bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglia‐derived interleukin‐6 and leukaemia inhibitory factor promote astrocytic differentiation of neural stem/progenitor cells
Authors: Nakanishi Masaya , Niidome Tetsuhiro , Matsuda Satoru , Akaike Akinori , Kihara Takeshi , Sugimoto Hachiro 
Published: February 2007

AbstractNeural stem/progenitor cells (NSPCs) proliferate and differentiate depending on their intrinsic properties and local environment. It has been recognized that astrocytes promote neurogenic differentiation of NSPCs, suggesting the importance of cell–cell interactions between glial cells and NSPCs. Recent studies have demonstrated that microglia, one type of glial cells, play an important role in neurogenesis. However, little is known about how activated microglia control the proliferation and differentiation of NSPCs. In this study, we investigated the possibility that microglia‐derived soluble factors regulate the behaviour of NSPCs. To this end, NSPCs and microglial cultures were obtained from rat embryonic day 16 subventricular zone (SVZ) and rat postnatal 1 day cortex, respectively, and the conditioned medium from microglia was prepared. Microglial‐conditioned medium had no significant effect on the proliferation of NSPCs. In contrast, it increased the percentage of cells positive for a marker of astrocytes, glial fibrillary acidic protein (GFAP) during differentiation. The induction of astrocytic differentiation by microglial‐conditioned medium was reduced by the inhibition of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) and mitogen‐activated protein kinase (MAPK) pathways. Furthermore, microglia‐derived interleukin (IL)‐6 and leukaemia inhibitory factor (LIF) were identified as essential molecules for this astrocytic differentiation using neutralizing antibodies and recombinant cytokines. Our results suggest that microglia as well as astrocytes contribute to the integrity of the local environment of NSPCs, and at least IL‐6 and LIF released by activated microglia promote astrocytic differentiation of NSPCs via the activation of the JAK/STAT and MAPK pathways.
Impaired spatial working memory but spared spatial reference memory following functional loss of NMDA receptors in the dentate gyrus
Authors: Niewoehner B. , Single F. N. , Hvalby Ø. , Jensen V. , Meyer zum Alten Borgloh S. , Seeburg P. H. , Rawlins J. N. P. , Sprengel R. , Bannerman D. M. 
Published: February 2007

AbstractNovel spatially restricted genetic manipulations can be used to assess contributions made by synaptic plasticity to learning and memory, not just selectively within the hippocampus, but even within specific hippocampal subfields. Here we generated genetically modified mice (NR1ΔDG mice) exhibiting complete loss of the NR1 subunit of the N‐methyl‐d‐aspartate receptor specifically in the granule cells of the dentate gyrus. There was no evidence of any reduction in NR1 subunit levels in any of the other hippocampal subfields, or elsewhere in the brain. NR1ΔDG mice displayed severely impaired long‐term potentiation (LTP) in both medial and lateral perforant path inputs to the dentate gyrus, whereas LTP was unchanged in CA3‐to‐CA1 cell synapses in hippocampal slices. Behavioural assessment of NR1ΔDG mice revealed a spatial working memory impairment on a three‐from‐six radial arm maze task despite normal hippocampus‐dependent spatial reference memory acquisition and performance of the same task. This behavioural phenotype resembles that of NR1ΔCA3 mice but differs from that of NR1ΔCA1 mice which do show a spatial reference memory deficit, consistent with the idea of subfield‐specific contributions to hippocampal information processing. Furthermore, this pattern of selective functional loss and sparing is the same as previously observed with the global GluR‐A l‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazelopropionate receptor subunit knockout, a mutation which blocks the expression of hippocampal LTP. The present results show that dissociations between spatial working memory and spatial reference memory can be induced by disrupting synaptic plasticity specifically and exclusively within the dentate gyrus subfield of the hippocampal formation.
Doublecortin‐like, a microtubule‐associated protein expressed in radial glia, is crucial for neuronal precursor division and radial process stability
Authors: Vreugdenhil Erno , Kolk Sharon M. , Boekhoorn Karin , Fitzsimons Carlos P. , Schaaf Marcel , Schouten Theo , Sarabdjitsingh Angela , Sibug Rosana , Lucassen Paul J. 
Published: February 2007

AbstractDuring corticogenesis, progenitors divide within the ventricular zone where they rely on radial process extensions, formed by radial glial cell (RG) scaffolds, along which they migrate to the proper layers of the cerebral cortex. Although the microtubule‐associated proteins doublecortin (DCX) and doublecortin‐like kinase (DCLK) are critically involved in dynamic rearrangement of the cytoskeletal machinery that allow migration, little is known about their role in early corticogenesis. Here we have functionally characterized a mouse splice‐variant of DCLK, doublecortin‐like (DCL), exhibiting 73% amino acid sequence identity with DCX over its entire length. Unlike DCX, DCL is expressed from embryonic day 8 onwards throughout the early neuroepithelium. It is localized in mitotic cells, RGs and radial processes. DCL knockdown using siRNA in vitro induces spindle collapse in dividing neuroblastoma cells, whereas overexpression results in elongated and asymmetrical mitotic spindles. In vivo knockdown of the DCLK gene by in utero electroporation significantly reduced cell numbers in the inner proliferative zones and dramatically disrupted most radial processes. Our data emphasize the unique role of the DCLK gene in mitotic spindle integrity during early neurogenesis. In addition, they indicate crucial involvement of DCLK in RG proliferation and their radial process stability, a finding that has thus far not been attributed to DCX or DCLK.
EphA5 and ephrin‐A2 expression during optic nerve regeneration: a ‘two‐edged sword’
Authors: Symonds A. C. E. , King C. E. , Bartlett C. A. , Sauvé Y. , Lund R. D. , Beazley L. D. , Dunlop S. A. , Rodger J. 
Published: February 2007

AbstractDuring development, gradients of EphA receptors (nasallow–temporalhigh) and their ligands ephrin‐As (rostrallow–caudalhigh) are involved in establishing topography between retinal ganglion cells (RGCs) and the superior colliculus (SC). EphA5‐expressing RGC axons are repulsed by ephrin‐A2‐expressing SC neurones. In adult rats RGCs maintain graded EphA5 expression but ephrin‐A2 expression is down‐regulated in the SC to a weak gradient. At 1 month after optic nerve transection, EphA5 expression is reduced in the few remaining RGCs and is no longer graded; by contrast, SC ephrin‐A2 is up‐regulated to a rostrallow–caudalhigh gradient. Here we examined expression in adult rat 1 month after bridging the retina and SC with a peripheral nerve graft, a procedure that enhances RGC survival and permits RGC axon regeneration. Double labelling with cell markers revealed preservation of a nasallow–temporalhigh EphA5 gradient in RGCs and establishment of a rostrallow–caudalhigh ephrin‐A2 gradient within neurones of the SC. The results suggest a potential for guidance cues to restore the topography of RGC axons in the SC. However, high ephrin‐A2 levels were also found in astrocytes surrounding the peripheral nerve graft insertion site. The repulsive ephrin‐A2 environment offers at least a partial explanation for the observation that only a limited number of RGC axons can exit the graft to enter target central nervous system tissue.
Optimal sustained attention is linked to the spectral content of background EEG activity: greater ongoing tonic alpha (∼10 Hz) power supports successful phasic goal activation
Authors: Dockree Paul M. , Kelly Simon P. , Foxe John J. , Reilly Richard B. , Robertson Ian H. 
Published: February 2007

AbstractEfficient executive control frequently requires the timely activation or re‐activation of a task‐goal to enable purposeful behaviour. Additionally, more generalized factors such as alertness or neurological health will influence the efficiency with which control can be implemented. Goal‐directed processes have been investigated by examining event‐related potentials (ERPs), but much less is known about the involvement of background or ‘tonic’ processes reflected in the ongoing electroencephalogram (EEG), and how these affect the phasic processes expressed in the broad‐band ERP. Here, we investigate the relationship between a key attention‐sensitive tonic process – the alpha rhythm – and relevant phasic processes observed during a sustained attention paradigm in neurologically healthy subjects. We report that subjects with relatively higher tonic alpha power (∼10 Hz) show a larger‐amplitude late positive ERP component that is thought to index goal activation and has been found to predict good sustained attention performance as defined by correct response patterns. Source localization results suggest that the neural generators responsible for oscillatory alpha activity, which are found primarily in the parietal and occipital lobes, are distinct from those giving rise to the late positive component. The results are discussed in terms of increased alpha synchrony facilitating goal‐directed behaviour.
Contribution of NMDA receptor NR2B subunit to synaptic plasticity during associative learning in behaving rats
Authors: Valenzuela‐Harrington Mauricio , Gruart Agnès , Delgado‐García José M. 
Published: February 2007

AbstractThe difference in the amounts of NR2 subunits contained in NMDA receptors of the hippocampus has been related to their different involvement in activity‐dependent synaptic plasticity. Here, we show that Ro 25‐6981, a high‐affinity and selective blocker of NMDA receptors containing NR2B subunits, is able to block the acquisition of a trace conditioning paradigm in adult rats, a task that requires the active participation of hippocampal circuits. Reconditioning with the same trace paradigm was also prevented by Ro 25‐6981. In addition, we show that the slope of monosynaptic field excitatory postsynaptic potentials evoked at the dentate gyrus by single pulses presented to the medial perforant pathway increases significantly across conditioning sessions and during reconditioning, in a linear relationship with the increase in the number of classically conditioned eyelid responses. Administration of Ro 25‐6981 prevented these learning‐related changes in synaptic strength at the perforant pathway–dentate granule cell synapse. The present results suggest the involvement of NR2B‐containing NMDA receptors in hippocampal functions related to both associative learning and activity‐dependent synaptic plasticity.
Evaluation of transcranial magnetic stimulation for investigating transmission in descending motor tracts in the rat
Authors: Nielsen J. B. , Perez M. A. , Oudega M. , Enriquez‐Denton M. , Aimonetti J.‐M. 
Published: February 2007

AbstractIn the rat, non‐invasive transcranial magnetic stimulation (TMS) has shown promise for evaluation of transmission through the spinal cord before and after repair strategies, but it is still unclear which pathways are activated by TMS. The aim of the present study was therefore to identify these pathways and to analyse the effect of TMS on spinal neurons. In 19 rats, TMS evoked responses bilaterally in forelimb (biceps brachii; BB) and hindlimb muscles (tibialis anterior). The latency and amplitude of these motor‐evoked responses (MEPs) were highly variable and depended strongly on the coil position and the stimulation intensity. The most frequently observed latencies for the BB MEPs could be divided into three groups: 3–6 ms, 8–12 ms and 14–18 ms. Lesions in the dorsal columns, which destroyed the corticospinal tract at C2 and C5, significantly depressed MEPs in the mid‐ and high‐latency ranges, but not those in the low‐latency range. Lesions in the dorsolateral funiculus, which interrupted the rubrospinal tract, had no effect on MEPs in any of the latency ranges. By contrast, bilateral lesion of the reticulospinal tract and other ventro‐laterally located descending pathways abolished all responses. Intracellular recordings from 54 cervical motoneurons in five rats revealed that TMS evoked excitatory postsynaptic potentials (EPSPs) at latencies that corresponded well with those of the BB MEPs. The short‐latency EPSPs had rise times of around 1 ms, suggesting that they were mediated by a monosynaptic pathway. EPSPs with longer latencies had considerably longer rise times, which indicated conduction through polysynaptic pathways. Selective electrical stimulation of the pyramidal tract in the brainstem was performed in seven rats, where intracellular recordings from 70 motoneurons revealed that the earliest EPSPs and MEPs evoked by TMS were not mediated by the corticospinal tract, but by other descending motor pathways. Together, these results showed that in the rat TMS activates several descending pathways that converge on common spinal interneurons and motoneurons. Our observations confirm that the corticospinal tract has weak (and indirect) projections to cervical spinal motoneurons.
Diversity of GABAA receptor synaptic currents on individual pyramidal cortical neurons
Authors: Ing Timothy , Poulter Michael O. 
Published: February 2007

AbstractMiniature GABAA receptor‐mediated inhibitory postsynaptic currents (mIPSCs) in cortical pyramidal neurons have previously been categorized into two types: small amplitude mIPSCs with a mono‐exponential deactivation (mono‐mIPSCs) and relatively larger mIPSCs with bi‐exponential deactivation (bi‐mIPSCs). The aim of this study was to determine if the GABAA channels that underlie these mIPSCSs are molecularly distinct. We found, using non‐stationary noise analysis, that the difference in their amplitude could be not accounted for by their single channel conductance (both were 40 pS). Next, using α subunit selective GABAA receptor modulators, we examined the identity of the α subunits that may be expressed in the synapses that give rise to these mIPSCs. Zolpidem (100 and 500 nm, α1 selective) affected the deactivation of a subset of the mono‐mIPSCs, indicating that α1 subunits are not highly expressed in these synapses. However, zolpidem (100 nm) prolonged the deactivation of all bi‐mIPSCs, indicating a high abundance of α1 subunits in these synapses. SB‐205384 (α3 selective) had no effect on the mono‐mIPSCs but the bi‐mIPSCs were prolonged. Furosemide (α4 selective) reduced the amplitude of only the mono‐mIPSCs. L655,708 (α5 selective) reduced the amplitude of both populations and shortened the duration of the mono‐mIPSCs. Finally, we found that the neuroactive steroid pregesterone sulphate reduced the amplitude of both mIPSC types. These results provide pharmacological evidence that synapses on cortical pyramidal neurons are molecularly distinct. The purpose of these different types of synapses may be to provide different inhibitory timing patterns on these cells.
Inflammatory responses following Chlamydia pneumoniae infection of glial cells
Authors: Boelen E. , Steinbusch H. W. M. , Pronk I. , Grauls G. , Rennert P. , Bailly V. , Bruggeman C. A. , Stassen F. R. M. 
Published: February 2007

AbstractRecently, infections have been implicated in the pathogenesis of Alzheimer's disease. Apart from the direct effects of pathogens, it can be hypothesized that inflammatory mechanisms, such as the production of pro‐inflammatory mediators by resident glia, may result in neurotoxicity. Here, we examined the inflammatory responses in murine microglial cell (MMC) and murine astrocyte cell (MAC) lines following infection with Chlamydia pneumoniae (Cpn), a pathogen that has recently been associated with Alzheimer's disease. Furthermore, we determined whether these inflammatory responses are sufficient to cause neuronal cell death in vitro. MMCs and MACs were infected with Cpn. Subsequently, various chemo‐ and cytokines were determined in the culture supernatant fluid of infected/control cells at different time points post‐infection. Significantly higher levels of monocyte chemoattractant protein 1, interleukin (IL)‐6, tumour necrosis factor (TNF)‐α and IL‐1β were found in supernatant fluids of infected MMCs compared with controls. In contrast, in the supernatant fluid of infected MACs, only monocyte chemoattractant protein 1 and IL‐6 displayed significantly higher levels compared with controls. Moreover, neurotoxicity was examined up to 72 h after transferring the conditioned supernatant fluid to a neuronal cell layer. No neuronal cell death was observed when supernatant fluids from infected/mock‐treated MACs were transferred. However, when neurones were exposed to conditioned supernatant fluid from infected MMCs, a significant increase in cell death was observed compared with mock. Furthermore, adding neutralizing antibodies against IL‐6 and TNF‐α to that conditioned supernatant fluid prevented neuronal cell death by ∼50%. In conclusion, these data suggest that Cpn infection results in a pro‐inflammatory milieu, particularly by activating MMCs, that ultimately results in neurodegeneration with prominent roles for both IL‐6 and TNF‐α.
Pollination and other ecosystem services produced by mobile organisms: a conceptual framework for the effects of land‐use change
Authors: Kremen Claire , Williams Neal M. , Aizen Marcelo A. , Gemmill‐Herren Barbara , LeBuhn Gretchen , Minckley Robert , Packer Laurence , Potts Simon G. , Roulston T'ai , Steffan‐Dewenter Ingolf , Vázquez Diego P. , Winfree Rachael , Adams Laurie , Crone Elizabeth E. , Greenleaf Sarah S. , Keitt Timothy H. , Klein Alexandra‐Maria , Regetz James , Ricketts Taylor H. 
Published: February 2007

AbstractMany ecosystem services are delivered by organisms that depend on habitats that are segregated spatially or temporally from the location where services are provided. Management of mobile organisms contributing to ecosystem services requires consideration not only of the local scale where services are delivered, but also the distribution of resources at the landscape scale, and the foraging ranges and dispersal movements of the mobile agents. We develop a conceptual model for exploring how one suchmobile‐agent‐based ecosystem service(MABES), pollination, is affected by land‐use change, and then generalize the model to other MABES. The model includes interactions and feedbacks among policies affecting land use, market forces and the biology of the organisms involved. Animal‐mediated pollination contributes to the production of goods of value to humans such as crops; it also bolsters reproduction of wild plants on which other services or service‐providing organisms depend. About one‐third of crop production depends on animal pollinators, while 60–90% of plant species require an animal pollinator. The sensitivity of mobile organisms to ecological factors that operate across spatial scales makes the services provided by a given community of mobile agents highly contextual. Services vary, depending on the spatial and temporal distribution of resources surrounding the site, and on biotic interactions occurring locally, such as competition among pollinators for resources, and among plants for pollinators. The value of the resulting goods or services may feed back via market‐based forces to influence land‐use policies, which in turn influence land management practices that alter local habitat conditions and landscape structure. Developing conceptual models for MABES aids in identifying knowledge gaps, determining research priorities, and targeting interventions that can be applied in an adaptive management context.
High local and global diversity of Flavobacteria in marine plankton
Authors: Alonso Cecilia , Warnecke Falk , Amann Rudolf , Pernthaler Jakob 
Published: February 2007

SummaryMembers of the phylum Bacteroidetes are among the most abundant microbes in coastal marine waters, but it is unclear to which extent the diversity within this phylum is covered by currently available 16S rRNA gene sequence information. We, thus, obtained a comprehensive collection of sequence types affiliated with Bacteroidetes in coastal North Sea surface waters and we compared this local diversity with the available sequences of marine planktonic and other aquatic Bacteroidetes. Approximately 15% of > 600 clones from two libraries (August 2000, June 2001) were related to Bacteroidetes, specifically to the Flavobacteria. Local diversity appeared to be almost exhaustively sampled. However, the diversity of the two libraries virtually did not overlap, indicating a pronounced temporal variability of the planktonic Flavobacteria assemblage. The majority of sequence types represented novel phylogenetic lineages, adding 6–7% to the currently known genera and species of Bacteroidetes in marine waters. Different diversity estimators suggested that so far only approximately half of the global diversity of planktonic marine Bacteroidetes has been described. The data set moreover indicated that cultivation‐independent techniques and isolation approaches have recovered almost equally sized and virtually non‐overlapping fractions of the currently known diversity within this phylum. Interestingly, only 15% of genera of Bacteroidetes from various aquatic environments appear to occur in more than one habitat type.
Hydrogen ‘leakage’ during methanogenesis from methanol and methylamine: implications for anaerobic carbon degradation pathways in aquatic sediments
Authors: Finke Niko , Hoehler Tori Michael , Jørgensen Bo Barker 
Published: February 2007

SummaryThe effect of variations in H2 concentrations on methanogenesis from the non‐competitive substrates methanol and methylamine (used by methanogens but not by sulfate reducers) was investigated in methanogenic marine sediments. Imposed variations in sulfate concentration and temperature were used to drive systematic variations in pore water H2 concentrations. Specifically, increasing sulfate concentrations and decreasing temperatures both resulted in decreasing H2 concentrations. The ratio of CO2 and CH4 produced from 14C‐labelled methylamine and methanol showed a direct correlation with the H2 concentration, independent of the treatment, with lower H2 concentrations resulting in a shift towards CO2. We conclude that this correlation is driven by production of H2 by methylotrophic methanogens, followed by loss to the environment with a magnitude dependent on the extracellular H2 concentrations maintained by hydrogenotrophic methanogens (in the case of the temperature experiment) or sulfate reducers (in the case of the sulfate experiment). Under sulfate‐free conditions, the loss of reducing power as H2 flux out of the cell represents a loss of energy for the methylotrophic methanogens while, in the presence of sulfate, it results in a favourable free energy yield. Thus, hydrogen leakage might conceivably be beneficial for methanogens in marine sediments dominated by sulfate reduction. In low‐sulfate systems such as methanogenic marine or freshwater sediments it is clearly detrimental – an adverse consequence of possessing a hydrogenase that is subject to externally imposed control by pore water H2 concentrations. H2 leakage in methanogens may explain the apparent exclusion of acetoclastic methanogenesis in sediments dominated by sulfate reduction.