bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mouse model of familial amyotrophic lateral sclerosis expressing a mutant superoxide dismutase 1 shows evidence of disordered transport in the vasopressin hypothalamo‐neurohypophysial axis
Authors: de Aguilar José‐Luis González , Gordon Jon W. , René Frédérique , Lutz‐Bucher Bernadette , Kienlen‐Campard Pascal , Loeffler Jean‐Philippe 
Published: March 2003

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal, paralytic disorder that primarily affects motoneurons. By combining physiological and morphological approaches, we examined the effect of a murine superoxide dismutase 1 (SOD1) mutation (G86R), which induces neurological disorders resembling human familial ALS (FALS), on the arginine vasopressin (AVP) hypothalamo‐neurohypophysial axis, an unmyelinated tract poor in neurofilaments. First, we observed that G86R mice progressively consumed more water than wild‐type littermates. Furthermore, levels of plasma AVP and neurohypophysial AVP content were decreased in the SOD1 mutant mice, whereas the amount of hypothalamic AVP increased in an age‐dependent manner. However, hypothalamic AVP mRNA levels were not significantly modified in these animals. At the ultrastructural level, we found that the neurohypophysis of G86R mice had a decreased number of neurosecretory axons. Conversely, the presence of large axon swellings was more pronounced in the SOD1 mutant mice. In addition, the size of neurosecretory granules was higher in G86R than in wild‐type animals. All these findings strongly suggest that the FALS‐associated SOD1 mutation injures the hypothalamo‐neurohypophysial axis by provoking early, progressive disturbances in the axonal transport of neurosecretory products from neuronal perikarya to nerve terminals. This blockade could ultimately result in degeneration of the tract, as proposed for the myelinated, neurofilament‐enriched motor axons affected by ALS.
Distinct kinetics of cloned T‐type Ca2 +  channels lead to differential Ca2 +  entry and frequency‐dependence during mock action potentials
Authors: Kozlov Andrei S. , McKenna Frank , Lee Jung‐Ha , Cribbs Leanne L. , Perez‐Reyes Edward , Feltz Anne , Lambert Régis C. 
Published: March 2003

AbstractVoltage‐dependent activity around the resting potential is determinant in neuronal physiology and participates in the definition of the firing pattern. Low‐voltage‐activated T‐type Ca2 +  channels directly affect the membrane potential and control a number of secondary Ca2 + ‐dependent permeabilities. We have studied the ability of the cloned T‐type channels (α1G,H,I) to carry Ca2 +  currents in response to mock action potentials. The relationship between the spike duration and the current amplitude is specific for each of the T‐type channels, reflecting their individual kinetic properties. Typically the charge transfer increases with spike broadening, but the total Ca2 +  entry saturates at different spike durations according to the channel type: 4 ms for α1G; 7 ms for α1H; and >  10 ms for α1I channels. During bursts, currents are inhibited and/or transiently potentiated according to the α1 channel type, with larger effects at higher frequency. The inhibition may be induced by voltage‐independent transitions toward inactivated states and/or channel inactivation through intermediate closed states. The potentiation is explained by an acceleration in the channel activation kinetics. Relatively fast inactivation and slow recovery limit the ability of α1G and α1H channels to respond to high frequency stimulation ( >  20 Hz). In contrast, the slow inactivation of α1I subunits allows these channels to continue participating in high frequency bursts (100 Hz). The biophysical properties of α1G, H and I channels will therefore dramatically modulate the effect of neuronal activities on Ca2 +  signalling.
Manipulation of synaptic sign and strength with divalent cations in the vertebrate retina: pushing the limits of tonic, chemical neurotransmission
Authors: Piccolino Marco , Vellani Vittorio , Rakotobe Liramalala A. , Pignatelli Angela , Barnes S. , McNaughton Peter 
Published: March 2003

AbstractAt the first synaptic level of the vertebrate retina, photoreceptor light responses are transmitted to second order neurones through a chemical synapse based on a tonic release of neurotransmitter modulated by graded changes of presynaptic potential. The possibility that such synapses could work through a Ca2+‐independent process had been proposed by previous authors, based on the persistence of transmission process in low Ca2+ media containing Co2+ or Ni2+ ions. Recently, we were able to explain these results within the framework of the classical calcium‐hypothesis of synaptic transmission by taking into account the modifications of presynaptic surface potential brought about by changes of divalent cation concentrations. Here we report data showing how a surface‐charge hypothesis could account for several apparently paradoxical effects of divalent cation manipulations such as: the enhancement of neurotransmitter release induced by low Ca2+ media; the transmission "unblocking" effect of Zn2+, Co2+ and Ni2+; and the reversal of transmission polarity induced by application of low Ca2+ media containing Cd2+ or Mg2+ ions.
Modulation of feeding‐induced activation of mesolimbic dopamine transmission by appetitive stimuli and its relation to motivational state
Authors: Bassareo Valentina , Di Chiara Gaetano 
Published: March 2003

AbstractWe have previously shown in non‐deprived rats that feeding of an unfamiliar palatable food (Fonzies®) phasically stimulates in vivo dopamine (DA) transmission in the medial nucleus accumbens (NAc) and this effect undergoes habituation after a previous (24 h) Fonzies meal (Bassareo & Di Chiara 1997, J. Neurosci., 17, 851–861). The present study shows that an unfamiliar food (Kinder®) with a taste and composition (milk chocolate) different from that of Fonzies, also induces a release of DA in the NAc subjected to one‐trial habituation. Habituation was taste specific as no cross‐habituation was observed between Fonzies and Kinder. In undeprived rats, a 40‐min exposure to an intrinsic appetitive stimulus (food smell arising from a Fonzies‐filled plastic box) also prevented the increase in dialysate DA associated with Fonzies feeding, and this effect was partially reversed by food deprivation. Food deprivation also prevented habituation of Fonzies‐induced increase of dialysate DA in the NAc. Predictive association of an empty plastic box to Fonzies feeding resulted in the acquisition of appetitive properties by the box and in facilitation (rather than inhibition) of the phasic responsiveness of DA transmission to Fonzies feeding. A 10‐min pre‐exposure to appetitive olfactory stimuli intrinsic to Fonzies still prevented, like a 40‐min pre‐exposure, the NAc DA response to Fonzies feeding; however, a 5‐min pre‐exposure to these appetitive stimuli did not prevent the DA response in the NAc. These results show that the phasic responsiveness of NAc DA transmission to an unfamiliar palatable food is under strong modulatory control by primary (consummatory) and secondary (appetitive) stimuli, and that the sign and extent of this control depends on the nature of the appetitive stimulus, delay of reward and motivational state (deprivation).
Neurochemical gradients along monkey sensory cortical pathways: calbindin‐immunoreactive pyramidal neurons in layers II and III
Authors: Kondo Hideki , Tanaka Keiji , Hashikawa Tsutomu , Jones Edward G. 
Published: March 2003

AbstractWe examined the distribution of neurons containing immunoreactivity for three calcium‐binding proteins, calbindin, parvalbumin and calretinin, as well as nonphosphorylated neurofilament protein, in cortical areas along the ventral and dorsal cortical visual pathways, and in ventrally‐directed somatosensory and auditory cortical pathways. Calbindin‐immunoreactive pyramidal neurons showed the most prominent regional differences. They were largely restricted to layers II and III and their number monotonically increased from the primary sensory areas to the anteroventral areas along the ventral visual pathway and along the ventrally‐directed somatosensory and auditory pathways. The number of calbindin‐immunoreactive pyramidal neurons in layers II and III also increased along the dorsal visual pathway, but the number in the last recognized stage of the dorsal visual pathway (area 7a) was significantly smaller than that at the corresponding stage in the ventral visual pathway (TE). The number of calbindin‐immunoreactive pyramidal neurons was highest in layers II and III of areas 35/36, TG, and TF/TH, which represent terminal cortical regions of the pathways. These results show neurochemical differences between cortical areas located at early and late stages along serial corticocortical pathways, as well as confirming differences between pyramidal neurons in the supragranular and infragranular layers.
Induction of hypoxia‐inducible factor‐1 (HIF‐1) and its target genes following focal ischaemia in rat brain
Authors: Bergeron Marcelle , Yu Aimee Y. , Solway Karen E. , Semenza Gregg L. , Sharp Frank R. 
Published: March 2003

AbstractHIF‐1 is a heterodimeric transcription factor, induced by hypoxia, that is composed of HIF‐1α and HIF‐1β protein subunits. It binds to promoter/enhancer elements and stimulates the transcription of hypoxia‐inducible target genes, including glucose transporter‐1 and the glycolytic enzymes. Because HIF‐1 activation might promote cell survival in hypoxic tissues, we studied the effect of permanent middle cerebral artery occlusion on the expression of HIF‐1α, HIF‐1β and several HIF‐1 target genes in adult rat brain. After focal ischaemia, mRNAs encoding HIF‐1α, glucose transporter‐1 and several glycolytic enzymes were up‐regulated in the peri‐infarct penumbra. This was observed by 7.5 h after the onset of ischaemia and increased further at 19 and 24 h. Regional cerebral blood flow was moderately decreased at 1 and 24 h after the ischaemia in areas of HIF‐1 and HIF‐1 target gene induction. Because hypoxia induces HIF‐1 in other tissues, systemic hypoxia (6% O2 for 4.5 h) was also shown to increase HIF‐1α protein expression in the adult rat brain. It is proposed that decreased blood flow to the penumbra decreases the supply of oxygen and that this induces HIF‐1 and its target genes. This is the first study to show induction of HIF‐1 after focal ischaemia in brain. Increased expression of HIF‐1 target genes as a result of HIF‐1 activation by hypoxia may contribute to tissue viability in the hypoxic/ischaemic penumbra by increasing glucose transport and glycolysis.
Encoding of target direction and speed during visual instruction and arm tracking in dorsal premotor and primary motor cortical neurons
Authors: Johnson M. T. V. , Coltz J. D. , Ebner T. J. 
Published: March 2003

AbstractThe encoding of direction and speed in the discharge of dorsal premotor (PMd) and primary motor (MI) neurons was studied during two‐dimensional visually‐instructed pursuit arm movements in which eight directions and four constant speeds were independently manipulated. Each trial consisted of equal durations of visual observation of target movement without hand movement (cue) and visual pursuit‐tracking of the target with the hand (track). A total of 240 neurons was recorded from PMd and MI in two Macaca mulatta monkeys. Two classes of regression analyses were used to relate neuronal firing during the cue and track periods to direction and speed. First, the average firing from each period was fitted to target direction or speed. Period‐averaged firing significantly correlated with direction more frequently in the track than in the cue period. Conversely, correlations with speed (with or without direction) were more common in the cue than in the track period. Secondly, a binwise regression evaluated the temporal evolution of firing correlations with direction and speed. Supporting the period‐based results, significant binwise correlations of the discharge with speed occurred preferentially during the cue period when there was no hand movement. Prior to movement, correlations of the firing with direction became significant and continued through the movement. Both analyses demonstrated a distinct tendency for neurons to be modulated by speed information early and by direction information later. This temporal parcellation reflects both the sequential demands of the task and constraints placed on the neural computations. The early representation of target speed is hypothesized to reflect the need to calculate a ‘go signal’ for the initiation of movement.
Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain
Authors: Marsicano Giovanni , Lutz Beat 
Published: March 2003

AbstractCannabinoids can modulate motor behaviour, learning and memory, cognition and pain perception. These effects correlate with the expression of the cannabinoid receptor 1 (CB1) and with the presence of endogenous cannabinoids in the brain. In trying to obtain further insights into the mechanisms underlying the modulatory effects of cannabinoids, CB1‐positive neurons were determined in the murine forebrain at a single cell resolution. We performed a double in situ hybridization study to detect mRNA of CB1 in combination with mRNA of glutamic acid decarboxylase 65k, neuropeptide cholecystokinin (CCK), parvalbumin, calretinin and calbindin D28k, respectively. Our results revealed that CB1‐expressing cells can be divided into distinct neuronal subpopulations. There is a clear distinction between neurons containing CB1 mRNA either at high levels or low levels. The majority of high CB1‐expressing cells are GABAergic (γ‐aminobutyric acid) neurons belonging mainly to the cholecystokinin‐positive and parvalbumin‐negative type of interneurons (basket cells) and, to a lower extent, to the calbindin D28k‐positive mid‐proximal dendritic inhibitory interneurons. Only a fraction of low CB1‐expressing cells is GABAergic. In the hippocampus, amygdala and entorhinal cortex area, CB1 mRNA is present at low but significant levels in many non‐GABAergic cells that can be considered as projecting principal neurons. Thus, a complex mechanism appears to underlie the modulatory effects of cannabinoids. They might act on principal glutamatergic circuits as well as modulate local GABAergic inhibitory circuits. CB1 is very highly coexpressed with CCK. It is known that cannabinoids and CCK often have opposite effects on behaviour and physiology. Therefore, we suggest that a putative cross‐talk between cannabinoids and CCK might exist and will be relevant to better understanding of physiology and pharmacology of the cannabinoid system.
Expression, distribution and ultrastructural localization of the synapse‐organizing molecule agrin in the mature avian retina
Authors: Koulen Peter , Honig Lawrence S. , Fletcher Erica L. , Kröger Stephan 
Published: March 2003

AbstractAt the vertebrate neuromuscular junction the extracellular matrix molecule agrin is responsible for the formation, maintenance and regeneration of most if not all postsynaptic specializations. Several agrin isoforms are generated by alternative splicing which differ in their function and which are all expressed in the CNS. To analyse the role of agrin in the CNS, we investigated the expression and ultrastructural localization of agrin in the posthatched chick retina. In situ hybridization revealed the presence of agrin mRNA in all cellular layers of the mature retina, indicating that most if not all major retinal cell types synthesize agrin. Pan‐specific as well as isoform‐specific antiagrin antisera stained the optic fibre layer and the outer plexiform layer. However, only the pan‐specific antiserum additionally stained the inner limiting membrane. Immunoelectron microscopy showed that in the optic fibre layer agrin was associated with ganglion cell axons and that at least part of this agrin corresponds to a neuronal isoform of agrin. In the outer plexiform layer, agrin was localized in the cleft between the photoreceptor terminals and the invaginating horizontal and bipolar cell dendrites. In the synapse‐containing inner plexiform layer both antisera revealed punctate immunoreactivity. This staining corresponded to agrin concentrated in the synaptic cleft of conventional synapses as determined by preembedding immunoelectron microscopy. Agrin is thus concentrated at mature interneuronal synapses as it is at the neuromuscular junction, consistent with a role of agrin during formation and/or maintenance of synapses in the CNS.
Comparison of the Ca2 +  currents induced by expression of three cloned α1 subunits, α1G, α1H and α1I, of low‐voltage‐activated T‐type Ca2 +  channels
Authors: Klöckner Udo , Lee Jung‐Ha , Cribbs Leanne L. , Daud Asif , Hescheler Jürgen , Pereverzev Alexei , Perez‐Reyes Edward , Schneider Toni 
Published: March 2003

AbstractExpression of rat α1G, human α1H and rat α1I subunits of voltage‐activated Ca2 +  channels in HEK‐293 cells yields robust Ca2 +  inward currents with 1.25 mm Ca2 +  as the charge carrier. Both similarities and marked differences are found between their biophysical properties. Currents induced by expression of α1G show the fastest activation and inactivation kinetics. The α1H and α1I currents activate and inactivate up to 1.5‐ and 5‐fold slower, respectively. No differences in the voltage dependence of steady state inactivation are detected. Currents induced by expression of α1G and α1H deactivate with time constants of up to 6 ms at a test potential of − 80 mV, but currents induced by α1I deactivate about three‐fold faster. Recovery from short‐term inactivation is more than three‐fold slower for currents induced by α1H and α1I in comparison to α1G. In contrast to these characteristics, reactivation after long‐term inactivation was fastest for currents arising from expression of α1I and slowest in cells expressing α1H calcium channels. The calcium inward current induced by expression of α1I is increased by positive prepulses while currents induced by α1H and α1G show little ( <  5%) or no facilitation. The data thus provide a characteristic fingerprint of each channel's activity, which may allow correlation of the α1G, α1H and α1I induced currents with their in vivo counterparts.
Apoptosis in Ca2 +  reperfusion injury of cultured astrocytes: roles of reactive oxygen species and NF‐κB activation
Authors: Takuma Kazuhiro , Lee Eibai , Kidawara Miyuki , Mori Koichi , Kimura Yuji , Baba Akemichi , Matsuda Toshio 
Published: March 2003

AbstractWe previously reported that incubation of cultured astrocytes in Ca2 + ‐containing medium after exposure to Ca2 + ‐free medium caused Ca2 +  influx followed by delayed cell death. Here, we studied the mechanisms underlying the Ca2 + ‐mediated injury of cultured astrocytes. Our results show that Ca2 +  reperfusion injury of astrocytes appears to be mediated by apoptosis, as demonstrated by DNA fragmentation and prevention of death by caspase‐3 inhibitors. Paradoxical Ca2 +  challenge stimulated rapidly reactive oxygen species (ROS) production. Ca2 +  reperfusion injury of astrocytes was influenced by several reagents which modified ROS production. When astrocytes were exposed to hydrogen peroxide (H2O2) for 30 min and then incubated without H2O2 for 1–5 days, cell toxicity including apoptosis was observed. Ca2 +  reperfusion injury induced by Ca2 +  depletion or H2O2 exposure was blocked by the iron chelator 1,10‐phenanthroline, the NF‐κB inhibitor pyrrolidinedithiocarbamate and the calcineurin inhibitor FK506. Incubation in normal medium after H2O2 exposure rapidly increased the level of nuclear NF‐κB p65 subunit, and the effect was blocked by 1,10‐phenanthroline, pyrrolidinedithiocarbamate and FK506. These findings indicate that Ca2 +  reperfusion‐induced apoptosis is mediated at least partly by ROS production and ROS cause NF‐κB activation in cultured astrocytes.
Characterization of AMPA receptors on isolated amacrine‐like cells in carp retina
Authors: Shen Ying , Zhou Yu , Yang Xiong‐Li 
Published: March 2003

AbstractIn amacrine‐like cells freshly dissociated from crucian carp (Carassius auratus) retina, we recorded whole‐cell responses to rapid application of glutamate and kainate. Currents induced by glutamate, but not kainate, usually showed extremely rapid desensitization, and the mean time constant for the decay of the responses to 10 mm glutamate was 2.77 ms. N‐methyl‐d‐aspartate (NMDA) failed to induce any current even with coapplication of glycine and removal of extracellular Mg2 + · 1‐(4‐aminophenyl)‐3‐Methylcarbamyl‐4‐methyl‐7,8‐methylenedioxy‐3,4‐dihydro‐5H‐2,3‐benzodiazepine (GYKI 53655), a selective α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptor antagonist, was found to completely block glutamate‐induced currents, suggesting that the glutamate receptors on these cells are AMPA preferring. The value of EC50 for glutamate and kainate was determined to be 2.73 mm and 97.5 μm, respectively. Noise analysis of fluctuation of whole‐cell currents induced by kainate of different concentrations indicated that the mean conductance of the AMPA receptor channels was 5.70 pS. Splice variant analysis of the AMPA receptors was also conducted by comparing the effects of cyclothiazide, a flip receptor‐preferring modulator and 4‐[2‐(phenylsulphonylamino)ethylthio]‐2,6‐difluoro‐phenoxyacetamide (PEPA), a flop receptor‐preferring modulator, on glutamate‐induced responses. PEPA was much more potent than cyclothiazide at these receptors with a EC50 of 17.3 μm. The mean ratio of the potentiation by PEPA versus cyclothiazide (P/C ratio) was 4.39. These modulatory effects of cyclothiazide and PEPA were rather similar to those obtained at AMPA receptors assembled from flop variants expressed in Xenopus oocytes, suggesting that the AMPA receptor of the carp amacrine cells may predominantly consist of the flop splice variants.
Morphological, immunophenotypical and electrophysiological properties of resting microglia in vitro
Authors: Eder Claudia , Schilling Tom , Heinemann Uwe , Haas Dorit , Hailer Nils , Nitsch Robert 
Published: March 2003

AbstractMorphological, immunophenotypical and electrophysiological properties were investigated in isolated cultured murine microglia before and after exposure to astrocyte‐conditioned medium (ACM). Following application of ACM, microglial cells underwent a dramatic shape transformation from an amoeboid appearance to a ramified morphology. In parallel to morphological changes, a downregulation of macrophage surface antigens was observed in microglia exposed to ACM. Staining intensities for major histocompatibility complex (MHC) class II molecules and for the adhesion molecules leukocyte function‐associated antigen‐1 (LFA‐1) and intercellular adhesion molecule‐1 (ICAM‐1) were significantly decreased in ramified microglia 5 days after exposure to ACM. In microglial cells treated daily with ACM over a period of 5 days, the smallest staining intensities for all surface antigens as well as the smallest ramification index as a measure for the highest degree of ramification were determined. In addition, upregulation of delayed rectifier K +  currents was observed in microglia exposed to ACM for 1 day or treated daily with ACM for 5 days. In contrast, untreated amoeboid microglia or ramified microglia analysed 5 days after exposure to ACM did not express delayed rectifier K +  currents. Analyses of the resting membrane potential and expression levels and properties of inward rectifier K +  currents did not reveal any differences between untreated and ACM‐treated microglia. It is suggested that electrophysiological properties of microglia do not strongly correlate with the morphology or the immunophenotype of microglial cells.