bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation and activation of the Nrf‐1 transcription factor in the lesioned hippocampus
Authors: Hertel Moritz , Braun Susanne , Durka Silke , Alzheimer Christian , Werner Sabine 
Published: March 2003

AbstractThe Nrf‐1 and Nrf‐2 transcription factors play a pivotal role in the cellular defence against the toxic effects of reactive oxygen species (ROS). Although ROS are key effectors of neuronal death after ischaemic and traumatic brain injury, it is not known whether Nrf‐1 and Nrf‐2 are involved in neuroprotective signalling. Here, we analysed the temporal and spatial expression pattern of Nrf‐1 and Nrf‐2 after unilateral excitotoxic lesion of mouse hippocampus. In marked contrast to previous in vitro studies, where upregulation of these transcription factors on the mRNA level was never detected, we found a strong induction of Nrf‐1 mRNA and protein expression in neurons of the lesioned hippocampus, accompanied by a weak elevation of Nrf‐2 mRNA levels. Nrf‐1 predominantly localized to the nucleus in the injured hippocampus. Furthermore, expression of the cytoprotective enzyme, heme oxygenase‐1, a major target of Nrf‐1 and Nrf‐2 action, was coregulated with Nrf‐1 in the same hippocampal neurons, suggesting that Nrf‐1 is functionally active. Because Nrf‐1 and Nrf‐2 are potent inducers of various cytoprotective proteins, our data suggest a role of Nrf‐1 and Nrf‐2 in neuronal survival after acute brain injury.
Laterality of the pontocerebellar projections in the rat
Authors: Serapide M. F. , Zappalà A. , Parenti R. , Pantò M. R. , Cicirata F. 
Published: March 2003

AbstractThis study aimed to investigate the trajectory of fibres from the pontine nuclei that reach the two sides of the cerebellum. Injections of biotinylated dextran amine (BDA) were made within the basilar pontine nuclei (BPN) and the nucleus reticularis tegmenti pontis (NRTP) in one side of rats with electrolytic injury of the middle cerebellar peduncle (MCP), ipsilateral or contralateral to the side of injection. Fibres were traced from the pontine nuclei (BPN and NRTP) to both sides of the cerebellum passing through the respective MCPs. The study carried out in rats with injury to one peduncle showed projections segregated to the half‐side of the cerebellum innervated by the intact peduncle. The laterality observed was confirmed by a retrograde tracer study. In fact, injections of different fluorescent tracers in rats with injury of single MCP showed that in the pontine nuclei only cell bodies stained by the tracer injected in the half‐cerebellum ipsilateral to the intact peduncle. Finally, similar injections (i.e. different fluorescent tracers in symmetric areas of the cerebellar cortex) in the cerebellum of intact brain rats showed that BPN and NRTP differ for the laterality of their projections. In fact, 82% of BPN cells project contralaterally and 18% ipsilaterally, whereas 60% of NRTP cells project contralaterally and 40% ipsilaterally. In conclusion, this study showed that the MCPs receive fibres from the pontine nuclei of both sides and project to the ipsilateral half of the cerebellum and that different contingents of projections to the two sides of the cerebellum arise from BPN and NRTP.
Mapping the oculomotor system: the power of transneuronal labelling with rabies virus
Authors: Graf Werner , Gerrits Nicolaas , Yatim‐Dhiba Najiya , Ugolini Gabriella 
Published: March 2003

AbstractNeuronal networks underlying and related to horizontal eye movements were visualized by retrograde transneuronal tracing with rabies virus from the left medial rectus muscle in guinea pigs. Time‐sequenced labelling revealed distinct circuitries involved in particular oculomotor functions, i.e. vestibulo‐ocular reflex and saccade generation (brainstem circuitry), adaptive plasticity (cerebellar modules) and possibly motivation and navigation (limbic, hippocampal and cortical structures). Our results provide a first comprehensive road map of the oculomotor system that is unsurpassed by any previous tracing study. We report a number of unexpected findings that illustrate a much vaster and more complicated network for the control of the relatively simple horizontal eye movements than had been envisioned previously.
Cell‐specific expression of the glutamine transporter SN1 suggests differences in dependence on the glutamine cycle
Authors: Boulland Jean‐Luc , Osen Kirsten K. , Levy Line M. , Danbolt Niels Christian , Edwards Robert H. , Storm‐Mathisen Jon , Chaudhry Farrukh A. 
Published: March 2003

AbstractGlutamine is involved in a variety of metabolic processes, including recycling of the neurotransmitters glutamate and γ‐aminobutyric acid (GABA). The system N transporter SN1 mediates efflux as well as influx of glutamine in glial cells [Chaudhry et al. (1999), Cell, 99, 769–780]. We here report qualitative and quantitative data on SN1 protein expression in rat. The total tissue concentrations of SN1 in brain and in kidney are half and one‐quarter, respectively, of that in liver, but the average concentration of SN1 could be higher in astrocytes than in hepatocytes. Light and electron microscopic immunocytochemistry shows that glutamatergic, GABAergic and, surprisingly, purely glycinergic boutons are ensheathed by astrocytic SN1 laden processes, indicating a role of glutamine in the production of all three rapid transmitters. A dedication of SN1 to neurotransmitter recycling is further supported by the lack of SN1 immunoreactivity in oligodendrocytes (cells rich in glutamine but without perisynaptic processes). All neuronal structures appear unlabelled implying that a different protein mediates glutamine uptake into nerve endings. In several regions, SN1 immunoreactivity is higher in association with GABAergic than glutamatergic synapses, in agreement with observations that exogenous glutamine increases output of transmitter glutamate but not GABA. Nerve terminals with low transmitter reuptake or high prevailing firing frequency are associated with high SN1 immunoreactivity in adjacent glia. Bergmann glia and certain other astroglia contain very low levels of SN1 immunoreactivity compared to most astroglia, including retinal Müller cells, indicating the possible existence of SN isoforms and alternative mechanisms for transmitter recycling.
Activity‐dependent receptive field changes in the surround of adult cat visual cortex lesions
Authors: Schweigart Georg , Eysel Ulf T. 
Published: March 2003

AbstractExtracellular single cell spike activity was recorded in the visual cortex of anaesthetized adult cats at identical sites before and 2 days after focal excitotoxic lesions induced by injections of ibotenic acid. In the surround of the lesions (up to 5 mm from the border of the lesion), the average postlesion receptive field (RF) sizes were not different from the prelesion RFs. However, RFs of neurons with increased postlesion excitability were slightly enlarged; such neurons were mainly found close to the anterior border of the lesion (≤ 1 mm). After applying a visual training procedure for 1 h to the postlesion RFs (repetitive, synchronous stimulation of a part of the RF and the neighbouring unresponsive part of the visual field), there was a small (0.4–0.8°) but significant and specific increase of RF size in about half of the tested neurons. This RF enlargement was similar to that observed with the same training procedure in the visual cortex of normal cats. Thus, small RF changes can be induced by visual stimulation within one hour in normal cells as well as in cells at the border of cortical lesions. Any differences between normal and lesioned animals appear to be related to lesion‐induced changes of excitability.
Analysis of the function of GABAB receptors on inhibitory afferent neurons of Purkinje cells in the cerebellar cortex of the rat
Authors: Than Marta , Szabo Bela 
Published: March 2003

AbstractPurkinje cells, the output neurons of the cerebellar cortex, receive inhibitory input from basket, stellate and neighbouring Purkinje cells. The aim of the present study was to clarify the role of GABAB receptors on neurons giving inhibitory input to Purkinje cells. In sagittal slices prepared from the cerebellar vermis of the rat, the GABAB receptor agonist baclofen lowered the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) recorded in Purkinje cells. These effects were prevented by the GABAB receptor antagonist CGP 55845. Two mechanisms were involved in the depression of the inhibitory input to Purkinje cells. The first mechanism was suppression of the firing of basket, stellate and Purkinje cells. The second mechanism was presynaptic inhibition of GABA release from terminals of the afferent axons. This was indicated by the finding that baclofen decreased the amplitude of IPSCs occurring in Purkinje cells synchronously with action potentials recorded in basket cells. A further support for the presynaptic inhibition is the observation that baclofen decreased the amplitude of autoreceptor currents which are due to activation of GABAA autoreceptors at axon terminals of basket cells by synaptically released GABA. The presynaptic inhibition was partly due to direct inhibition of the vesicular release mechanism, because baclofen lowered the frequency of miniature IPSCs recorded in Purkinje cells in the presence of cadmium and in the presence of tetrodotoxin plus ionomycin. The results show that activation of GABAB receptors decreased GABAA receptor‐mediated synaptic input to cerebellar Purkinje cells both by lowering the firing rate of the inhibitory input neurons and by inhibiting GABA release from their axon terminals with a presynaptic mechanism.
Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70
Authors: Rubio Eva , Valenciano Ana I. , Segundo Carmen , Sánchez Noelia , De Pablo Flora , De La Rosa Enrique J. 
Published: March 2003

AbstractNeuronal cell death is a genuine developmental process, with precise regulation and defined roles. In striking contrast, characterization of cell death that occurs at early stages of neural development is very limited. We previously showed that embryonic proinsulin increases the level of the chaperone heat shock cognate 70 (Hsc70) and reduces the incidence of apoptosis in the neurulating chick embryo [de la Rosa, et al. (1998), Proc. Natl. Acad. Sci. USA, 95, 9950]. We now demonstrate that Hsc70 is directly involved in cell survival during neurulation, as specific downregulation of endogenous Hsc70 by antisense oligodeoxynucleotide interference provoked an increase in apoptosis both in vitro and in ovo. In parallel, activation of caspase‐3 was increased after hsc70 antisense oligodeoxynucleotide treatment. Dead cells were located mostly in the developing nervous system, distributed in areas where the incidence of cell death was high. These areas coincided both in vivo and under different death‐inducing conditions, including antisense interference and growth factor deprivation. Hsc70 immunostaining was strong in at least some areas of high cell death. Apoptotic cells within these areas presented undetectable Hsc70 levels, however, suggesting that this protein acts as an intrinsic protector of neuroepithelial and neural precursor cells.
Modulation of Ca2+currents in rat thalamocortical relay neurons by activity and phosphorylation
Authors: Meuth Sven , Pape Hans‐Christian , Budde Thomas 
Published: March 2003

AbstractRhythmic low and high frequency activity in thalamocortical networks depend critically on activation of low‐ and high‐voltage‐activated (LVA, HVA) Ca2+currents. In order to test whether Ca2+currents are modified during repetitive activation, acutely isolated thalamocortical relay neurons of rats, at postnatal days 12 (P12) to P20, were investigated using patch‐clamp, Ca2+imaging and Western blot techniques. High‐voltage‐activated, but not LVA Ca2+currents were reduced significantly during 2 Hz stimulation. Ca2+imaging experiments demonstrated a close correlation between the increase in intracellular Ca2+levels and the decrease in HVA Ca2+current amplitudes. Further examination of HVA Ca2+currents revealed a ‘U‐shaped’ inactivation curve and a time‐dependent inactivation process that could be described by a two‐exponential function. The ‘U‐shape’ was significantly reduced, current amplitude was increased significantly and time‐dependent inactivation revealed a one‐exponential decline with Ba2+as the charge carrier, following activation of the cAMP/PKA pathway, and following application of phosphatase inhibitors (ascomycin, calyculin A). Western blot analysis and the effect of ascomycin indicated an involvement of calcineurin in the inactivation process. Isolation of HVA Ca2+current components by subtype‐specific blockers revealed that changes in time‐dependent inactivation, inactivation curve and current amplitude were carried mainly by L‐type and N‐type Ca2+currents. Furthermore, Ca2+‐dependent inactivation was operative during stimulation protocols mimicking tonic action potential firing. These data indicate a modulation of L‐ and N‐type Ca2+channels by phosphorylation, resulting jointly in an increased intracellular Ca2+influx during activity of the ascending brainstem system, the latter occurring during states of wakefulness.
Selective chronic stress‐induced in vivo ERK1/2 hyperphosphorylation in medial prefrontocortical dendrites: implications for stress‐related cortical pathology?
Authors: Trentani A. , Kuipers S. D. , Ter Horst G. J. , Den Boer J. A. 
Published: March 2003

AbstractStress has been shown to affect brain structural plasticity, promote long‐term changes in multiple neurotransmitter systems and cause neuronal atrophy. However, the mechanisms involved in these stress‐related neural alterations are still poorly understood. Mitogen‐activated protein kinase (MAPK) cascades play a crucial role in the transduction of neurotrophic signal from the cell surface to the nucleus and are implicated in the modulation of synaptic plasticity and neuronal survival. An intriguing possibility is that stress might influence brain plasticity through its effects on selective members of such intracellular signalling cascades responsible for the transduction of neurotrophin signals. Here, we have investigated the effects of stress on the expression of three members of the MAPK/extracellular‐regulated kinase (ERK) pathway such as phospho‐ERK1, phospho‐ERK2 and phospho‐cAMP/calcium‐responsive element‐binding protein (CREB) in the adult rat brain. Male rats were subjected to mild footshocks and the patterns of protein expression were analysed after 21 consecutive days of stress. We found that chronic stress induced a pronounced and persistent ERK1/2 hyperphosphorylation in dendrites of the higher prefrontocortical layers (II and III) and a reduction of phospho‐CREB expression in several cortical and subcortical regions. We hypothesized that defects in ERK signalling regulation combined with a reduced phospho‐CREB activity may be a crucial mechanism by which sustained stress may induce atrophy of selective subpopulations of vulnerable cortical neurons and/or distal dendrites. Thus, ERK‐mediated cortical abnormalities may represent a specific path by which chronic stress affects the functioning of cortical structures and causes selective neural network defects.
Creatine kinase B‐driven energy transfer in the brain is important for habituation and spatial learning behaviour, mossy fibre field size and determination of seizure susceptibility
Authors: Jost Carolina R. , Van der Zee Catharina E. E. M. , In ‘t Zandt Henricus J. A. , Oerlemans Frank , Verheij Michel , Streijger Femke , Fransen Jack , Heerschap Arend , Cools Alexander R. , Wieringa Bé 
Published: March 2003

AbstractCreatine kinases are important in maintaining cellular‐energy homeostasis, and neuroprotective effects have been attributed to the administration of creatine and creatine‐like compounds. Herein we examine whether ablation of the cytosolic brain‐type creatine kinase (B‐CK) in mice has detrimental effects on brain development, physiological integrity or task performance. Mice deficient in B‐CK (B‐CK–/–) showed no gross abnormalities in brain anatomy or mitochondrial ultrastructure, but had a larger intra‐ and infrapyramidal mossy fibre area. Nuclear magnetic resonance spectroscopy revealed that adenosine triphosphate (ATP) and phosphocreatine (PCr) levels were unaffected, but demonstrated an apparent reduction of the PCr ⇆ ATP phosphorus exchange capacity in these mice. When assessing behavioural characteristics B‐CK–/– animals showed diminished open‐field habituation. In the water maze, adult B‐CK–/– mice were slower to learn, but acquired the spatial task. This task performance deficit persisted in 24‐month‐old, aged B‐CK–/– mice, on top of the age‐related memory decline normally seen in old animals. Finally, a delayed development of pentylenetetrazole‐induced seizures (creating a high‐energy demand) was observed in B‐CK–/– mice. It is suggested that the persistent expression of the mitochondrial isoform ubiquitous mitochondrial CK (UbCKmit) in the creatine/phospho‐creatine shuttle provides compensation for the loss of B‐CK in the brain. Our studies indicate a role for the creatine–phosphocreatine/CK circuit in the formation or maintenance of hippocampal mossy fibre connections, and processes that involve habituation, spatial learning and seizure susceptibility. However, for fuelling of basic physiological activities the role of B‐CK can be compensated for by other systems in the versatile and robust metabolic‐energy network of the brain.
Metabotropic glutamate receptors mediate expression of LTP in slices of rat visual cortex
Authors: Huemmeke Markus , Eysel Ulf T. , Mittmann Thomas 
Published: March 2003

AbstractLong‐term‐potentiation (LTP) can be induced by application of a standard theta‐burst stimulation protocol in slice preparations of the neocortex. This type of LTP is known to be dependent on the activation of NMDA receptors. The present study used specific experimental conditions to evoke a non‐NMDA receptor mediated type of LTP. By use of weak theta‐burst stimulation (wTBS) we describe a non‐NMDA receptor dependent LTP in rat visual cortex in vitro, which is sensitive to an antagonist of metabotropic glutamate receptors (mGluR). In slices of the visual cortex we stimulated ascending inputs in cortical layer IV and recorded extracellular field potentials (FPs) from cortical layers II/III. In disinhibited slices (with 1 µm picrotoxin), a wTBS induced LTP to 138% of control. The expression of this potentiation was insensitive to the NMDA‐receptor antagonist, D‐AP5, but could be abolished by application of the mGluR antagonist MCPG. These data suggest an NMDA‐independent mechanism for LTP induction in the visual cortex which can be observed in layer II/III neurons.
Contralateral inhibition as a sensory bias: the neural basis for a female preference in a synchronously calling bushcricket, Mecopoda elongata
Authors: Römer Heiner , Hedwig Berthold , Ott Swidbert R. 
Published: March 2003

AbstractImperfect synchrony between male calls occurs widely in acoustically courting crickets and bushcrickets. Males which are able to establish the temporal leadership usually attract more females in choice experiments but the proximate mechanism for this precedence effect is unknown. Here we show that contralateral inhibition, the neural basis for lateral contrast enhancement in the auditory pathways of insects and vertebrates, is also the probable proximate neural mechanism for this female preference. We recorded simultaneously from a pair of identified auditory interneurons in the synchronizing bushcricket Mecopoda elongata. When two identical acoustic stimuli are presented from opposite directions, one preceding the other by 120 ms, the neural representation within the receiver is far stronger for the leader signal. This results from a suppression of the neural response to the follower chirp by reciprocal contralateral inhibition. The advantage of the representation of the leader is 2–3‐fold with time delays between 70 and 130 ms; the most clear‐cut female preferences have also been found with such delays in previous behavioural experiments. In time–intensity trading experiments, a lead by 120 ms could only be compensated for by increasing the amplitude of the follower signal by 7–11 dB. We discuss contralateral inhibition in auditory systems as a sensory bias that results in female preference for leading signals, with important evolutionary consequences for male calling strategies.
The neglected constituent of the basal forebrain corticopetal projection system: GABAergic projections
Authors: Sarter Martin , Bruno John P. 
Published: March 2003

AbstractAt least half of the basal forebrain neurons which project to the cortex are GABAergic. Whilst hypotheses about the attentional functions mediated by the cholinergic component of this corticopetal projection system have been substantiated in recent years, knowledge about the functional contributions of its GABAergic branch has remained extremely scarce. The possibility that basal forebrain GABAergic neurons that project to the cortex are selectively contacted by corticofugal projections suggests that the functions of the GABAergic branch can be conceptualized in terms of mediating executive aspects of cognitive performance, including the switching between multiple input sources and response rules. Such speculations gain preliminary support from the effects of excitotoxic lesions that preferentially, but not selectively, target the noncholinergic component of the basal forebrain corticopetal system, on performance in tasks involving demands on cognitive flexibility. Progress in understanding the cognitive functions of the basal forebrain system depends on evidence regarding its main noncholinergic components, and the generation of such evidence is contingent on the development of methods to manipulate and monitor selectively the activity of the GABAergic corticopetal projections.
Endogenous histamine in the medial septum–diagonal band complex increases the release of acetylcholine from the hippocampus: a dual‐probe microdialysis study in the freely moving rat
Authors: Bacciottini Lucia , Passani Maria Beatrice , Giovannelli Lisa , Cangioli Iacopo , Mannaioni Pier Francesco , Schunack Walter , Blandina Patrizio 
Published: March 2003

AbstractThe effects of histaminergic ligands on both ACh spontaneous release from the hippocampus and the expression of c‐fos in the medial septum–diagonal band (MSA‐DB) of freely moving rats were investigated. Because the majority of cholinergic innervation to the hippocampus is provided by MSA‐DB neurons, we used the dual‐probe microdialysis technique to apply drugs to the MSA‐DB and record the induced effects in the projection area. Perfusion of MSA‐DB with high‐KCl medium strongly stimulated hippocampal ACh release which, conversely, was significantly reduced by intra‐MSA‐DB administration of tetrodotoxin. Histamine or the H2 receptor agonist dimaprit, applied directly to the hippocampus, failed to alter ACh release. Conversely, perfusion of MSA‐DB with these two compounds increased ACh release from the hippocampus. Also, thioperamide and ciproxifan, two H3 receptor antagonists, administered into MSA‐DB, increased the release of hippocampal ACh, whereas R‐α‐methylhistamine, an H3 receptor agonist, produced the opposite effect. The blockade of MSA‐DB H2 receptors, caused by local perfusion with the H2 receptor antagonist cimetidine, moderated the spontaneous release of hippocampal ACh and antagonized the facilitation produced by H3 receptor antagonists. Triprolidine, an H1 receptor antagonist, was without effect. Moreover, cells expressing c‐fos immunoreactivity were significantly more numerous in ciproxifan‐ or thioperamide‐treated rats than in controls, although no colocalization of anti‐c‐fos and anti‐ChAT immunoreactivity was observed. These results indicate a role for endogenous histamine in modulating the cholinergic tone in the hippocampus.