bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental shift of vanilloid receptor 1 (VR1) terminals into deeper regions of the superficial dorsal horn: correlation with a shift from TrkA to Ret expression by dorsal root ganglion neurons
Authors: Guo A. , Simone D. A. , Stone L. S. , Fairbanks C. A. , Wang J. , Elde R. 
Published: March 2003

AbstractThe cloned vanilloid receptor VR1 can be activated by capsaicin and by thermal stimuli. The pattern of nerve terminals that contain VR1 in adult rat spinal cord does not correspond to axons that arise from a single subset of dorsal root ganglion neurons. Thus, we postulated that the basis underlying this complexity might be better understood from a developmental perspective. First, using capsaicin‐induced hyperalgesia as a measure of VR1 function, we found that vanilloid receptors were functional as early as postnatal day 10 (P10), although hyperalgesia was of longer duration in adult. Interestingly, the appearance of VR1 protein in terminals of dorsal root ganglion neurons shifts over this postnatal period. From embryonic day 16 to P20, the majority of VR1 protein in the spinal cord was observed in lamina I. As animals matured, VR1 protein became more abundant in lamina II, particularly in the inner portion. Consistent with these observations, the number of dorsal root ganglion neurons coexpressing VR1 and isolectin B4 binding sites doubled while the number of neurons that had both VR1 and substance P remained relatively constant from P2 to P10. In peripheral processes, the number of VR1‐positive nerve fibres and terminals in cutaneous structures in postnatal day 10 was half of that in adults. We also show that the association of VR1 with Ret is the reciprocal of the association of VR1 with Trk A. These results suggest that neurotrophins may regulate the extent to which populations of dorsal root ganglion neurons express VR1.
Neuroinflammation‐induced acceleration of amyloid deposition in the APPV717F transgenic mouse
Authors: Qiao Xiaoxi , Cummins David J. , Paul Steven M. 
Published: March 2003

AbstractIt has been postulated that neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease (AD). To directly test whether an inflammatory stimulus can accelerate amyloid deposition in vivo, we chronically administered the bacterial endotoxin, lipopolysaccharide (LPS), intracerebroventricularly (i.c.v.) to 2‐month‐old APPV717F+/+ transgenic (TG) mice, which overexpress a mutant human amyloid precursor protein (APP 717V‐F) with or without apolipoprotein E (apoE) for 2 weeks. Two weeks following central LPS administration a striking global reactive astrocytosis with increased GFAP immunoreactivity was found throughout the brains of all LPS‐treated wild‐type and transgenic mice including the contralateral brain hemisphere. Localized microglial activation was also evident from lectin immunostaining adjacent to the cannula track of LPS‐treated mice. Quantification of thioflavine‐S‐positive Aβ deposits revealed a marked acceleration of amyloid deposition in LPS‐treated APPV717F+/+–apoE+/+ mice compared to nontreated or vehicle‐treated APPV717F+/+–apoE+/+ mice (P = 0.005). By contrast, no amyloid deposits were detected by thioflavine‐S staining in LPS or vehicle‐treated apoE‐deficient APPV717F TG mice. Our data suggest that neuroinflammation can accelerate amyloid deposition in the APPV717F+/+ mouse model of AD and that this process requires the expression of apoE.
ErbB‐4 and neuregulin expression in the adult mouse olfactory bulb after peripheral denervation
Authors: Oberto Michela , Soncin Ilaria , Bovolin Patrizia , Voyron Samuele , De Bortoli Michele , Dati Claudio , Fasolo Aldo , Perroteau Isabelle 
Published: March 2003

AbstractErbB‐4 is expressed by the periglomerular and the mitral/tufted cells of the adult mouse olfactory bulb (OB) and in the present work we tested whether this expression is regulated by the olfactory nerve input to the OB. Reversible zinc sulphate lesions of the olfactory mucosa were made in adult mice and the deafferented OB analysed by immunohistochemistry, Western blotting and semiquantitative RT‐PCR. Following deafferentation, the expression of erbB‐4, erbB‐2 and neuregulin‐1 (NRG‐1) mRNAs in the OB was altered. At early stages (7–14 days) after lesion the levels of expression of olfactory marker protein (OMP), tyrosine hydroxylase (TH), erbB‐4 and NRG‐1 mRNAs were decreased, whilst expression of erbB‐2 increased and that of NRG‐2 was not significantly altered. We observed at least two distinct time courses for these expression changes. The lowest amounts of mRNA for erbB‐4 and NRG‐1 were observed at day 7 after lesion, whilst mRNAs for TH and OMP were lowest at day 14. At day 28 after the lesion, when olfactory receptor neuron axons had reinnervated the olfactory bulb, the expression levels of OMP, TH, erbB‐2, erbB‐4 and NRG‐1 were identical to control values. These results indicate that the expression of erbB‐4 mRNA and protein in periglomerular and mitral cells is controlled by peripheral olfactory innervation. The tight correlation in NRG‐1 and erbB‐4 expression levels also suggests a possible functional link that deserves further exploration.
Calcium currents in rat dentate granule cells are altered after adrenalectomy
Authors: Karst Henk , Joëls Marian 
Published: March 2003

AbstractAdrenal corticosteroid hormones modulate voltage‐gated calcium currents in rat CA1 hippocampal neurons. In the present whole‐cell recording study we examined whether calcium currents in dentate granule cells are also under control of corticosteroids. In a first series of experiments, in which the calcium chelator BAPTA was added to the recording solution, the amplitude of calcium currents induced by a voltage step to −10 mV was found to be enhanced shortly (1 or 2 days) after adrenalectomy compared to sham operation. No enhancement was seen when adrenalectomized animals received a low dose of corticosterone in the drinking water. By contrast, 3 or 7 days after adrenalectomy calcium current amplitude was decreased. Starting 3 days after adrenalectomy, some of the granule cells underwent apoptosis. This caused a bias in the recorded cell population towards relatively apoptosis‐resistant cells, suggesting that restricted calcium influx may be a key feature of cells withstanding the apoptotic route. In accordance, cells from a small percentage (≈ 20%) of animals that resisted apoptosis after adrenalectomy also displayed small calcium currents. In a second series without BAPTA, thus focusing on the endogenous calcium‐buffering capacity, we found that the time constant for the decay of the calcium current was decreased after adrenalectomy, probably due to enhanced calcium‐dependent inactivation of the current. The data indicate that cellular calcium current characteristics of dentate granule cells are altered after adrenalectomy and that the alterations may in part determine the vulnerability to undergo apoptosis.
Involvement of the cerebellar thalamus in human saccade adaptation
Authors: Gaymard B. , Rivaud‐Péchoux S. , Yelnik J. , Pidoux B. , Ploner C. J. 
Published: March 2003

AbstractSaccade adaptation can be experimentally induced by systematically displacing a visual cue during a targeting saccade. Non‐human primate studies have highlighted the crucial role of the cerebellum for saccade adaptation, but its neural substrates in humans are poorly understood. Recent physiological experiments suggest that, in addition to cerebellar structures, cortical areas may be involved as well. We have therefore hypothesized that saccade adaptation may rely on a cerebello‐cerebral network, in which the cerebellar thalamus may link cerebellar and cerebral structures. To test this hypothesis, we studied saccade adaptation in a group of four patients with a thalamic lesion, with (n = 2) or without (n = 2) involvement of the cerebellar thalamus. Compared to healthy subjects, saccade adaptation was reduced in patients with associated cerebellar syndrome, but normal in patients without cerebellar syndrome. These results are consistent with the hypothesis that cerebello‐thalamic pathways contribute to saccade adaptation in humans and suggest that the thalamus relays adaptation‐related information from the cerebellum to cerebral cortical oculomotor areas.
Contact‐dependent aggregation of functional Ca2+ channels, synaptic vesicles and postsynaptic receptors in active zones of a neuromuscular junction
Authors: DiGregorio David A. , Negrete Oscar , Jeromin Andreas , Peng H. Benjamin , Vergara Julio L. 
Published: March 2003

AbstractTo examine whether Ca2+ channels aggregate in a contact‐dependent manner, we characterized the distribution of synaptic vesicles and postsynaptic receptors, and compared it to the location of Ca2+ entry sites, in a Xenopus laevis nerve‐muscle coculture preparation using a localized Ca2+ detection method. The majority (75%) of Ca2+ entry sites at spontaneously formed nerve–muscle contacts were associated with enhanced immunofluorescence to the synaptic vesicle protein, SV2. In contrast, only 11% of recorded sites without Ca2+ transients exhibited significant SV2 immunofluorescence. When comparing the spatial distribution of synaptic markers with that of Ca2+ entry sites, we found that the majority of Ca2+ entry sites (61%) were associated with both enhanced SV2 immunofluorescence and R‐BTX fluorescence, thereby identifying putative neurotransmitter release sites where Ca2+ channels, synaptic vesicles and postsynaptic receptors are colocalized. Using polystyrene beads coated with a heparin binding protein known to mediate in vitro postsynaptic receptor clustering, we show that the location of Ca2+ domains was associated with enhanced SV2 immunofluorescence at neurite‐to‐bead contacts. We conclude that the localization of functional Ca2+ channels to putative active zones follows a contact‐dependent signalling mechanism similar to that known to mediate vesicle aggregation and AChR clustering.
Double‐pulse transcranial magnetic stimulation over the frontal eye field facilitates triggering of memory‐guided saccades
Authors: Wipfli Marius , Felblinger Jacques , Mosimann Urs P. , Hess Christian W. , Schlaepfer Thomas E. , Müri René M. 
Published: March 2003

AbstractThe study investigated the influence of double‐pulse transcranial magnetic stimulation (dTMS) on memory‐guided saccade triggering. Double pulses with interstimulus intervals (ISIs) of 35, 50, 65 or 80 ms were applied over the right frontal eye field (FEF) and as control over the occipital cortex. A significant dTMS effect was found exclusively for contralateral saccades; latency of memory‐guided saccades was reduced after FEF stimulation with an ISI of 50 ms compared to latency without stimulation. This effect proved to be specific for the ISI of 50 ms over the FEF because control stimulation with the same ISI over the occipital cortex had no significant effect on latency of memory‐guided saccades. The results of our study showed that, by using an appropriate ISI, dTMS is able to facilitate contralateral saccade triggering by stimulating the FEF. This suggests that TMS interferes specifically with saccade triggering mechanisms, probably by acting on presaccadic neurons of the FEF.
Intrahippocampal injections of somatostatin dissociate acquisition from the flexible use of place responses
Authors: Lamirault Laëtitia , Guillou Jean‐Louis , Micheau Jacques , Jaffard Robert 
Published: March 2003

AbstractPrevious studies showed that injections of somatostatin (SS‐14) into the hippocampus facilitate the acquisition of spatial tasks in mice. The present study was aimed at better understanding the learning and memory processes that could be affected by hippocampal SS‐14 stimulation. Balb/c mice were submitted to a two‐stage learning paradigm. In stage 1, they were trained for acquisition of a spatial discrimination task in a radial maze and, in stage 2, were submitted to a probe test aiming at evaluating their ability to use flexibly their previously acquired knowledge. Injections of vehicle or SS‐14 were given during the acquisition phase and/or before the probe test using a 2 × 2 factorial design. Mice receiving SS‐14 during acquisition failed to succeed in the probe test despite showing a trend to faster acquisition of the initial spatial discrimination task. By contrast, when given only prior to probe trials, SS‐14 did not yield any behavioural effects. Thus, SS‐14 interfered with the establishment of a flexible form of memory, not with its expression per se, and therefore dissociated the acquisition of place responses from their flexible use. The theoretical issues raised by the present findings are discussed.
Transplantation of neural precursor cells into the dysmyelinated CNS of mutant mice deficient in the myelin‐associated glycoprotein and Fyn tyrosine kinase
Authors: Ader Marius , Schachner Melitta , Bartsch Udo 
Published: March 2003

AbstractWe have studied in long‐term experiments the fate of intraventricularly transplanted neural precursor cells in a dysmyelinated mouse brain. Precursor cells were isolated from striata or spinal cords of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein (EGFP). Cells were expanded in vitro in the presence of mitogens for up to 14 weeks, and injected into the lateral ventricle of young postnatal mouse mutants deficient in the myelin‐associated glycoprotein (MAG) and the nonreceptor‐type tyrosine kinase Fyn. The CNS of these mutants is severely hypomyelinated and most myelin sheaths display ultrastructural abnormalities. Despite this phenotype, MAG/Fyn‐deficient mice have a normal longevity. Analysis of mutant brains 1 to 6 months after transplantation revealed widespread distribution of EGFP‐positive cells in the recipient tissue. Grafted cells preferentially populated white matter tracts and differentiated into a variety of morphologically distinct cell types. A significant fraction of donor cells was identified as oligodendrocytes. Electron microscopic analysis revealed the presence of numerous donor‐derived, ultrastructurally intact, myelin sheaths around host axons. EGFP‐positive oligodendrocytes and myelin survived for up to 6 months after transplantation, the latest time point investigated. Remarkably, the number of donor‐derived oligodendrocytes increased significantly with increasing time intervals after transplantation, resulting in widespread myelination of 6‐month‐old host brains. These long‐term experiments thus demonstrate that extensive myelination of a dysmyelinated brain can be achieved after a single injection of neural precursor cells.
Spatial coding of visual and somatic sensory information in body‐centred coordinates
Authors: Galati Gaspare , Committeri Giorgia , Sanes Jerome N. , Pizzamiglio Luigi 
Published: March 2003

AbstractBecause sensory systems use different spatial coordinate frames, cross‐modal sensory integration and sensory–motor coordinate transformations must occur to build integrated spatial representations. Multimodal neurons using non‐retinal body‐centred reference frames are found in the posterior parietal and frontal cortices of monkeys. We used functional magnetic resonance imaging to reveal regions of the human brain using body‐centred coordinates to code the spatial position of both visual and somatic sensory stimuli. Participants determined whether a visible vertical bar (visual modality) or a location touched by the right index finger (somatic sensory modality) lay to the left or to the right of their body mid‐sagittal plane. This task was compared to a spatial control task having the same stimuli and motor responses and comparable difficulty, but not requiring body‐centred coding of stimulus position. In both sensory modalities, the body‐centred coding task activated a bilateral fronto‐parietal network, though more extensively in the right hemisphere, to include posterior parietal regions around the intraparietal sulcus and frontal regions around the precentral and superior frontal sulci, the inferior frontal gyrus and the superior frontal gyrus on the medial wall. The occipito‐temporal junction and other extrastriate regions exhibited bilateral activation enhancement related to body‐centred coding when driven by visual stimuli. We conclude that posterior parietal and frontal regions of humans, as in monkeys, appear to provide multimodal integrated spatial representations in body‐centred coordinates, and these data furnish the first indication of such processing networks in the human brain.
Neuronal nitric oxide synthase (nNOS) mRNA is down‐regulated, and constitutive NOS enzymatic activity decreased, in thoracic dorsal root ganglia and spinal cord of the rat by a substance P N‐terminal metabolite
Authors: Kovacs Katalin J. , Cai Yongjiu , Larson Alice A. 
Published: March 2003

AbstractNitric oxide (NO) in the spinal cord plays a role in sensory and autonomic activity. Pain induced by acetic acid in the abdominal stretch (writhing) assay and hyperalgesia associated with chronic pain are highly sensitive to NO synthase (NOS) inhibitors. Because substance P (SP) is released and up‐regulated in some models of chronic pain, we hypothesized that an accumulation of SP metabolites may influence NOS expression and activity. To test this hypothesis, we examined the effect of intrathecally (i.t.) injected substance P (1‐7) [SP(1‐7)], the major metabolite of SP in the rat, on neuronal NOS (nNOS) mRNA in the thoracic and lumbar spinal cord, dorsal root ganglia (DRG) and on the corresponding constitutive NOS (cNOS) enzyme activity. Detected using quantitative RT‐PCR, nNOS mRNA content in the thoracic spinal cord was decreased 6 h after injection of 5 µmol of SP(1‐7) and returned to control 2 days later. In thoracic DRG, nNOS mRNA was reduced 48 h after SP(1‐7). The cNOS enzymatic activity in thoracic spinal tissue was gradually decreased to a minimum at 72 h. Down‐regulation of NOS by SP(1‐7) in the thoracic area appears to be highly associated with capsaicin‐sensitive primary afferent neurons. No similar changes in either parameter were measured in the lumbar area after SP(1‐7). These data suggest that N‐terminal SP fragments, which are known to cause long‐term antinociception in the writhing assay, may do so by their ability to down‐regulate NO synthesis along nociceptive pathways.
Four different types of protease‐activated receptors are widely expressed in the brain and are up‐regulated in hippocampus by severe ischemia
Authors: Striggow Frank , Riek‐Burchardt Monika , Kiesel Annett , Schmidt Werner , Henrich‐Noack Petra , Breder Jörg , Krug Manfred , Reymann Klaus G. , Reiser Georg 
Published: March 2003

AbstractA variety of extracellular serine proteases are expressed in the central nervous system or might permeate the blood–brain barrier under pathological conditions. However, their intracerebral targets and physiological functions are largely unknown. Here, we show that four distinct subtypes of protease‐activated receptors (PARs) are abundantly expressed in the adult rat brain and in organotypic hippocampal slice cultures. PAR‐1 expression was significant in the hippocampus, cortex and amygdala. Highest densities of PAR‐2 and PAR‐3 were observed in hippocampus, cortex, amygdala, thalamus, hypothalamus and striatum. Apart from the striatum, a similar localization was found for PAR‐4. Within the hippocampal formation, each PAR subtype was predominantly localized in the pyramidal cell layers. Additionally, we identified PAR‐2 in mossy fibers between dentate gyrus and CA3, PAR‐3 in the subiculum and PAR‐4 in CA3 and in mossy fibres as well as in the stratum lacunosum moleculare. After exposing hippocampal slice cultures to a severe experimental ischemia (oxygen–glucose deprivation), the expression of PARs 1–3 was up‐regulated with subtype‐specific kinetics. The localization of PARs in brain regions particularly vulnerable to ischemic insults as well as distinct alterations in the expression pattern after experimental ischemia support the notion of an important role of extracellular serine proteases and PARs in cerebral ischemia.
Two distinct types of repetitive bursting activity mediated by NMDA in hypothalamic neurons in vitro
Authors: Poulain Pierre 
Published: March 2003

AbstractHypothalamic magnocellular dorsal nucleus neurons were recorded from adult guinea pig brain slices with the whole‐cell patch‐clamp technique to determine the effects of N‐methyl‐d‐aspartate (NMDA) applied in the bath or by iontophoresis. In a majority of cells (59 of 77, 76.6%), rhythmic bursting discharges were evoked by specific activation of NMDA receptors when the membrane was more negative than −60 mV. This endogenous rhythmic activity was resistant to tetrodotoxin. It was suppressed by removal of extracellular Mg2+, indicating the involvement of the voltage‐dependent block of the NMDA channel by Mg2+. Application of thapsigargin showed that rhythmic activity did not depend on the release of Ca2+ from reticulum stores. Blockers of Ca2+ conductances Ni2+ and nifedipine had no effects on the bursts. Their repolarization did not involve the activation of a strophantidin‐ or ouabain‐sensitive pump, but partly depended on an apamine‐sensitive Ca2+‐dependent K+current. In a small subset of cells (9 of 69, 13%), specific activation of NMDA receptors induced another type of bursting activity which consisted of repetitive low‐threshold spikes sustaining bursts of action potentials. Rhythmic low‐threshold spikes subsisted in the presence of tetrodotoxin but were suppressed by Ni2+. Increasing the amount of NMDA brought about a switch from the rhythmic low‐threshold spike burst firing to the rhythmic bursting activity observed for the majority of cells. The present data show for the first time that NMDA receptor activation can induce two independent rhythmic bursting behaviours in the same neuron, probably depending on the strength of the glutamatergic drive.
Glutamate receptor stimulation induces a persistent rhythmicity of the GABAergic inputs to rat midbrain dopaminergic neurons
Authors: Berretta Nicola , Paolucci Egle , Bernardi Giorgio , Mercuri Nicola B. 
Published: March 2003

AbstractThe substantia nigra pars compacta and the ventral tegmental area are part of a complex network in the basal ganglia involved in behaviours as diverse as motor planning, generation of pleasure and drug addiction. Here we report that in the dopaminergic neurons of the rat ventral midbrain a brief coactivation of group I metabotropic and NMDA glutamate receptors may transform a temporally dispersed synaptic GABAergic input into a rhythmic pattern (range 4.5–22.5 Hz), probably through a mechanism involving electrotonic couplings. The plastic and long‐lasting modification in the temporal code of the inhibitory synaptic activity induced by glutamate may be a key element in determining the function of midbrain dopaminergic neurons in both normal and pathological behaviour.