bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic regulation of the recovery of extracellular potassium after seizures in vivo
Authors: Xiong Zhi‐Qi , Stringer Janet L. 
Published: March 2003

AbstractGlial cells are believed to play a major role in the regulation of the extracellular potassium concentration ([K+]o), particularly when the [K+]o is increased. Using ion‐selective electrodes, we compared the [K+]o changes in the dentate gyrus of urethane‐anaesthetized adult rats in the presence of reactive astrocytes and after reduction of glial function. The regulation of [K+]o in the dentate gyrus was determined by measuring the ceiling level of [K+]o and the half‐time of recovery of [K+]o during and after seizures produced by 20 Hz trains of stimulation to the angular bundle. Reactive astrocytes were induced by repeated seizures and their presence was confirmed by a qualitative increase in glial fibrillary acidic protein (GFAP) and vimentin immunoreactivity. To inhibit glial function, fluorocitrate (FC), a reversible metabolic inhibitor, or α‐aminoadipate (α‐AA), an irreversible toxin, was injected into the dentate gyrus region, and the regulation of [K+]o was monitored for 8 h or 2 days later, respectively. After α‐aminoadipate, loss of astrocytes in the dentate gyrus was demonstrated by loss of staining for GFAP. In the presence of reactive astrocytes there was no significant change in the peak [K+]o during seizures or the half‐time of recovery of [K+]o after seizures compared to control animals. α‐Aminoadipate significantly slowed the rate of recovery of [K+]o, but did not change the ceiling [K+]o. Fluorocitrate reversibly decreased the ceiling [K+]o, but also slowed the rate of recovery of [K+]o. Overall our results suggest that normal glial function is required for the recovery of elevated [K+]o after seizures in vivo.
Biochemical and pharmacological evidence of a functional role of AMPA receptors in motor neuron dysfunction in mnd mice
Authors: Mennini T. , Cagnotto A. , Carvelli L. , Comoletti D. , Manzoni C. , Muzio V. , Rizzi M. , Vezzani A. 
Published: March 2003

AbstractWe studied ionotropic glutamate receptor subtypes and the effect of chronic treatment with NBQX [6‐nitro‐7‐sulphamoyl‐benzo(F)quinoxaline‐2,3‐dione], a selective (rs)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor antagonist, in the spinal cord of mnd mice. NBQX (8 mg/kg daily i.p. for 3 weeks starting from 24 weeks old) significantly improved the behavioural scores (hind leg extension reflex, cage rung grasping and gait) in mnd mice, measured after the last drug injection, and increased the number of mice with ‘normal’ gait (from 50% to 90%, P < 0.05).Receptor binding autoradiography of the competitive N‐methyl‐ d‐aspartate (NMDA) antagonist, [3H]CGP 39653, of [3H]AMPA and [3H]kainic acid in spinal cord sections, measured after 1 week of drug washout, were not significantly different in control and mnd mice, and were not modified by NBQX.GluR2/3 immunoreactivity, assessed using Western blotting, was significantly enhanced (by 59%, P < 0.01) in the spinal cord but not in the brain of 28‐week‐old mnd mice compared to age‐matched control mice. NBQX treatment increased GluR2/3 immunoreactivity in the spinal cord of control mice and mnd mice by 327 ± 74% (P < 0.01) and 212 ± 52% (P < 0.01), respectively.The changes in GluR2/3 subunits may involve adaptive mechanisms of the receptor and play some role in the protective effect of NBQX. These findings suggest that selective antagonism of ionotropic non‐NMDA receptors may be of value in the treatment of motor neuron disease.
Satellite‐cell‐derived nerve growth factor and neurotrophin‐3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat
Authors: Zhou Xin‐Fu , Deng Yan‐Shen , Chie Edward , Xue Qing , Zhong Jin‐Hua , McLachlan Elspeth M. , Rush Robert A. , Xian Cory J. 
Published: March 2003

AbstractInjury to a peripheral nerve induces in the dorsal root ganglia (DRG) sprouting of sympathetic and peptidergic terminals around large‐diameter sensory neurons that project in the damaged nerve. This pathological change may be implicated in the chronic pain syndromes seen in some patients with peripheral nerve injury. The mechanisms underlying the sprouting are not known. Using in situ hybridization and immunohistochemical techniques, we have now found that nerve growth factor (NGF) and neurotrophin‐3 (NT3) synthesis is upregulated in satellite cells surrounding neurons in lesioned DRG as early as 48 h after nerve injury. This response lasts for at least 2 months. Quantitative analysis showed that the levels of mRNAs for NT3 and NGF increased in ipsilateral but not contralateral DRG after nerve injury. Noradrenergic sprouting around the axotomized neurons was associated with p75‐immunoreactive satellite cells. Further, antibodies specific to NGF or NT3, delivered by an osmotic mini‐pump to the DRG via the lesioned L5 spinal nerve, significantly reduced noradrenergic sprouting. These results implicate satellite cell‐derived neurotrophins in the induction of sympathetic sprouting following peripheral nerve injury.
Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin
Authors: Koltzenburg Martin , Bennett David L. H. , Shelton David L. , McMahon Stephen B. 
Published: March 2003

AbstractEvidence suggests that nerve growth factor (NGF) is an important mediator in inflammatory pain states: NGF levels increase in inflamed tissue, and neutralization of endogenous NGF prevents the hyperalgesia which normally develops during inflammation of the skin. Here we asked whether NGF contributes to sensitization of primary afferent nociceptors, which are an important component of pain and hyperalgesia in inflamed tissue. An in vitro skin nerve preparation of the rat was used to directly record the receptive properties of thin myelinated (Aδ) and unmyelinated (C) nociceptors innervating normal hairy skin, carrageenan‐inflamed skin and carrageenan‐inflamed skin where endogenous NGF had been neutralized by application of a trkA‐IgG (tyrosine kinase Aimmunoglobulin G) fusion molecule. Following carrageenan inflammation, there was a marked increase in the proportion of nociceptors which displayed ongoing activity (50% of nociceptors developed spontaneous activity compared to 4% of nociceptors innervating normal uninflamed skin), and this was reflected in a significant increase in the average ongoing discharge activity. Spontaneously active fibres were sensitized to heat and displayed a more than twofold increase in their discharge to a standard noxious heat stimulus. Furthermore, the number of nociceptors responding to the algesic mediator bradykinin increased significantly from 28% to 58%. By contrast, the mechanical threshold of nociceptive afferents did not change during inflammation. When the NGF‐neutralizing molecule trkA‐IgG was coadministered with carrageenan at the onset of the inflammation, primary afferent nociceptors did not sensitize and displayed essentially normal response properties, although the inflammation as evidenced by tissue oedema developed normally. We therefore conclude that NGF is a crucial component for the sensitization of primary afferent nociceptors associated with tissue inflammation.
Regrowth of axons into the distal spinal cord through a Schwann‐cell‐seeded mini‐channel implanted into hemisected adult rat spinal cord
Authors: Xu Xiao Ming , Zhang Shu‐Xin , Li Huaying , Aebischer Patrick , Bunge Mary Bartlett 
Published: March 2003

AbstractSchwann cells (SCs) have been shown to be a key element in promoting axonal regeneration after being grafted into the central nervous system (CNS). In the present study, SC‐supported axonal regrowth was tested in an adult rat spinal cord implantation model. This model is characterized by a right spinal cord hemisection at the eighth thoracic segment, implantation of a SC‐containing mini‐channel and restoration of cerebrospinal fluid circulation by suturing the dura. We demonstrate that a tissue cable containing grafted SCs formed an effective bridge between the two stumps of the hemicord 1 month after transplantation. Approximately 10 000 myelinated and unmyelinated axons (1 : 9) per cable were found at its midpoint. In addition to propriospinal axons and axons of peripheral nervous system (PNS) origin, axons from as many as 19 brainstem regions also grew into the graft without additional treatments. Most significantly, some regenerating axons in the SC grafts were able to penetrate through the distal graft–host interface to re‐enter the host environment, as demonstrated by anterograde axonal labelling. These axons coursed toward, and then entered the grey matter where terminal bouton‐like structures were observed. In channels containing no SCs, limited axonal growth was seen within the graft and no axons penetrated the distal interface. These findings further support the notion that SCs are strong promotors of axonal regeneration and that the mini‐channel model may be appropriate for further investigation of axonal re‐entry, synaptic reconnection and functional recovery following spinal cord injury.
IPSPs elicited in CA1 pyramidal cells by putative basket cells in slices of adult rat hippocampus
Authors: Ali Afia B. , Bannister A. Peter , Thomson Alex M. 
Published: March 2003

AbstractCA1 basket cells are identifiable by an axonal arbour largely confined to, and spanning, the entire depth of stratum pyramidale where they innervate pyramidal somata and proximal dendrites. Basket cells display a range of electrophysiological properties and the inhibitory postsynaptic potentials (IPSPs) they elicit in pyramidal cells vary widely in duration. To determine whether these parameters are correlated, we used paired intracellular recordings, with biocytin filling, in pyramidal cells of adult hippocampal slices, and studied γ‐aminobutyric acid (GABAA) IPSPs (n = 43) elicited by putative basket cells (n = 35) with axons largely confined to stratum pyramidale in simultaneously recorded pyramidal cells. Fast‐spiking interneurons elicited relatively brief IPSPs, while IPSPs elicited by burst‐firing cells were amongst the slowest. Regular spiking interneurons elicited fast and slow GABAA IPSPs, but any one interneuron elicited IPSPs with remarkably similar durations in two to four pyramidal targets. However, with different types of target for a single putative basket cell, IPSPs elicited in postsynaptic interneurons were briefer than in pyramidal cells. Vertical oriens cells with somata in stratum oriens and a narrow, sparse axonal arbour in stratum pyramidale in transverse hippocampal slices, elicited IPSPs whose rise times and half widths clustered around intermediate values. Durations of IPSPs in pyramidal cells thus correlate, to a degree, with the physiological properties of presynaptic basket cells. The seven‐fold range of durations observed (10–70 ms half widths) may underlie contributions made by different basket cells to hippocampal rhythms of different frequencies.
Hippocampal plasticity in Alzheimer's disease: changes in highly polysialylated NCAM immunoreactivity in the hippocampal formation
Authors: Mikkonen Mia , Soininen Hilkka , Tapiola Tero , Alafuzoff Irina , Miettinen Riitta 
Published: March 2003

AbstractThe highly polysialylated neural cell adhesion molecule (PSA‐NCAM) is one of the most promising molecules that contributes to plasticity in the central nervous system. We evaluated PSA‐NCAM immunoreactivity in the hippocampal formation of Alzheimer's disease (AD) patients. We found significant increases over control levels in the optical density ratios of PSA‐NCAM immunoreactivity in the outer molecular layer/granule cell layer (ODoml/grl) and in the inner molecular layer/granule cell layer (ODiml/grl) in the dentate gyrus of AD patients. The optical density of the granule cell layer in the dentate gyrus did not differ significantly between AD patients and control subjects. However, the number of PSA‐NCAM‐immunopositive infragranule cells was higher in the AD group compared with control subjects. The major finding in the CA1, subiculum and entorhinal cortex of AD patients was the disorganization of PSA‐NCAM‐immunoreactive fibres. These results indicate that neuronal remodelling occurs, especially in the dentate gyrus of patients with AD.
Investigation by ion channel domain transplantation of rat glutamate receptor subunits, orphan receptors and a putative NMDA receptor subunit
Authors: Villmann Carmen , Strutz Nathalie , Morth Tanja , Hollmann Michael 
Published: March 2003

AbstractAmong the 18 ionotropic glutamate receptor subunits identified in the mammalian central nervous system, five (delta1, delta2, GluR7, chi2 and NR3A, formerly called NMDAR‐L or chi1) reportedly fail to form functional ion channels in heterologous expression systems. Four of these subunits, delta1, delta2, chi2 and NR3A, have not even been shown to bind glutamatergic ligands, relegating them to the status of ‘orphan’ receptors. We used a domain transplantation approach to investigate potential functional properties of the putative ion channel domains of four of these subunits. By exchanging ion pore domains between functional glutamate receptors (GluR1, GluR6 and NMDAR1) with known pore properties we first tested the feasibility of the domain swapping method. We demonstrate that ion channel domains can be transplanted between all three functional subfamilies of ionotropic glutamate receptors. Furthermore, exchange of ion pore domains allows identification of those channel properties determined exclusively by the ion pore. We then show that transplanting the pore domain of GluR7 into either GluR1 or GluR6 generates perfectly functional ligand‐gated ion channels that allow characterization of electrophysiological and pharmacological properties of the GluR7 pore domain. In contrast, delta1, delta2 and NR3A do not produce functional receptors when their pore domains are transplanted into either the AMPA receptor, GluR1, the kainate receptor, GluR6, or the NMDA receptor, NMDAR1. We speculate that the orphan receptors delta1 and delta2, and the NMDA receptor‐like subunit NR3A may serve some modulatory function, rather than contributing to the formation of ion channels.
Release properties and functional integration of noradrenergic‐rich tissue grafted to the denervated spinal cord of the adult rat
Authors: Leanza G. , Cataudella T. , Dimauro R. , Monaco S. , Stanzani S. 
Published: March 2003

AbstractNoradrenaline‐ (NA‐) containing grafts of central (embryonic locus coeruleus, LC) or peripheral (juvenile adrenal medullary, AM, autologous superior cervical ganglionic, SCG) tissue were implanted unilaterally into rat lumbar spinal cord previously depleted of its NA content by 6‐hydroxydopamine (6‐OHDA) intraventricularly. A microdialysis probe was implanted in the spinal cord 3–4 months after transplantation, and extracellular levels of noradrenaline were monitored in freely moving animals during basal conditions and following administration of pharmacological or behavioural stimuli. Age‐matched normal and lesioned animals both served as controls. Morphometric analyses were carried out on horizontal spinal sections processed for dopamine‐β‐hydroxylase (DBH) immunocitochemistry, in order to assess lesion‐ or graft‐induced changes in the density of spinal noradrenergic innervation, relative to the normal patterns. In lesioned animals, the entire spinal cord was virtually devoid of DBH‐positive fibers, resulting in a dramatic 88% reduction in baseline NA, compared with that in controls, which did not change in response to the various stimuli. LC and SCG grafts reinstated ≈ 80% and 50% of normal innervation density, respectively, but they differed strikingly in their release ability. Thus, LC grafts restored baseline NA levels up to 60% of those in controls, and responded with significantly increased NA release to KCl‐induced depolarization, neuronal uptake blockade and handling. In contrast, very low NA levels and only poor and inconsistent responses to the various stimuli were observed in the SCG‐grafted animals. In AM‐grafted animals, spinal extracellular NA levels were restored up to 45% of those in controls, probably as a result of nonsynaptic, endocrine‐like release, as grafted AM cells retained the chromaffine phenotype, showed no detectable fibre outgrowth and did not respond to any of the pharmacological or behavioural challenges. Thus, both a regulated, impulse‐dependent, and a diffuse, paracrine‐like, NA outflow may play roles in the recovery of lesion‐induced sensory and/or motor impairments previously reported with these types of grafts following transplantation into the severed spinal cord.
μ‐ and δ‐opioid receptor agonists inhibit DARPP‐32 phosphorylation in distinct populations of striatal projection neurons
Authors: Lindskog Maria , Svenningsson Per , Fredholm Bertil , Greengard Paul , Fisone Gilberto 
Published: March 2003

AbstractIn the striatum, DARPP‐32 (dopamine‐ and cAMP‐regulated phosphoprotein of 32 kDa) is highly expressed by virtually all projection medium‐sized spiny neurons. cAMP‐dependent phosphorylation of DARPP‐32 is stimulated via activation of dopamine D1 receptors in striatonigral neurons, and via activation of adenosine A2A receptors in striatopallidal neurons. In this study, we have examined the contribution of μ‐, δ‐ and κ‐opioid receptors to the regulation of DARPP‐32 phosphorylation, in rat striatal slices. The results show that, at low concentrations (100 pm–1 nm), the μ‐opioid agonist, Tyr‐D‐Ala‐Gly‐N‐Me‐Phe‐glycinol (DAMGO), inhibits the increase in DARPP‐32 phosphorylation induced by activation of D1, but not by activation of A2A receptors. Conversely, the δ‐receptor agonist, Tyr‐D‐Pen‐Gly‐Phe‐D‐Pen (DPDPE), inhibits DARPP‐32 phosphorylation induced by activation of A2A, but not by activation of D1 receptors. The κ‐receptor agonist, U50488, does not affect DARPP‐32 phosphorylation induced by either D1 or A2A agonists. Thus, μ‐opioid receptors interact with dopamine D1 receptors on striatonigral neurons, whereas δ‐opioid receptors interact with adenosine A2A receptors on striatopallidal neurons. These results suggest that regulation of DARPP‐32 phosphorylation is involved in mediating some of the effects exerted by enkephalin on striatal medium‐sized spiny neurons.
Observation and execution of movement: similarities demonstrated by quantified electroencephalography
Authors: Cochin Stéphanie , Barthelemy Catherine , Roux Sylvie , Martineau Joëlle 
Published: March 2003

AbstractQuantified electroencephalography (qEEG) was used to compare cerebral electrical variations while human subjects (10 males and 10 females) were observing and executing finger movements and while they were resting. Video recording enabled elimination of subjects performing involuntary movements. EEGs were recorded from 14 sites in seven frequency bands: theta 1, theta 2, alpha 1, alpha, beta 1, beta 2 and beta 3. Analyses were performed on logarithmically transformed absolute spectral power values. Both observation and execution of finger movements involved a decrease in spectral power compared with resting. This decrease was significant only for the alpha 1 frequency band (7.5–10.5 Hz) and it involved nine of the 14 electrode locations (F7, F8, F4, T6, T5, C3, C4, P3 and P4). This indicates that the motor cortex and the frontal cortex are specifically activated by both observation and execution of finger movements. These results provide evidence that observation and execution of movement share the same cortical network.
Amyloid precursor protein of Alzheimer's disease: evidence for a stable, full‐length, trans‐membrane pool in primary neuronal cultures
Authors: Storey Elsdon , Katz Melissa , Brickman Yardenah , Beyreuther Konrad , Masters Colin. L. 
Published: March 2003

AbstractWe and colleagues have shown that the amyloid protein precursor of Alzheimer's disease (APP) is distributed along the surface of neurites of fixed but nonpermeabilized neurons in primary culture in a segmental pattern, which shows colocalization with some markers of adhesion patches. This is in contrast to the diffuse pattern of immunoreactivity seen after permeabilization. We have also recently demonstrated that the APP in these surface patches is likely to be integral to the membrane rather than secreted and re‐adsorbed, based on alkali stripping experiments and on soluble APP adsorption experiments. Total cellular APP has previously been shown to have a short half‐life of ≈ 30–60 min. We confirm this in neurons in primary culture in pulse‐chase experiments using short labelling times. Additionally, we provide evidence that a separate, stable pool of neuronal APP can be demonstrated in pulse‐chase experiments using long labelling times. Experiments involving inhibition of protein synthesis suggest that this corresponds with the surface, segmental pool. Metabolic labelling followed by surface biotinylation and two‐stage precipitation demonstrates that the surface APP is trans‐membrane and full‐length (not carboxyl‐terminal truncated), and confirms that the surface APP belongs to the stable pool. This two‐stage procedure is necessary as the surface APP appears to be present in low copy number, and is difficult to detect by direct labelling. This information is consistent with a role for APP in stable cell‐matrix or cell–cell interactions.
Autoradiographic studies of 5‐HT1A‐receptor‐stimulated [35S]GTPγS‐binding responses in the human and monkey brain
Authors: Dupuis Delphine S. , Pauwels Petrus J. , Radu Diana , Hall Håkan 
Published: March 2003

AbstractG‐protein activation mediated by serotonin 5‐HT1A receptors in human and monkey brain was investigated by using quantitative autoradiography of agonist‐stimulated [35S]GTPγS binding to whole‐hemisphere brain sections. [35S]GTPγS binding was stimulated by the mixed 5‐HT1A/1B/1D agonist L 694247 (10 μm) in human brain regions enriched in 5‐HT1A binding sites [e.g. hippocampus (132–137%), superficial layers of the neocortex (37–61%), and cingulate and entorhinal cortex (34 and 32%, respectively)]. L 694247 caused virtually no stimulation in regions with 5‐HT1B/1D receptors, such as substantia nigra, caudate nucleus and putamen. Similar results were obtained with monkey brain sections. The L 694247‐mediated [35S]GTPγS‐binding responses in human and monkey brain sections were antagonized by the selective, silent 5‐HT1A antagonist WAY 100635 (10 μm). The 5‐HT1B inverse agonist SB 224289 (10 μm) did not affect the [35S]GTPγS‐binding response of L 694247. The distribution pattern of the [35S]GTPγS‐binding response and the antagonist profile suggest the L 694247‐induced response in human and monkey brain is mediated by 5‐HT1A receptors. A weak stimulation of [35S]GTPγS binding was also observed in human hippocampus with either 10 μm 8‐OH‐DPAT (25 ± 4%) or naratriptan (42 ± 2%) compared with that obtained with L 694247. In conclusion, G‐protein activation by 5‐HT1A receptors can be measured in human and monkey brain sections. L 694247 appears to possess higher efficacy at 5‐HT1A receptors compared with 8‐OH‐DPAT and naratriptan.