41 research outputs found

    Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia

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    金沢大学医薬保健研究域医学系Stress-induced analgesia (SIA) is a key component of the defensive behavioral "fight-or-flight" response. Although the neural substrates of SIA are incompletely understood, previous studies have implicated the hypocretin/orexin (Hcrt) and nociceptin/orphanin FQ (N/OFQ) peptidergic systems in the regulation of SIA. Using immunohistochemistry in brain tissue from wild-type mice, we identified N/OFQ-containing fibers forming synaptic contacts with Hcrt neurons at both the light and electron microscopic levels. Patch clamp recordings in GFP-tagged mouse Hcrt neurons revealed that N/OFQ hyperpolarized, decreased input resistance, and blocked the firing of action potentials in Hcrt neurons. N/OFQ postsynaptic effects were consistent with opening of a G protein-regulated inwardly rectifying K+ (GIRK) channel. N/OFQ also modulated presynaptic release of GABA and glutamate onto Hcrt neurons in mouse hypothalamic slices. Orexin/ataxin-3 mice, in which the Hcrt neurons degenerate, did not exhibit SIA, although analgesia was induced by i.c.v. administration of Hcrt-1. N/OFQ blocked SIA in wild-type mice, while coadministration of Hcrt-1 overcame N/OFQ inhibition of SIA. These results establish what is, to our knowledge, a novel interaction between the N/OFQ and Hcrt systems in which the corticotropin-releasing factor and N/OFQ systems coordinately modulate the Hcrt neurons to regulate SIA

    Ions modulate stress-induced nano-texture in supported fluid lipid bilayers.

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    Most plasma membranes comprise a large number of different molecules including lipids and proteins. In the standard fluid mosaic model, the membrane function is effected by proteins whereas lipids are largely passive and serve solely in the membrane cohesion. Here we show, using supported 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid bilayers in different saline solutions, that ions can locally induce ordering of the lipid molecules within the otherwise fluid bilayer when the latter is supported. This nanoordering exhibits a characteristic length scale of ∼20 nm, and manifests itself clearly when mechanical stress is applied to the membrane. Atomic force microscopy (AFM) measurements in aqueous solutions containing NaCl, KCl, CaCl2, and Tris buffer show that the magnitude of the effect is strongly ion-specific, with Ca2+ and Tris, respectively, promoting and reducing stress-induced nanotexturing of the membrane. The AFM results are complemented by fluorescence recovery after photobleaching experiments, which reveal an inverse correlation between the tendency for molecular nanoordering and the diffusion coefficient within the bilayer. Control AFM experiments on other lipids and at different temperatures support the hypothesis that the nanotexturing is induced by reversible, localized gel-like solidification of the membrane. These results suggest that supported fluid phospholipid bilayers are not homogenous at the nanoscale, but specific ions are able to locally alter molecular organization and mobility, and spatially modulate the membrane’s properties on a length scale of ∼20 nm. To illustrate this point, AFM was used to follow the adsorption of the membrane-penetrating antimicrobial peptide Temporin L in different solutions. The results confirm that the peptides do not absorb randomly, but follow the ion-induced spatial modulation of the membrane. Our results suggest that ionic effects have a significant impact for passively modulating the local properties of biological membranes, when in contact with a support such as the cytoskeleton

    Possible interpretations of the joint observations of UHECR arrival directions using data recorded at the Telescope Array and the Pierre Auger Observatory

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    Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia

    No full text
    Stress-induced analgesia (SIA) is a key component of the defensive behavioral “fight-or-flight” response. Although the neural substrates of SIA are incompletely understood, previous studies have implicated the hypocretin/orexin (Hcrt) and nociceptin/orphanin FQ (N/OFQ) peptidergic systems in the regulation of SIA. Using immunohistochemistry in brain tissue from wild-type mice, we identified N/OFQ-containing fibers forming synaptic contacts with Hcrt neurons at both the light and electron microscopic levels. Patch clamp recordings in GFP-tagged mouse Hcrt neurons revealed that N/OFQ hyperpolarized, decreased input resistance, and blocked the firing of action potentials in Hcrt neurons. N/OFQ postsynaptic effects were consistent with opening of a G protein–regulated inwardly rectifying K + (GIRK) channel. N/OFQ also modulated presynaptic release of GABA and glutamate onto Hcrt neurons in mouse hypothalamic slices. Orexin/ataxin-3 mice, in which the Hcrt neurons degenerate, did not exhibit SIA, although analgesia was induced by i.c.v. administration of Hcrt-1. N/OFQ blocked SIA in wild-type mice, while coadministration of Hcrt-1 overcame N/OFQ inhibition of SIA. These results establish what is, to our knowledge, a novel interaction between the N/OFQ and Hcrt systems in which the corticotropin-releasing factor and N/OFQ systems coordinately modulate the Hcrt neurons to regulate SIA

    Boundary Layer Transition on Slender Cones in Conventional and Low Disturbance Mach 6 Wind Tunnels

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    An experimental investigation was conducted on a 5-degree half-angle cone and a 5-degree half-angle flared cone in a conventional Mach 6 wind tunnel to examine the effects of facility noise on boundary layer transition. The influence of tunnel noise was inferred by comparing transition onset locations determined from the present test to that previously obtained in a Mach 6 low disturbance quiet tunnel. Together, the two sets of experiments are believed to represent the first direct comparison of transition onset between a conventional and a low disturbance wind tunnel using a common test model and transition detection technique. In the present conventional hypersonic tunnel experiment, separate measurements of heat transfer and adiabatic wall temperatures were obtained on the conical models at small angles of attack over a range of Reynolds numbers, which resulted in laminar, transitional, and turbulent flow . Smooth model turbulent heating distributions are compared to that obtained with transition forced via discrete surface roughness. The model nosetip radius was varied to examine the effects of bluntness on transition onset. Despite wall-to-total temperature differences between the transient heating measurements and the adiabatic wall temperature measurements, the two methods for determining sharp cone transition onset generally yielded equivalent locations. In the "noisy" mode of the hypersonic low disturbance tunnel, transition onset occurred earlier than that measured in the conventional hypersonic tunnel, suggesting higher levels of freestream acoustic radiation relative to the conventional tunnel. At comparable freestream conditions, the transition onset Reynolds number under low disturbance conditions was a factor of 1.3 greater than that measured on flared co..
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