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  • 2000-2004  (4)
  • 2002  (4)
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  • 2000-2004  (4)
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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 82 (2002), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Narp (neuronal activity regulated pentraxin) is a secreted immediate early gene product that is induced by synaptic activity. Recent studies have indicated that Narp may be an extracellular aggregating factor for AMPA receptors. Immunohistochemical studies have revealed prominent expression of Narp in the mossy fiber pathway of the dentate gyrus, suggesting it may be released pre-synaptically. However, invitro studies using recombinant Narp indicate that Narp may act when expressed by either pre- or post-synaptic elements. To help define Narp's mode of action, we have examined its localization in the habenula-interpeduncular pathway which also displays robust Narp expression. Focusing on this pathway as well as hippocampal and cortical Narp expression, we found prominent Narp staining in projection pathways and terminal fields. In contrast, Narp expression in dendrites was minimal in these neuronal populations. These findings indicate that, under physiological conditions, Narp is targeted to the synapse from pre- rather than post-synaptic elements. Our results also suggest that future studies focusing on these projection pathways that express high levels of Narp, in vivo, may help to understand the regulation and function of endogenous Narp.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 16 (2002), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recent in vitro studies demonstrated that Narp, a secreted immediate early gene (IEG) product, induces AMPA receptor clustering. Accordingly, Narp has been implicated in mediating activity-dependent changes in synaptic efficacy. To help define the role of Narp in vivo, we conducted immunohistochemical studies of Narp in rat brain. Unexpectedly, we found robust Narp expression in several discrete areas linked to the vestibular system: the anterodorsal nucleus (ADN) of the thalamus, which relays head orientation information to the cortex, the lateral vestibulospinal (Deiters′) nucleus and Purkinje cells in the flocculonodular lobe of the cerebellum. Although strong Narp expression in Deiters' nucleus and the cerebellum was present consistently, Narp expression in the ADN displayed a high degree of variability among animals. To check if this variability in ADN Narp expression reflects its dependence on fluctuating levels of vestibular input, we monitored Narp immunostaining following bilateral labyrinth ablation. This procedure significantly suppressed Narp immunostaining in the ADN, indicating that it is stimulated by naturally occurring vestibular input. In contrast, labyrinth ablation did not affect Narp staining in Deiters' nucleus or the flocculonodular lobe of the cerebellum, presumably because these areas are driven by inputs from multiple systems. As previous studies implicate Narp in synaptic plasticity, these findings suggest that this IEG may mediate ongoing adjustments in synaptic strength or connectivity in several pathways linked to the vestibular system.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 82 (2002), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recent studies have provided compelling evidence demonstrating that orexin (also known as hypocretin) neurons play a central role in the pathophysiology of narcolepsy. However, targeted deletion of orexin does not fully mimic the functional deficits induced by selective ablation of these neurons; implying that other secreted signaling molecules expressed in these neurons mediate key aspects of their function. In this study, we demonstrate that orexin neurons display robust expression of neuronal activity-regulated pentraxin (Narp), a secreted neuronal pentraxin, implicated in regulating clustering of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. Furthermore, we have found that hypothalamic melanin-concentrating hormone (MCH) neurons, which form a peptidergic pathway thought to oppose the effects of the orexin system, express another neuronal pentraxin, NP1. Thus, these findings suggest that these pathways utilize neuronal pentraxins, in addition to neuropeptides, as synaptic signaling molecules.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 83 (2002), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Translin is a nucleic acid binding protein that has been implicated in regulating the targeting and translation of dendritic RNA. In previous studies, we found that Translin and its partner protein, Trax, are components of a gel-shift complex that is highly enriched in brain extracts. In those studies, we employed a DNA oligonucleotide, GS1, as a probe to label the complex. Translin has also been identified as a component of a gel-shift complex detected using an RNA oligonucleotide probe, derived from the 3′ UTR of protamine-2 mRNA. Although we had assumed that these probes labeled the same complex, recent studies indicate that association of Trax with Translin suppresses its RNA binding activity. As these findings challenge this assumption and suggest that the native RNA binding complex does not contain Trax, we have re-examined this issue. We have found that the gel-shift complexes labeled with either GS1 or protamine-2 probes are ‘supershifted’ by addition of Trax antibodies, indicating that both are heteromeric Translin/Trax complexes. In addition, cross-competition studies provide additional evidence that these probes label the same complex. Furthermore, analysis of recombinant Translin/Trax complexes generated by co-transfection of Trax with Translin in hEK293T demonstrates that they are labeled with either probe. Although recombinant Translin forms a homomeric nucleic acid binding complex in vitro, our findings indicate that both Trax and Translin are components of the native gel-shift complex labeled with either GS1 or protamine-2 probes.
    Type of Medium: Electronic Resource
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