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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 5-Aminoimidazole-4-carboxamide riboside (AICA riboside; Acadesine) activates AMP-activated protein kinase (AMPK) in intact cells, and is reported to exert protective effects in the mammalian CNS. In rat cerebrocortical brain slices, AMPK was activated by metabolic stress (ischaemia 〉 hypoxia 〉 aglycaemia) and AICA riboside (0.1–10 mm). Activation of AMPK by AICA riboside was greatly attenuated by inhibitors of equilibrative nucleoside transport. AICA riboside also depressed excitatory synaptic transmission in area CA1 of the rat hippocampus, which was prevented by an adenosine A1 receptor antagonist and reversed by application of adenosine deaminase. However, AICA riboside was neither a substrate for adenosine deaminase nor an agonist at adenosine receptors. We conclude that metabolic stress and AICA riboside both stimulate AMPK activity in mammalian brain, but that AICA riboside has an additional effect, i.e. competition with adenosine for uptake by the nucleoside transporter. This results in an increase in extracellular adenosine and subsequent activation of adenosine receptors. Neuroprotection by AICA riboside could be mediated by this mechanism as well as, or instead of, by AMPK activation. Caution should therefore be exercised in ascribing an effect of AICA riboside to AMPK activation, especially in systems where inhibition of adenosine re-uptake has physiological consequences.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 18 (2003), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The patterns and density of channels expressed in neurons critically determine their electrical properties. We have examined developmental regulation of Ca2+-channel expression during the maturation of the spinal motor circuits in Xenopus as it develops from an embryo to a larva. In embryonic neurons ≈ 60% of the current is carried by N-type channels, 8% by l-type channels and the remainder by an unidentified channel. As the embryo matures, ω-agatoxin-sensitive P/Q channels are gradually expressed and replace the unidentified HVA channel such that at stage 42 ≈ 25% of the current is carried by P/Q channels. We have used fluorescent labelling of selective channel toxins to directly observe the distribution of P/Q, N and BK channels. The P/Q channel distribution was most prevalent on the cell surface proximal to the areas of the soma where processes emerge. Both N and BK channels were distributed throughout the soma but still exhibited concentration around the areas adjacent to the emergence of processes from the soma. The patterns of fluorescence labelling during development mirrored the development of the respective ionic currents. Both N and P/Q channels contribute roughly equally to activation of the BK current, suggesting that overlap in the distribution of the N, P/Q and BK channels is important in their functional interdependence. The newly expressed P/Q channels play a role in spike initiation and repetitive firing in larval spinal neurons and contribute to burst generation during swimming in the larva.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 3 (1991), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A procedure for isolating spinal neurons of the Xenopus embryo has been devised. Using a variety of methods four of the eight previously described categories of neuron can be distinguished in vitro. Firstly, since many anatomical features of the neurons survived dissociation, sensory neurons and glycinergic inhibitory interneurons could be identified after isolation using anatomical criteria. Secondly, by selective labelling of the neurons in the intact spinal cord with fluorescein-conjugated dextran amines prior to dissociation, three classes of isolated neuron could be identified: motoneurons, putative excitatory interneurons and, once again, inhibitory interneurons. The identity of the inhibitory interneurons has been confirmed using glycine immunocytochemistry. The physiological properties of the isolated neurons were similar to those of their in vivo counterparts. The dissociated neurons exhibited strong membrane accommodation and outward rectification, both of which could be blocked by the injection of Cs+ ions. The neurons also retained their receptors for the agonists N-methyl-d-aspartate, kainate, quisqualate, glycine and GABA. Both the membrane properties and pharmacological sensitivity of the isolated neurons therefore appeared to be unaltered by the dissociation procedure. Thus the four classes of neuron from the Xenopus embryonic nervous system that can be identified after isolation constitute the basis for a valid model for detailed study of how the properties of individual neurons contribute to the functioning of the circuitry that underlies locomotor pattern generation in vertebrates.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 18 (2003), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The central pattern generator for swimming Xenopus embryo is organized as two half-centres linked by reciprocal inhibition. Microelectrode recordings suggest that Xenopus neurons are poorly excitable, necessitating a key role for postinhibitory rebound in the operation of the central pattern generator. However the Xenopus central pattern generator seems unusual in that the component neurons apparently have no intrinsic or conditional rhythmogenic properties. We have re-examined the firing properties of Xenopus embryo spinal neurons by making patch-clamp recordings in situ from intact spinal cord. Recordings made from 99 neurons were divided into three groups. Central pattern generator neurons overwhelmingly (44/51) fired trains of action potentials in response to current injection. Just over half of the sensory interneurons (13/22) also fired trains of action potentials. Neurons that received no synaptic inputs during swimming mostly fired just one or two action potentials (22/26). Thirty-four neurons were identified morphologically. Commissural (8/12) and descending (6/6) interneurons, key components of the spinal central pattern generator, fired repetitive trains of action potentials during current injection. Neurons that were not part of the central pattern generator did not demonstrate this preponderance for repetitive firing. Analysis of the interspike intervals during current injection revealed that the majority of central pattern generators, descending and commissural interneurons, could readily fire at frequencies up to twice that of swimming. We suggest that Xenopus neurons can be considered as conditional oscillators: in the presence of unpatterned excitation they exhibit an ability to fire rhythmically. This property makes the Xenopus embryonic central pattern generator more similar to other model central pattern generators than has hitherto been appreciated.
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 449 (2007), S. 1058-1062 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] A conserved network of eye field transcription factors (EFTFs) underlies the development of the eye in vertebrates and invertebrates. To direct eye development, Pax6, a key gene in this network, interacts with genes encoding other EFTFs such as Rx1 and Six3 (refs 4–6). ...
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 383 (1996), S. 259-263 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The actions of purinergic agonists and antagonists on the length of swimming episodes in the stage 37/38 Xenopus embryo were studied. The effects of ATP (10-100 \M) were variable, but there was overall a slight but significant reduction in the length of episodes (Fig. la, b). To eliminate any ...
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 436 (2005), S. 108-111 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Extracellular signalling by the purine nucleotide ATP has long been associated with sensory function. In the periphery, ATP mediates nociception, mechanosensitivity, thermal sensitivity and O2 chemosensitivity. These processes share a common mechanism that involves the release of ATP ...
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