bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sindbis viral‐mediated expression of Ca2+‐permeable AMPA receptors at hippocampal CA1 synapses and induction of NMDA receptor‐independent long‐term potentiation
Authors: Okada Takashi , Yamada Nobuaki , Kakegawa Wataru , Tsuzuki Keisuke , Kawamura Meiko , Nawa Hiroyuki , Iino Masae , Ozawa Seiji 
Published: March 2003

AbstractGene manipulation in order to artificially express a particular gene in neurons in the central nervous system is a powerful tool for the analysis of brain function. Sindbis viral vectors have been developed to express high levels of foreign genes in postmitotic brain neurons with little transfection of glial cells. In this study, we expressed the gene encoding the unedited GluR2 (GluR‐B) subunit of the AMPA‐type glutamate receptor that forms inwardly rectifying and Ca2+‐permeable channels, in rat CA1 hippocampal neurons in slice cultures using Sindbis viral vectors. The pyramidal cell layer of the CA1 region was injected with recombinant Sindbis viruses encoding both enhanced green fluorescent protein (GFP) and unedited GluR2. The GFP fluorescence from CA1 neurons could be detected as early as 6 h and reached a maximal level about 48 h postinfection. The inwardly rectifying and Ca2+‐permeable AMPA receptors were expressed in most CA1 pyramidal cells expressing GFP. These AMPA receptors expressed by gene transfer were involved in fast excitatory neurotransmission elicited by electrical stimulation of the Schaffer collaterals in the stratum radiatum. Tetanic stimulation of Schaffer collaterals induced NMDA receptor‐independent, long‐term potentiation due to Ca2+ influx through the newly expressed AMPA receptors in the area densely stained with GFP. Thus, the combined use of Sindbis viral vectors with the GFP reporter allowed physiological examination of the roles of a specific gene product in synaptic function in well‐characterized brain neurons.
Modifications of intracellular Ca2+ signalling during nerve growth factor‐induced neuronal differentiation of rat adrenal chromaffin cells
Authors: Jiménez Nicolás , Hernández‐Cruz Arturo 
Published: March 2003

AbstractPostnatal sympathetic neurons (SNs) and chromaffin cells (CCs) derive from neural crest precursors. CCs can differentiate in vitro into SN‐like cells after nerve growth factor (NGF) exposure. This study examines changes of intracellular Ca2+ homeostasis and dynamics of CCs under conditions that promote a neuronal phenotype. Spontaneous Ca2+ fluctuations, a frequent observation in early cultures of CCs, diminished after > 10 days in vitro in control cells and ceased in NGF‐treated ones. At the same time, Ca2+ rises resulting from entry upon membrane depolarization, gradually increased both their size and peak d[Ca2+]i/dt, resembling those recorded in SNs. Concomitantly, caffeine‐induced Ca2+ rises, resulting from Ca2+ release from intracellular stores, increased their size and their peak d[Ca2+]i/dt by > 1000%, and developed transient and sustained release components, similar to those of SNs. The transient component, linked to regenerative Ca2+ release, appeared after > 10 days of NGF treatment, suggesting a delayed steep enhancement of Ca2+‐induced Ca2+ release (CICR). Immunostaining showed that proteins coded by the three known isoforms of ryanodine receptors (RyRs) are present in CCs, but that only RyR2 increased significantly after NGF treatment. Since the transient release component increased more steeply than RyR2 immunostaining, we suggest that the development of robust CICR requires both an increased expression of RyRs and more efficient functional coupling among them. NGF‐induced transdifferentiation of chromaffin cells involves the enhancement of both voltage‐gated Ca2+ influx and Ca2+ release from intracellular stores. These modifications are likely to complement the extensive morphological and functional reorganization required for the replacement of the endocrine phenotype with the neuronal one.
Protein kinase Cα and β1 isoforms are regulators of α‐secretory proteolytic processing of amyloid precursor protein in vivo
Authors: Roßner S. , Mendla K. , Schliebs R. , Bigl V. 
Published: March 2003

AbstractWe have recently shown that in utero treatment of guinea pigs with the DNA methylating substance methylazoxymethanol acetate (MAM) results in neocortical microencephalopathy, increased protein kinase C (PKC) activity and altered processing of the amyloid precursor protein (APP) in neocortex of offspring. Here we show that PKCα and PKCβ1 are the key regulators of α‐secretory APP processing in guinea pig neocortex under these experimental conditions in vivo. This conclusion is based on the selective translocation of PKCα and PKCβ1 isoforms to the cell membrane in MAM‐treated guinea pigs, as revealed by Western blot analysis and by immunocytochemistry. Additionally, we observed that [3H]phorbol ester binding to protein kinase C increased by 38% and enhanced basal PKC activity by 58% in the neocortex of microencephalic guinea pigs. Inhibition of PKCα/PKCβ1 by Gö6976 abolished this difference, suggesting that constitutive overactivation of these PKC isoforms accounts for the increase in total PKC activity. We also observed a strong positive correlation between levels of α‐secretase‐processed APP and PKC activity in the neocortex of individual animals, providing further evidence for a significant role of classical PKC isoforms in nonamyloidogenic APP processing.
Nitric oxide up‐regulates ferritin mRNA level in snail neurons
Authors: Xie Mingqiang , Hermann Anton , Richter Klaus , Engel Edwin , Kerschbaum Hubert H. 
Published: March 2003

AbstractWe cloned and sequenced the ferric ion‐binding protein, ferritin, from the nervous system of the pulmonate snail, Helix pomatia. Helix H‐ferritin cDNA contains a 519‐bp open reading frame (ORF) and predicts an iron‐responsive element (IRE) at the 5′‐untranslated region (5′‐UTR) of the ferritin mRNA. The deduced amino acid sequence revealed 86% similarity with Lymnaea stagnalis ferritin and about 70% similarity with vertebrate H‐ferritin. While secreted ferritin isoforms contain a signalling sequence at their N‐terminal end, Helix ferritin does not contain this sorting signal indicating that it is restricted to the cytoplasm. The amino acid ligands at positions Glu25, Tyr30, Glu59, Glu60, His63, Glu105 and Gln139 indicate an active ferroxidase site in Helix ferritin. In situ hybridization visualized ferritin mRNA in neuronal cell bodies but not in the neuropil. In contrast, ferritin‐immunoreactive protein was localized in cell bodies and neurites. We further demonstrate that the NO donors S‐nitroso‐N‐acetylpenicillamine (SNAP), or hydroxylamine (HA), increase the intracellular ferritin mRNA level by about 55%. In conclusion, our findings show that Helix neurons express an intracellular H‐ferritin isoform and suggest that iron and NO metabolism are coupled.
Neural correlates of religious experience
Authors: Azari Nina P. , Nickel Janpeter , Wunderlich Gilbert , Niedeggen Michael , Hefter Harald , Tellmann Lutz , Herzog Hans , Stoerig Petra , Birnbacher Dieter , Seitz Rüdiger J. 
Published: March 2003

AbstractThe commonsense view of religious experience is that it is a preconceptual, immediate affective event. Work in philosophy and psychology, however, suggest that religious experience is an attributional cognitive phenomenon. Here the neural correlates of a religious experience are investigated using functional neuroimaging. During religious recitation, self‐identified religious subjects activated a frontal–parietal circuit, composed of the dorsolateral prefrontal, dorsomedial frontal and medial parietal cortex. Prior studies indicate that these areas play a profound role in sustaining reflexive evaluation of thought. Thus, religious experience may be a cognitive process which, nonetheless, feels immediate.
Multiple‐site optical recording reveals embryonic organization of synaptic networks in the chick spinal cord
Authors: Mochida Hiraku , Sato Katsushige , Arai Yoshiyasu , Sasaki Shinichi , Yazawa Itaru , Kamino Kohtaro , Momose‐Sato Yoko 
Published: March 2003

AbstractWe examined embryonic expression of postsynaptic potentials in stages 26–31 (E5 to E7) chick spinal cord slices. Slow optical signals related to the postsynaptic potentials which were evoked by electrical stimulation of afferent fibers were identified in the dorsal grey matter and the ventral motoneuronal area. In cervical spinal cord (C13) preparations, the dorsal slow signal appeared from stage 28 (E6), whilst the ventral slow signal was recognized from stage 29. At stages 26 and 27 (E5), no slow signal was observed in either the dorsal or ventral regions. On the other hand, in lumbosacral spinal cord (LS5) preparations, the dorsal, as well as ventral, slow signals appeared from stage 29; at stage 28 no slow signal was detected in the dorsal or ventral regions. These results suggest that there are differences in the ontogenetic expression of synaptic functions between the dorsal and ventral regions, and between the cervical and lumbosacral spinal cords. In embryos older than stage 29, removal of Mg2+ from the bathing solution markedly enhanced the amplitude and incidence of the ventral slow signal. In addition, in C13 preparations at stage 28, removal of Mg2+ elicited small slow signals in the ventral region in which no synaptic response was evoked in normal Ringer's solution. The slow signals induced in the Mg2+‐free solution were blocked by 2‐amino‐5‐phosphonovaleric acid (APV), showing that they are attributable to N‐methyl‐d‐aspartate (NMDA) receptors. These results suggest that functional synaptic connections via polysynaptic pathways are already generated on motoneurons, but are suppressed by a Mg2+ block on the NMDA receptors at developmental stages when synaptic transmission from the primary afferents to the dorsal interneurons is initially expressed in the dorsal region.
Regulation of SSAT expression by synaptic activity
Authors: Ingi Tatsuya , Worley Paul F. , Lanahan Anthony A. 
Published: March 2003

AbstractNeuronal activity is a requirement for the plasticity and normal development of the central nervous system. We have used differential cloning techniques to identify an immediate‐early gene (IEG) that is rapidly induced in neurons by activity in both adult and developmental models of plasticity. Here we describe the key regulatory enzyme of polyamine catabolism, spermidine/spermine N1‐acetyltransferase (SSAT), as a neuronal IEG. In the rat brain, kainate‐induced seizures result in a 5.5‐fold increase in the amount of SSAT mRNA above basal levels and the enzymatic activity is increased twofold. Expression of SSAT mRNA is rapidly and transiently upregulated in the cerebral cortex and hippocampus by seizure‐induced neuronal activation. In hippocampal neurons, SSAT expression is dynamically responsive to synaptic activity in the long‐term potentiation (LTP) paradigm. In developing brain, region‐specific expression of SSAT mRNA is first detected at postnatal day 9 (P9) and subsequently increases through days P15, P20, before reaching maximal level in adult animals. This dynamic transcriptional and translational control suggests that SSAT may play a role in activity‐dependent neuronal plasticity and development.
Novelty enhances retrieval: molecular mechanisms involved in rat hippocampus
Authors: Izquierdo L. A. , Viola H. , Barros D. M. , Alonso M. , Vianna M. R. M. , Furman M. , Levi de Stein M. , Szapiro G. , Rodrigues C. , Choi H. , Medina J. H. , Izquierdo I. 
Published: March 2003

AbstractRats exposed to a novel environment just prior to or 1–2 h, but not 4 or 6 h, before retention testing exhibited an enhanced retrieval of a one‐trial inhibitory avoidance training. The bilateral intrahippocampal infusion of PD098059, an inhibitor of mitogen‐activated protein kinase (MAPK), the specific upstream activator of p42 and p44 MAPKs, given 10 min before the exposure to the novel environment, blocked the enhancing effect of novelty on memory retrieval. In addition, prenovelty infusion of dl‐2‐amino‐5‐phosphonovalerate (APV), an antagonist of glutamate NMDA receptors, produced similar effects. The exposure to the novel environment is associated with an activation of p42 and p44 MAPKs and an increase in the phosphorylation state of the transcription factor cAMP response element binding protein (CREB). No changes were observed in cAMP‐dependent protein kinase (PKA) activity or in α‐CAMKII activation. Taken together, our results indicate that novelty activates hippocampal MAPKs, which are necessary, along with glutamate NMDA receptors, for the enhancing effect of novelty on retrieval.
Fear memory retrieval induces CREB phosphorylation and Fos expression within the amygdala
Authors: Hall Jeremy , Thomas Kerrie L. , Everitt Barry J. 
Published: March 2003

AbstractFear memory retrieval has been shown to induce a protein‐synthesis dependent re‐consolidation of memories within the amygdala. Here, using immunocytochemistry, we investigated the molecular basis of this process in the rat and show that retrieval of a cued fear memory induces the activation, by phosphorylation, of the transcription factor CREB within the basal and lateral nuclei of the amygdala, as well as expression of the CREB‐regulated immediate‐early gene, c‐fos, in the basal amygdala. We also show an increase in CREB phosphorylation within the central nucleus of the amygdala following behavioural testing, with an accompanying increase in Fos‐immunoreactive nuclei in animals retrieving the cued association. There were no changes in either phosphorylated CREB or Fos in the hippocampus following exposure to discrete fear stimuli. These results show that activation of CREB, which has been shown to be involved in the formation of long‐term fear memories, also accompanies memory retrieval, and also suggest a role for CREB phosphorylation in memory re‐consolidation following retrieval.
Kindling of claustrum and insular cortex: comparison to perirhinal cortex in the rat
Authors: Mohapel Paul , Zhang Xia , Gillespie Greg W. , Chlan‐Fourney Jennifer , Hannesson Darren K. , Corley Shannon M. , Li Xin‐Min , Corcoran Michael E. 
Published: March 2003

AbstractThe perirhinal cortex has recently been implicated in the kindling of limbic generalized seizures. The following experiments in rats tested the selectivity of the perirhinal cortex's epileptogenic properties by comparing its kindling profile with those of the adjacent insular cortex, posterior (dorsolateral) claustrum and amygdala. The first experiment examined the kindling and EEG profiles, and found that both the claustrum and insular cortex demonstrated rapid epileptogenic properties similar to the perirhinal cortex, including very rapid kindling rates and short latencies to convulsion. Furthermore, electrical stimulation of all three structures led to a two‐phase progression through stage‐5 seizures which had characteristics of both neocortical and amygdaloid kindling. In a second experiment rats were suspended in a harness to allow for more detailed documentation of both forelimb and hindlimb convulsions. With this procedure we were able to detect subtle yet unique differences in convulsion characteristics from each of the kindled sites and stage‐5 seizure phases. Some of these convulsive parameters were correlated with changes in FosB/ΔFosB protein and BDNF mRNA expression measured two hours after the last convulsion. Overall, it appears that the perirhinal cortex is not unique in its property of rapid epileptogenesis. Moreover, the posterior claustrum exhibited the fastest kindling and most vigorous patterns of clonus, suggesting that it may be even more intimately associated with the motor substrates responsible for limbic seizure generalization than is the perirhinal cortex.
For whales and seals the ocean is not blue: a visual pigment loss in marine mammals*
Authors: Peichl Leo , Behrmann Günther , Kröger Ronald H. H. 
Published: March 2003

AbstractMost terrestrial mammals have colour vision based on two spectrally different visual pigments located in two types of retinal cone photoreceptors, i.e. they are cone dichromats with long‐to‐middle‐wave‐sensitive (commonly green) L‐cones and short‐wave‐sensitive (commonly blue) S‐cones. With visual pigment‐specific antibodies, we here demonstrate an absence of S‐cones in the retinae of all whales and seals studied. The sample includes seven species of toothed whales (Odontoceti) and five species of marine carnivores (eared and earless seals). These marine mammals have only L‐cones (cone monochromacy) and hence are essentially colour‐blind. For comparison, the study also includes the wolf, ferret and European river otter (Carnivora) as well as the mouflon and pygmy hippopotamus (Artiodactyla), close terrestrial relatives of the seals and whales, respectively. These have a normal complement of S‐cones and L‐cones. The S‐cone loss in marine species from two distant mammalian orders strongly argues for convergent evolution and an adaptive advantage of that trait in the marine visual environment. To us this suggests that the S‐cones may have been lost in all whales and seals. However, as the spectral composition of light in clear ocean waters is increasingly blue‐shifted with depth, an S‐cone loss would seem particularly disadvantageous. We discuss some hypotheses to explain this paradox.
Delayed infusion of GDNF promotes recovery of motor function in the partial lesion model of Parkinson's disease
Authors: Kirik Deniz , Georgievska Biljana , Rosenblad Carl , Björklund Anders 
Published: March 2003

AbstractHere we studied the effects of glial cell line‐derived neurotrophic factor (GDNF) in a rat model that represents the symptomatic stages of Parkinson's disease. GDNF was infused starting 2 weeks after an intrastriatal 6‐hydroxydopamine (6‐OHDA) lesion in order to halt the ongoing degeneration of the nigrostriatal dopaminergic neurons. GDNF or vehicle was infused in the striatum or the lateral ventricle via an osmotic minipump over a total 4‐week period (2–6 weeks postlesion). Motor function was evaluated by the stepping, paw reaching and drug‐induced motor asymmetry tests before the pump infusion was initiated, and was repeated once during (5 weeks postlesion) and twice after the withdrawal of the minipumps (7 and 11 weeks postlesion). We found that within two weeks following the lesion ≈ 40% of the nigral TH‐positive neurons were lost. In the vehicle infusion groups there was an additional 20% cell loss between 2 and 12 weeks after the lesion. This latter cell loss occurred mainly in the caudal part of the SN whereas the cell loss in the rostral SN was almost complete within the first two weeks. Ventricular GDNF infusion completely blocked the late degenerating neurons in the caudal SN and had long lasting behavioural effects on the stepping test and amphetamine rotation, extending to 6 weeks after withdrawal of the factor. Striatal infusion affected the motor behaviour transiently during the infusion period but the motor performance of these animals returned to baseline upon cessation of the GDNF delivery, and the delayed nigral cell loss was marginally affected. We conclude that intraventricular GDNF can successfully block the already initiated degenerative process in the substantia nigra, and that the effects achieved via the striatal route, when GDNF is given acutely after the lesion, diminish as the fibre terminal degeneration proceeds.
Behavioural profiling of a murine Charcot–Marie–Tooth disease type 1A model
Authors: Norreel J. C. , Jamon M. , Riviere G. , Passage E. , Fontes M. , Clarac F. 
Published: March 2003

AbstractDifferent features of motor behaviour were studied on a transgenic mouse model of Charcot–Marie–Tooth's disease (CMT). Mutants with 4 or 7 copies of the human PMP22 gene leading to a phenotype significantly close to CMT's disease type 1A were compared with control animals. The aim of the study was to validate this transgenic model and to characterise the impairments occurring in the various lines. Three main types of analysis were performed in 2‐month‐old mice without any peculiar visible deficit: (i) a study of standardised clinical tests (SHIRPA protocol) demonstrated that only a few motor deficits were expressed; (ii) a measurement of general spontaneous activity by means of a commercial video‐tracking system was performed and revealed that the main spontaneous activities were identical in the three lines with, however, some slight localised modifications; and, (iii) by contrast, the three lines respond very differently to the footprints, grip strength, splay test and rotarod test. Even in lines with a significantly limited copy number of the transgene, we observed and quantified impairments. In conclusion, mutants of CMT1A seem to be a very pertinent model of this human pathology and will certainly be useful for therapeutic procedures and for theoretical studies on this disease.
Cannabinoid receptor activation and elevated cyclic AMP reduce glutamate neurotoxicity
Authors: Hampson A. J. , Grimaldi M. 
Published: March 2003

AbstractCannabinoid receptor activation in vivo reduces ischemic injury, a phenomenon that has not been successfully reproduced in vitro. Because cyclic adenosine monophosphate (cAMP) levels are radically elevated during ischemic reperfusion, but cannabinoid receptor activation reduces cAMP levels, we hypothesized that cannabinoids might prevent in vitro glutamate toxicity if reperfusion was simulated by cAMP supplementation after glutamate removal. Although neuronal cultures were unaffected by the single addition of either cannabinoid or dibutyryl cAMP (dbcAMP), glutamate toxicity was reduced by 20% when cannabinoid was present during glutamate exposure and either dbcAMP or forskolin was added after glutamate removal. Further studies revealed that cannabinoid receptor activation reduces glutamate toxicity by attenuating calcium influx through N‐ and P/Q‐type calcium channels. The effect of glutamate exposure on neuronal cAMP levels was also examined. Glutamate exposure significantly reduced neuronal cAMP levels, although suppression was even greater when cannabinoid was present. Because neurological outcome after ischemia is poor when cAMP levels during reperfusion are low, it is hypothesized that cAMP elevation after glutamate exposure may offset excitotoxic and/or cannabinoid receptor‐induced cAMP depletion. Cannabinoids protect against ischemic injury in vivo, but only reduce toxicity in vitro when cAMP levels are elevated, possibly suggesting that cAMP elevation during reperfusion reduces brain injury by off‐setting the effect of Gi/o protein‐coupled systems on adenylate cyclase.