl , Forssberg Hans , Roland Per E. 
Published: March 2003

AbstractThe purpose of this study was to examine the cerebral control of simultaneous movements of the upper and lower limbs. We examined two hypotheses on how the brain coordinates movement: (i) by the involvement of motor representations shared by both limbs; or (ii) by the engagement of specific neural populations. We used positron emission tomography to measure the relative cerebral blood flow in healthy subjects performing isolated cyclic flexion–extension movements of the wrist and ankle (i.e. movements of wrist or ankle alone), and simultaneous movements of the wrist and ankle (a rest condition was also included). The simultaneous movements were performed in the same directions (iso‐directional) and in opposite directions (antidirectional). There was no difference in the brain activity between these two patterns of coordination. In several motor‐related areas (e.g. the contralateral ventral premotor area, the dorsal premotor area, the supplementary motor area, the parietal operculum and the posterior parietal cortex), the representation of the isolated wrist movement overlapped with the representation of the isolated ankle movement. Importantly, the simultaneous movements activated the same set of motor‐related regions that were active during the isolated movements. In the contralateral ventral premotor cortex, dorsal premotor cortex and parietal operculum, there was less activity during the simultaneous movements than for the sum of the activity for the two isolated movements (interaction analysis). Indeed, in the ventral premotor cortex and parietal operculum, the activity was practically identical regardless whether only the wrist, only the ankle, or both the wrist and the ankle were moved. Taken together, these findings suggest that interlimb coordination is mediated by motor representations shared by both limbs, rather than being mediated by specific additional neural populations.
Induction of neuronal death by α‐synuclein
Authors: Saha Anirban R. , Ninkina Natalia N. , Hanger Diane P. , Anderton Brian H. , Davies Alun M. , Buchman Vladimir L. 
Published: March 2003

AbstractThe molecular and cellular mechanisms underlying neuronal loss in neurodegenerative diseases are unclear. It is generally thought that aggregation of mutated, abnormally modified or abnormally folded proteins leads to the accumulation of extracellular, intracellular or intranuclear deposits that severely compromise cell physiology, leading to the death of the affected neurons. However, there is growing evidence that neuronal apoptosis in the absence of obvious pathological deposits could have a serious impact on the pathogenesis of neurodegenerative diseases. α‐Synuclein has been implicated in aetiology and pathogenesis of certain neurodegenerative diseases, although the precise role of this protein in neurodegeneration is uncertain. The normal functions of α‐synuclein and other members of the synuclein family in the development and function of the nervous system also remain elusive. Here we show that overexpression of wild‐type and mutant forms of α‐synuclein in cultured neurons, but not the closely related persyn (γ‐synuclein), causes apoptosis. These findings suggest that abnormalities of α‐synuclein metabolism could lead to the neuronal loss occurring in certain forms of neurodegeneration before the formation of characteristic pathological lesions.
Constitutive overactivation of protein kinase C in guinea pig brain increases α‐secretory APP processing without decreasing β‐amyloid generation
Authors: Roßner Steffen , Beck Mike , Stahl Tobias , Mendla Klaus , Schliebs Reinhard , Bigl Volker 
Published: March 2003

AbstractWhilst it is generally accepted that the activation of protein kinase C (PKC) increases amyloid precursor protein (APP) secretion in vitro, the role of PKC in the regulation of APP processing and β‐amyloid generation in vivo is still not well understood. In order to address this question, we established the animal model of neocortical microencephalopathy in guinea pigs caused by in utero treatment with methylazoxymethanol acetate, a DNA‐methylating substance that eliminates proliferating cells of neuroepithelial origin. The induction of this neocortical malformation is accompanied by constitutive overactivation of PKC in the neocortex of the offspring. In the cortical and hippocampal tissues of juvenile microencephalic guinea pigs (postnatal day 30), we observed significant increases in basal (by 58% and 74%, respectively,) and phorbol ester‐stimulated PKC enzyme activity (by 47% and 71%) as compared to age‐matched control animals. In the same cortical/hippocampal preparations of methylazoxymethanol‐treated animals, there was increased α‐secretion of APP by 35% and 30% as measured by Western blot analysis using the antibody 6E10, whilst total APP secretion as well as APP mRNA expression remained unaltered. This upregulation of APP α‐secretion was limited to brain areas that displayed elevated PKC activity. However, constitutive overactivation of neocortical PKC did not affect the generation of β‐amyloid peptides 1–40 or 1–42 as measured by ELISA, suggesting that only the α‐secretase pathway of APP processing is affected by chronic PKC overactivation in vivo.
SHORT COMMUNICATIONFetal striatal transplants reinstate the electrophysiological response of pallidal neurons to systemic apomorphine challenge in rats with excitotoxic striatal lesions
Authors: Nakao N. , Nakai K. , Itakura T. 
Published: March 2003

AbstractPrevious studies with single‐unit recording and 2‐[14C]deoxyglucose quantitative autoradiography have shown that systemic administration of apomorphine increases the functional activity of pallidal neurons, and that the enhancement in the globus pallidus (GP) activity is abolished by striatal lesions. The present study employing electrophysiological techniques tested whether embryonic striatal tissue implanted in the excitotoxically damaged striatum of rats may affect the lesion‐induced alteration in the neuronal response of GP to apomorphine. Systemically administered apomorphine significantly increased spontaneously firing rates of GP cells. The blockade of dopamine receptors with haloperidol reversed the increased rate to baseline levels. Quinolinate‐induced striatal lesions attenuated the rate‐increasing effect of apomorphine. Embryonic striatal grafts placed in the lesioned striatum restored the response of GP cells to systemic apomorphine. The graft‐mediated restoration of the GP neuron response to apomorphine were accompanied by an improvement in the motor asymmetry induced by this drug. Considering previous anatomical data to demonstrate extensive innervation of the GP by embryonic striatal grafts, the present results suggest that the grafts reconstruct the functional striatopallidal pathway which is capable of transmitting apomorphine‐induced changes in the neuronal activity.
Differential effects of neurotrophins on ocular dominance plasticity in developing and adult cat visual cortex
Authors: Galuske Ralf A. W. , Kim Dae‐Shik , Castrén Eero , Singer Wolf 
Published: March 2003

AbstractIn the present study we examine the influence of neurotrophins on experience‐dependent synaptic rearrangement in developing and adult visual cortex. Brain‐derived neurotrophic factor (BDNF) or nerve growth factor (NGF) was continuously infused into cortical area 18, and the functional architecture of the cortex was examined by use of optical and electrophysiological recording techniques. In kittens, BDNF infusion during monocular deprivation (MD) reversed the normally occurring ocular dominance (OD) shift towards the non‐deprived eye so that the deprived eye dominated the BDNF‐treated cortex after MD. Under conditions of equal activation of thalamocortical synapses, i.e. when animals were either subject to binocular deprivation (BD) or reared without deprivation, BDNF infusion did not disrupt binocularity of cortical units, but reversed the natural OD bias towards the contralateral eye in favour of the ipsilateral eye. In addition, BDNF treatment in kittens led to a loss of the orientation selectivity of cortical units irrespective of rearing conditions. In adult animals, BDNF influenced neither OD distributions nor orientation selectivity. The effect of NGF was markedly different. It was ineffective in kittens but in adult animals it caused a shift of OD towards the deprived eye when MD was combined with NGF infusion. However, in this case orientation selectivity was preserved. Thus, both neurotrophins have profound activity‐ and age‐dependent effects on the functional architecture of the visual cortex. Moreover, our results indicate that simple substitution of neurotrophins in excess is unlikely to compensate for deprivation effects by preserving or restoring the normal functional architecture of the cortex.
Suppression of c‐fos induction in the nucleus accumbens prevents acquisition but not expression of morphine‐conditioned place preference
Authors: Tolliver Bryan K. , Sganga Michael W. , Sharp Frank R. 
Published: March 2003

AbstractThe c‐fos immediate‐early gene is induced by morphine and other drugs of abuse in the nucleus accumbens (NAc), a mesolimbic region implicated in drug abuse and reward. This study examined the role of c‐fos in the acquisition and expression of the conditioned place paradigm (CPP) in the rat by suppressing Fos protein expression with c‐fos antisense oligodeoxynucleotides (ODNs). CPP was completely prevented by c‐fos antisense ODN infused bilaterally into the NAc prior to each systemic morphine injection, whereas sense and missense NAc injections had no effect on CPP. NAc administration of c‐fos antisense ODN after the last systemic morphine conditioning session did not affect the expression of morphine‐CPP. These results suggest that c‐fos expression in NAc is necessary for the acquisition but not expression of morphine‐CPP, and they have important implications for understanding conditioned behaviours and drug craving and addiction.
Spatiotemporal expression of noncatalytic TrkC NC2 isoform during early and late CNS neurogenesis: a comparative study with TrkC catalytic and p75NTR receptors
Authors: Menn Bénédicte , Timsit Serge , Represa Alfonso , Mateos Stéphanie , Calothy Georges , Lamballe Fabienne 
Published: March 2003

AbstractThe TrkC subfamily of primary high‐affinity neurotrophin‐3 receptors is composed of catalytic (kinase‐containing; TrkC K) and noncatalytic (TrkC NC) isoforms generated by alternative splicing. We previously reported the presence of the mouse noncatalytic TrkC NC2 isoform in regions of neuronal differentiation [Menn, B., Timsit, S., Calothy, G. & Lamballe, F. (1998) J. Comp. Neurol., 401, 47–64]. In order to gain insight into specific roles for TrkC NC2 receptors during CNS neurogenesis, we compared its distribution with that of its catalytic counterparts and the p75NTR receptor in in vivo and in vitro model systems of early and late neuronal differentiation. We found that TrkC NC2 expression coincided with the exit of neuronal progenitors from the cell cycle and was maintained in differentiated cerebellar neurons. We also showed that, whilst TrkC K receptors were expressed both in mitotic and postmitotic cells, TrkC NC2 was present only in differentiating neural stem cell progeny, suggesting its involvement in neuronal and glial cell differentiation. During neuritogenesis of primary neocortical neurons, both TrkC isoforms as well as p75NTR were located in axonal and dendritic processes. However, whilst these various receptors were present in the same neuronal compartments, TrkC NC2 distribution was specifically restricted to distinct areas of extending neurites. Taken together, these findings suggest that spatiotemporal localization of the noncatalytic receptor could account for specific local effects of neurotrophin‐3.
The extracellular matrix molecule tenascin‐R and its HNK‐1 carbohydrate modulate perisomatic inhibition and long‐term potentiation in the CA1 region of the hippocampus
Authors: Saghatelyan Armen K. , Gorissen Silke , Albert Martine , Hertlein Birgit , Schachner Melitta , Dityatev Alexander 
Published: March 2003

AbstractPerisomatic inhibition of pyramidal cells regulates efferent signalling from the hippocampus. The striking presence of HNK‐1, a carbohydrate expressed by neural adhesion molecules, on perisomatic interneurons and around somata of CA1 pyramidal neurons led us to apply monoclonal HNK‐1 antibodies to acute murine hippocampal slices. Injection of these antibodies decreased GABAA receptor‐mediated perisomatic inhibitory postsynaptic currents (pIPSCs) but did not affect dendritic IPSCs or excitatory postsynaptic currents. The decrease in the mean amplitude of evoked pIPSCs by HNK‐1 antibodies was accompanied by an increase in the coefficient of variation of pIPSC amplitude, number of failures and changes in frequency but not amplitude of miniature IPSCs, suggesting that HNK‐1 antibodies reduced efficacy of evoked GABA release. HNK‐1 antibodies did not affect pIPSCs in knock‐out mice deficient in the extracellular matrix molecule tenascin‐R which carries the HNK‐1 carbohydrate as analysed by immunoblotting in synaptosomal fractions prepared from the CA1 region of the hippocampus. For control, HNK‐1 antibody was applied to acute sections of mice deficient in the neural cell adhesion molecule NCAM, another potential carrier of HNK‐1, and resulted in decrease of pIPSCs as observed in wild‐type mice. Reduction in perisomatic inhibition is expected to promote induction of long‐term potentiation (LTP) by increasing the level of depolarization during theta‐burst stimulation. Indeed, LTP was increased by HNK‐1 antibody applied before stimulation. Moreover, LTP was reduced by an HNK‐1 peptide mimic, but not control peptide. These results provide first evidence that tenascin‐R and its associated HNK‐1 carbohydrate modulate perisomatic inhibition and synaptic plasticity in the hippocampus.
Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations
Authors: Hájos N. , Katona I. , Naiem S. S. , Mackie K. , Ledent C. , Mody I. , Freund T. F. 
Published: March 2003

AbstractUsing a new antibody developed against the C‐terminus of the cannabinoid receptor (CB1), the immunostaining in the hippocampus revealed additional axon terminals relative to the pattern reported previously with an N‐terminus antibody. Due to a greater sensitivity of this antibody, a large proportion of boutons in the dendritic layers displaying symmetrical (GABAergic) synapses were also strongly immunoreactive for CB1 receptors, as were axon terminals of perisomatic inhibitory cells containing cholecystokinin. Asymmetrical (glutamatergic) synapses, however, were always negative for CB1. To investigate the effect of presynaptic CB1 receptor activation on hippocampal inhibition, we recorded inhibitory postsynaptic currents (IPSCs) from principal cells. Bath application of CB1 receptor agonists (WIN55,212‐2 and CP55,940) suppressed IPSCs evoked by local electrical stimulation, which could be prevented or reversed by the CB1 receptor antagonist SR141716A. Action potential‐driven IPSCs, evoked by pharmacological stimulation of a subset of interneurons, were also decreased by CB1 receptor activation. We also examined the effects of CB1 receptor agonists on Ca2+‐independent miniature IPSCs (mIPSC). Both agonists were without significant effect on the frequency or amplitude of mIPSCs. Synchronous gamma oscillations induced by kainic acid in the CA3 region of hippocampal slices were reversibly reduced in amplitude by the CB1 receptor agonist CP 55,940, which is consistent with an action on IPSCs. We used CB1–/– knock‐out mice to confirm the specificity of the antibody and of the agonist (WIN55,212‐2) action. We conclude that activation of presynaptic CB1 receptors decreases Ca2+‐dependent GABA release, and thereby reduces the power of hippocampal network oscillations.
Prostaglandin E2‐induced sensitization of bradykinin‐evoked responses in rat dorsal root ganglion neurons is mediated by cAMP‐dependent protein kinase A
Authors: Smith Jacqueline A. M. , Davis Clare L. , Burgess Gillian M. 
Published: March 2003

AbstractPrimary cultures of neonatal rat dorsal root ganglion (DRG) neurons were used to examine the mechanisms underlying both the direct activation and the sensitization of sensory neurons by prostanoids. Prostaglandin E2 (PGE2) elevated cytosolic calcium concentration ([Ca2+]i) in a subpopulation of small (< 19 μm) diameter, capsaicin‐sensitive DRG neurons. PGE2 also stimulated substance P (SP) release from DRG cultures. In contrast to bradykinin, PGE2 did not stimulate phosphoinositidase C (PIC) and the PGE2‐evoked increase in [Ca2+]i was dependent on extracellular calcium. Pre‐treatment with PGE2 potentiated bradykinin‐evoked increases in [Ca2+]i in small diameter neurons and increased the number of cells that responded to low concentrations of bradykinin. A similar effect was seen with prostaglandin I2 (PGI2) but not prostaglandin F2α (PGF2α). PGE2 pretreatment also potentiated bradykinin‐evoked release of SP, inducing a leftward shift in the bradykinin concentration–response curve and an increase in the maximum response. PGE2 stimulated adenylyl cyclase activity in DRG cultures, at concentrations and times consistent with those required to observe both the direct and sensitizing effects of the prostanoid on [Ca2+]i responses. Furthermore, the direct and sensitizing effects of PGE2, on both [Ca2+]i responses and SP release, were mimicked by the membrane permeant cAMP analogue dibutyryl cAMP and inhibited by H89, an inhibitor of cAMP‐dependent protein kinase A (PKA). These observations are consistent with the hypothesis that both direct activation and sensitization of sensory neurons by prostanoids, such as PGE2, are mediated by PKA‐dependent phosphorylation mechanisms.
GDNF enhances the synaptic efficacy of dopaminergic neurons in culture
Authors: Bourque Marie‐Josée , Trudeau Louis‐Eric 
Published: March 2003

AbstractGlial cell line‐derived neurotrophic factor (GDNF) is known to promote the survival and differentiation of dopaminergic neurons of the midbrain. GDNF also causes an enhancement of dopamine release by a mechanism which is presently unclear. Using isolated dopaminergic neurons of the rat ventral tegmental area in culture, we have tested the hypothesis that GDNF regulates the establishment and functional properties of synaptic terminals. Previous studies have shown that single dopaminergic neurons in culture can co‐release glutamate in addition to dopamine, leading to the generation of a fast excitatory autaptic current via glutamate receptors. Using excitatory autaptic currents as an assay for the activity of synapses established by identified dopaminergic neurons, we found that chronically applied GDNF produced a threefold increase in the amplitude of excitatory autaptic currents. This action was specific for dopaminergic neurons because GDNF had no such effect on ventral tegmental area GABAergic neurons. The enhancement of excitatory autaptic current amplitude caused by GDNF was accompanied by an increase in the frequency of spontaneous miniature excitatory autaptic currents. These observations confirmed a presynaptic locus of change. We identified synaptic terminals by using synapsin‐1 immunofluorescence. In single tyrosine hydroxylase‐positive neurons, the number of synapsin‐positive puncta which represent putative synaptic terminals was found to be approximately doubled in GDNF‐treated cells at 5, 10 and 15 days in culture. The number of such morphologically identified terminals in isolated GABAergic neurons was unchanged by GDNF. These results suggest that one mechanism through which GDNF may enhance dopamine release is through promoting the establishment of new functional synaptic terminals.